Manual on the Prevention and Control of Common Cancers WHO REGIONAL PUBLICATIONS • 20 WESTERN PACIFIC SERIES NO.
Western Pacific Region Règion du Pacific occidental
Cataloguing in Publication Data Manual on the prevention and control of common cancers WHO Regional Publications, Western Pacific Series, No. 20 1. Neoplasms - prevention and control. 2. Neoplasms - epidemiology. 3. National Health Programmes. I. Series 3. Neoplasms - therapy. 4. Manuals. 6. Western Pacific.
ISBN 92 9061 118 9
(NLM Classification: QZ 200)
The World Health Organization welcomes requests for permission to reproduce or translate its publications, in part or in full. Applications and enquiries should be addressed to the Office of Publications, World Health Organization, Geneva, Switzerland or to the Regional Office for the Western Pacific, Manila, Philippines which will be glad to provide the latest information on any changes made to the text, plans for new editions, and reprints and translations already available. © World Health Organization 1998 Publications of the World Health Organization enjoy copyright protection in accordance with the provisions of Protocol 2 of the Universal Copyright Convention. All rights reserved. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.
Table of Contents Preface Acknowledgements Introduction 1. Cancer in the Western Pacific Region 2. National cancer control programmes 3. Cancer surveillance 4. Tobacco or health 5. Diet, nutrition and the prevention of chronic diseases 6. Health education 7. Cancer pain relief and palliative care 8. Oral cancer 9. Nasopharhyngeal cancer 10. Oesophageal cancer 11. Stomach cancer 12. Colonic and rectal cancer 13. Liver cancer 14. Lung cancer 15. Skin cancer 16. Breast cancer 17. Cervical cancer Glossary Appendices v vii ix 1 8 32 44 77 94 125 176 189 195 202 209 217 225 239 251 270 291 295
Acknowledgements T he Western Pacific Regional Office of the World Health Organization acknowledges the valuable contribution made to this manual by the following: Contributors: Dr E. R. Cortez, Philippine Academy for Head and Neck Surgery, Metro Manila Dr A.S. de la Peña, Philippine College of Surgeons, Metro Manila Dr A. V. Laudico, Surgical Oncology Society of the Philippines, Metro Manila (Group Leader) Dr A. M. Manalo, Society of Gynecologic Oncologists of the Philippines, Metro Manila Dr D.M. Parkin, International Agency for Research on Cancer, Lyon, France Dr D. Tan, Antismoking Coalition of the Philippines, Metro Manila Dr S. Tempongco, College of Public Health, University of the PhilippinesManila
Reviewers: Dr U. Gatzemeir, Hospital Grobhandsclorf, Grobhansclorf, Germany Dr A. Green, Queensland Institute of Medical Research, Queensland, Australia Dr P.C. Gupta, Tata Institute of Fundamental Research, Bombay, India Dr N. MacDonald, Clinical Research Institute of Montreal, Quebec, Canada Dr J. Mackay, Asian Consultancy on Tobacco Control, Kowloon, Hong Kong Dr K. Maruyama, National Cancer Center Hospital, Tokyo, Japan Dr A.B. Miller, Faculty of Medicine, University of Toronto, Ontario, Canada Dr R.M. Nambiar, Singapore Cancer Society, Singapore Dr E. Riboli, International Agency for Research on Cancer, Lyon, France Dr De Sheng Wan, Sun Yat Sen University of Medical Sciences, Guangzhou, People’s Republic of China
- vii -
Acknowledgements
Dr Zhao Yu Tang, Shanghai First Medical University, Shanghai, People's Republic of China
The members of the Working Group on Cancer Prevention and Control convened by the WHO Regional Office for the Western Pacific in Manila, 7-11 October 1996: Dr Yoon-OK Ahn, Seoul National University College of Medicine, Seoul, Republic of Korea Dr B. Cox, University of Otago, Dunedin, New Zealand Dr M. Dorsch (Chairman), National Centre for Disease Control, Commonwealth Department of Health and Family Services, Canberra, Australia Dr Yu Tang Gao (Vice Chairman), Shanghai Cancer Institute, Shanghai, People’s Republic of China Professor A.J. Hedley, The University of Hong Kong, Hong Kong Dr Ng Kok Han, Institute for Medical Research, Kuala Lumpur, Malaysia Professor S. Sato, Kobe University School of Medicine, Kobe, Japan Dr F. Takeda, Saitama Cancer Centre, Saitama, Japan Dr Patrick Tan (Rapporteur), Singapore General Hospital, Singapore Dr Guang Wei Xu, Beijing Institute for Cancer Research, Beijing, People’s Republic of China Dr R. Maclennan (Consultant), Queensland Institute of Medical Research, Brisbane, Australia Dr A.V. Laudico (Consultant), Philippine College of Surgeons , Metro Manila, Philippines Dr D.M. Parkin (Secretariat), International Agency for Research on Cancer, Lyon, France Dr Han Tieru (Secretariat), WHO-Regional Office for the Western Pacific, Manila
- viii-
Preface C ancer is widely recognized as one of the most formidable human afflictions. It is an increasingly important item on every country’s health agenda. Cancer annually affects 10 million people and causes 6 million deaths worldwide. In the Western Pacific Region, cancer is one of the five leading causes of adult mortality in 26 countries and areas. In China alone, deaths from cancer amount to 1.3 million each year. As the proportion of elderly people is increasing in most countries, so too are tobacco use, unhealthy behaviours, and exposure to other carcinogens. The burden of cancer is therefore likely to rise significantly. It is expected that 300 million new cases of cancer and 200 million deaths from the disease will occur globally in the next 25 years, with almost two-thirds of cases arising in developing countries. Scientific studies and successful control activities indicate that cancer is not inevitable. One-third of all cancer cases are preventable, and further one-third are potentially curable if diagnosed sufficiently early, while appropriate palliative care of the remaining one-third of cancer patients can bring about substantial improvement in the quality of life. The world today provides many challenges to our traditional ways. Many new health issues have appeared which require different approaches. Individuals, the family and the community have more responsibility than ever before to help themselves avoid diseases and to develop lifestyles and environments that support positive health. Governments must ensure that appropriate policies are developed and adequate services are in place to support individual, family and community activities. Cancer prevention and control must take into account the larger context in which people live and work, which helps to shape their health. Innovative approaches which are people-centred and reflect the recognition that lives are led in complex and changing circumstances, are proposed in the regional policy framework, New horizons in health which was endorsed by the Member States at the forty-fifth session of the Regional Committee in 1994.
Health promotion is an important approach. Through health promotion, we can encourage people, in conjunction with their families,
-v-
Preface
communities and nations, to improve and manage their own health. Most of the measures for primary prevention and early detection of cancer are strongly related to personal behaviours and lifestyles, as well as to awareness of health issues. Therefore, the general public should be provided with sufficient information and guidance on what are risk factors and how to avoid them. They need to know what may cause cancers, how to prevent some types of cancers, and how to recognize early signs of cancer. Development and implementation of cancer control programmes should be intensified at national, provincial and community levels with emphasis on tobacco control activities; promotion of a healthy diet; infant vaccination against Hepatitis B; an increase in the coverage of early detection and screening for breast cancer and cervical cancer; and availability of palliative care, especially the WHO method on pain relief, in all countries of the Region. The importance of integrating cancer control into primary health care should be emphasized. This is a direct response to the epidemiological transition of disease patterns occurring in many countries and areas. Primary health care workers, community health educators, family doctors and nurses should play an important role in cancer control. Their knowledge, attitudes and practices need to be upgraded with regard to the scientific evidence supporting cancer causation and primary prevention, durability of certain cancers when these are detected early, and the successful amelioration of suffering through cancer palliative care and pain relief. This manual presents current knowledge on prevention and control of common cancers and defines the tasks wherein health workers will be most useful. By doing so, it is hoped that attitudes will also change, from a sense of pessimism and hopelessness, to a firm conviction that indeed cancer can be prevented and controlled, and that cancer control can be enhanced at grassroots level through an improvement in knowledge, skills in prevention and early detection, and palliative care.
S. T. Han, MD, Ph.D. Regional Director
- vi -
Introduction T he cancer control programme review conducted in l994 by the WHO Western Pacific Regional Office suggested that the current objectives, targets and strategies for cancer control were too general. Specific packages for each type of common cancer should be developed, offering the most effective intervention measures. In order to respond to this suggestion, the development of a manual on the prevention and control of common cancers was proposed. The manual was to serve several purposes, namely: 1) to provide detailed guidance on WHO strategies for the prevention and control of common cancers; 2) to provide an update on the epidemiological situation and the epidemiological characteristics of common cancers which are prevalent in the region; 3) to provide standardized intervention methods for primary prevention, early detection and curative treatment, in addition to cancer pain relief and palliative care, and to provide evaluations of the intervention methods for different common cancers in terms of scientific views on their effectiveness, acceptability and prognosis; 4) to collaborate with Member States and health professionals in establishing targets, setting priorities and explaining intervention methods for prevention and control of common cancers; and 5) to provide scientific information on the prevention and control of common cancers to be used in health education for the general public and health campaigns in member countries.
-ix -
Introduction
The manual was to be developed especially for primary health care workers, general practitioners and nurses in district health units, township or community health centres, and public health educators in the prevention and control of cancers. It was to be used as a guide or reference to: 1) provide WHO strategies and standardized approaches on the prevention and control of common cancers; 2) develop local or national programmes on prevention, early detection and curative treatment, and cancer pain relief and palliative care of common cancers; 3) develop training materials for health workers who are dealing with prevention, early detection and palliative care at the grassroots level; 4) develop health education materials and programmes to prevent and control common cancers; and 5) evaluate cancer intervention measures including primary prevention, early detection and screening, and cancer pain relief based on effectiveness, acceptability and costeffectiveness. It was assumed that, firstly, a large number of health workers themselves are still unaware or unconvinced that many cancers can either be prevented or cured when detected early. In addition, many still do not fully realize that much of the pain and suffering of advanced cancer can be effectively relieved. The following misconceptions appeared to be fairly prevalent: • • • We still do not know what causes cancer. (So how can we prevent it?) Cancer is incurable (So why bother with early detection?) Suffering is inevitable with cancer. (So why bother consenting to treatment, or even to consult a physician?)
Secondly, it appeared that those who are beginning to believe that something can be done hesitate to actively participate, thinking their individual efforts futile and unaware of the other elements of the total cancer prevention and control programme. Thirdly, it was assumed
-x-
Manual on the prevention and control of common cancers
•
The health worker should work with different sectors who can provide support (logistical, medical and other types). The experience should be made as pleasant as possible, especially to initial adoptors, to prevent a negative campaign against the programme. Follow-up activities should be planned to ensure the participation of hard-to-reach groups. Results of screening programmes should be provided and explained to participants as soon as possible.
•
•
•
-124-
Health education
References and suggested readings 1. 2. 3. 4. Control of oral cancer in developing countries. Bulletin of the World Health Organization, 1984, 62 (6): 817-830. Green, L., M. Kreuter, eds. Health promotion planning: an educational and environmental approach, 2nd edition. Mayfield Publishing Company, 1991. Tomatis, L. (ed.) Cancer: causes, occurrence and control. Lyon, International Agency for Research on Cancer, 1990 (IARC Scientific Publications, No. 100). US Department of Health and Human Services. Making health communication work . Office of Cancer Communication, 1992 (NIH Publication No. 92-1493). Use of quantitative methods in planning national cancer control programme. Bulletin of the World Health Organization, 1986, 64(5):683-693.
5.
-125-
7.
Cancer pain relief and palliative care Introduction
T
he number of cancer patients worldwide is increasing. Of the estimated ten million new cancer cases every year, more than half are in developing countries. The disease is incurable for the majority of these patients by the time it is diagnosed. Medical care is a continuum, ranging from complete cure at one end to emphasis on symptom control at the other. Hence, a major decision in the treatment of cancer patients is determining whether the aim of the therapy is curative or palliative. Cure in cancer does not imply the total eradication of cancer cells in the patient, but rather the occurrence, following treatment, of a reasonably long period when the patient is clinically free from cancer. Cure rate may be expressed as the probability of patients attaining a disease-free state for a certain number of years, usually five or ten, following treatment. When a great majority of patients survive the predetermined number of years following a specific interventional treatment, it is considered curative. To illustrate, 80-90 per cent of women who have breast cancer with a tumour diameter of less than 2 cm and whose ipsilateral axillary nodes do not contain metastasis are expected to be alive ten years after undergoing a modified radical mastectomy or a tumourectomy with therapeutic breast and axillary irradiation. This particular stage of breast cancer is thus curable with these curative interventions. While a small proportion of
Manual on the prevention and control of common cancers
women in this subset of patients will die of breast cancer within ten years, this does not detract from the curability. On the other hand, less than a third of women with locally advanced breast cancer are expected to live five years after any kind of interventional treatment, singly or in combination, and many less after ten years. Thus, in this set of patients, the therapeutic aim is to palliate, and not to cure, even if for some reason or another a few women do survive for long periods of time. Therefore, it is the known probability of surviving within a determined period that determines curability or non-curability. Palliative care, on the other hand, is the active total care of patients whose disease is no longer responsive to curative treatment. The goal of palliative care is achievement of the best possible quality of life for patients and their families. Control of pain and of other symptoms, and alleviation of psychological, social and spiritual problems are paramount. Palliative care affirms life and regards dying as a normal process; neither hastens nor postpones death; provides relief from pain and other distressing symptoms; integrates the psychological and spiritual aspects of patient care; offers a support system to help patients live as actively as possible until d eath; and offers a support system to help the family cope during the patient's illness and in their own bereavement.
Cancer pain relief A major requirement of palliative cancer care is cancer pain relief. Many types of primary cancer therapy span the entire spectrum of care, notably radiotherapy, and to a lesser extent chemotherapy and surgery. Such techniques as well as pharmacological and non-pharmacological interventions can provide adequate relief to the vast majority of patients (Table 7.1). In palliative care, symptom control should be as complete and as long as possible. Optimizing the quality of life for the patient and the family requires integrating the physical, psychological and spiritual aspects of patient care, and taking into account the prevailing local, social, cultural, and economic realities and their implications.
-126-
Cancer pain relief and palliative care
Table 7.1. Roles of the primary therapies in the management of cancer pain (Reference 1). Primary therapy Radiotherapy Major pain indications painful bony metastases, epidural spinal cord compression, cerebral metastases, tumour-related compression or infiltration of peripheral neural structures nociceptive or neuropathic pain syndromes caused by tumours likely to respond to chemotherapy stabilization of pathological fractures, spinal cord decompression, relief of remediable bowel obstructions, drainage of symptomatic ascites Overt infections (eg. pelvic abscess, pyonephrosis), occult infections (e.g. in head and neck tumours or ulcerating tumours)
Chemotherapy Surgery Antibiotic therapy
It is important to keep the therapeutic aim clearly in mind when employing treatment of any kind. The aim of palliative surgery, for example, is the rapid, efficient, and long-lasting relief of symptoms due to locoregional disease. Like surgery, radiotherapy is directed at locoregional disease. The relief of pain due to localized bone metastasis is an indication for palliative radiotherapy. Systemic therapies include chemotherapy, hormone therapy and immunotherapy. Their indications are shown in Table 7.2. The WHO Essential Drug List of Antineoplastic and Immunosuppressant drugs is shown in Appendix 2 . They, however, infrequently result in immediate relief of symptoms. Successful pain management is characterized by the implementation of the techniques with the most favourable therapeutic index for the prevailing circumstances and a continuity of care that responds quickly to the changing needs of the patient. The key points to bear in mind are: (1) the patient's biological prospects; (2) the therapeutic aim of each treatment; (3) the unwanted effects of treatment; (4) the benefits of treatment for the patient; and (5) the need not to prescribe a lingering death. The philosophy of palliative cancer care stresses that illness should not be regarded as an isolated aberration in physiology, but considered in terms of the suffering that it causes. While unrelieved cancer pain may be the greatest factor causing distress to patients, the relief of pain by itself does not necessarily bring about an acceptable quality of life.
-127-
Manual on the prevention and control of common cancers
Table 7.2. Capabilities of systemic anticancer therapy; a summary of situations (Reference 7). Capability Cure achievable in >50 per cent of patients despite wide-spread metastases Situation Testis cancer Gestational trophoblastic disease Non-Hodgkin's lymphomas (NHL) with unfavorable histology Hodgkin's disease Childhood acute lymphocytic leukemia (ALL) Breast cancer Colorectal cancer Wilm's tumor Neuroblastoma Osteosarcoma Ewing's sarcoma Ovarian cancer Breast cancer Acute myeloid leukemia (AML) "Favorable histology" NHL Small cell lung cancer (SCLC) Prostate cancer Renal cell cancer Bladder cancer
Increased cure rate augmented when systemic therapy is added to definitive local therapy
Definite tumour mass reduction in disseminated disease, complete remission and unequivocal palliation achievable, cure not possible or infrequent (<20 per cent)
This table is meant to be simply illustrative of human tumours in which systemic therapy is definitely useful. By inference, systemic therapy with currently available agents offers little major benefit in tumors not listed. (e.g., advanced colorectal cancer, soft-tissue sarcomas, non-small cell lung cancer, gastric, pancreatic, hepatocellular, cervical, and nasopharyngeal carcinoma).
The pain that a patient suffers has impact on the family, making the "unit of care" the family rather than the patient alone. This setting is regarded as most important. For this reason, inquiries from the family are encouraged and the family's active participation in the care is expected. Ideal home care requires constancy of care between home and hospital. Members of the family should therefore be trained to select and prepare a suitable way of life for the cancer patient. Whereas acute pain experienced by cancer patients is usually related to diagnostic and therapeutic interventions, chronic cancer pain is most commonly caused by direct tumour infiltration. Cancer patients need pain relief at all stages of their disease. Severe, unrelenting pain without the hope of relief is incompatible with an acceptable quality of life. It interferes with the ability to eat, sleep, think,
-128-
Cancer pain relief and palliative care
and interact with others. The aim of treatment is to relieve the pain to the patient's satisfaction as soon as possible so that he or she can function effectively and eventually die free of pain, if death is imminent. Quality of life enhancement and cancer pain relief is applicable to all patients and not only to the terminally ill. A large number of patients with advanced incurable cancer are in fact not terminally ill and can still live meaningful and productive lives if their pain is relieved. There are simple and inexpensive methods that can provide relief to the majority of patients suffering from cancer pain. Table 7.3 presents the strategy for the management of cancer pain. Table 7.3. Strategy for management of cancer pain (Reference 1). 1) 2) Comprehensive assessment Primary therapy and systemic non-opioid and opioid analgesic therapy a) b) c) Role of primary therapies Selection of non-opioid and opioid analgesic agents Practical aspects of administration: * routes * dose selection and titration Management of side effects
d)
3) Non-invasive intervention for patients unable to attain an acceptable balance between relief and side effects of systemic opioid therapy a) Reduce opioid requirement by * appropriate primary therapy * addition of non-opioid analgesic * addition of an adjuvant analgesic * use of cognitive or behavioural techniques * use of an orthotic device or other physical medicine approach Switch to another opioid
b) 4) relief
Invasive interventions for patients unable to attain acceptable balance between and side effects during systemic pharmacotherapy a) b) c) Regional analgesic techniques (spinal and intraventricular opioids) Neural blockade Neuroablative techniques
-129-
Manual on the prevention and control of common cancers
5) other
Use of sedation to manage intractable pain for patients who fail to benefit from therapeutic options
-130-
Cancer pain relief and palliative care
The main features of a cancer pain relief and palliative care programme are summarized diagrammatically in Figure 7.1.
Figure 7.1. Relieving cancer pain
Implementation Tailor treatment policy to predominant pattern of malignant diseases and available resources Identify patient groups suitable only for palliative therapy Establish national committee on guidelines for palliative care specific to cancer site Set up a threefold strategy based on the following:
Education Of the public Of health care professionals (doctors, nurses, pharmacists) Of others (health care policy-makers, administrators, drug regulators
Drug Availability Changes in health care regulations/ legislation to improve drug availability (especially of opioids) Improvements in prescribing distributing, dispensing, and administration of drugs
Government policy National or state policy emphasizing the need to alleviate chronic cancer pain
Process measures >80% of cancer specialists instructed in the guidelines for cancer pain relief >50% of general physicians informed about cancer pain relief guidelines >50% of cancer patients and their relatives informed that relief of cancer pain is possible Impact measures Oral morphine available for use in primary health care >80% of cancer hospitals have adopted WHO cancer pain relief guidelines >50% of general hospitals have adopted WHO cancer pain relief guidelines Outcome measures Short term: >50% of patients with cancer pain receive oral morphine Medium term: >30% of cancer patients freed from peak cancer pain Long term: >80% of cancer patients freed from peak cancer pain
Source: National Cancer Control Programmes. Geneva, WHO, 1996.
-131-
Manual on the prevention and control of common cancers
Cancer Pain Assessment Assessment or evaluation of pain is the first step in cancer pain management. The main steps in the evaluation of cancer pain include the following: 1. 2. Believe the patient's report of pain. Initiate discussions about pain. The health worker should specifically ask the patient about pain rather than rely on spontaneous comment. To help assess the severity of pain, inquire about observations of care-givers, vocalizations (like groaning), facial expressions (like furrowed eyebrows), changes in physiological responses (like increase or decrease in blood pressure), and response to a trial dose of analgesic. Evaluate the severity of pain. The health worker should find out whether activity is limited by the pain, whether sleep and appetite are disturbed, and the degree of relief obtained with medication or painrelief procedures in the past and at present. Numerical scales for pain are easy to improvise and are helpful in adults. The Brief Pain Inventory (BPI) of the Pain Research Group has shown consistent cross-cultural validation between the intensity of pain and the impairment of certain aspects of quality of life. For both children and adults, it is often helpful to offer a choice of descriptors (e.g. pressure, aching, burning, stabbing) and to ask the patient to relate the present pain to past pain, such as toothache. Young children may be able to convey the intensity of their pain by using a set of drawings of faces ranging from smiling to crying, and selecting the face that best matches the pain. Alternatively, the child may be presented with four coins or pebbles and asked to indicate how many "pieces of hurt" are felt, with the four objects indicating the worst pain. A similar approach can be used with patients who cannot read or write and where communication is difficult because of the lack of a common language. Take a detailed history of pain. Discover the pain’s characteristics such as its intensity, quality, location and distribution. It is also important to determine whether it is continuous or intermittent and what factors make it worse or better. Evaluate the psychological state of the patient. While overt pain behaviour may be absent, it may be associated with psychological disturbance. Depression occurs in 25 per cent of cancer patients. The
3.
4.
5.
-132-
Cancer pain relief and palliative care
diagnosis of manageable depression and/or anxiety is often missed in patients with advanced cancer. 6. 7. Perform a careful physical examination. Order and personally review any necessary investigation. Investigations should be reserved for cases where there is doubt about the cause of pain, or where a decision about further anticancer treatment depends on the precise localization of the disease. Nevertheless, analgesics should not be withheld while the cause of the pain is being established. Consider alternative methods of pain control. Alternative methods are of considerable benefit for some forms of cancer. Monitor the results of treatment. Physicians and other caregivers must establish regular and specific methods for sharing information about the effects of the treatment so that, when necessary, changes in treatment can be made quickly.
8. 9.
Evaluation should enable the clinician to appreciate the precise nature of the pain syndrome, its impact, and concurrent symptoms and problems that further undermine the quality of life. After the evaluation of pain, the physician should know whether the pain is caused by the cancer or by another disorder, constitutes a specific cancer pain syndrome, its mechanism, whether it is associated with a significant degree of psychological distress, or is having a negative impact on the patient's family and/or care-givers.
Systemic analgesic therapy The individual practitioner can effectively treat the majority of pain problems by attending to careful pain assessment and implementing analgesic therapy. The basic drug list recommended by WHO is shown in Table 7.4.
-133-
Manual on the prevention and control of common cancers
Table 7.4. A basic drug list for cancer pain relief (Reference 9) Category Non-opioids Basic drugs acetylsalicylic acid (ASA) paracetamol ibuprofen indomethacin codeine b Alternatives choline magnesium trisalicylate diflunisal naproxen diclofenac dihydrocodeine dextropropoxyphene standardized opium tramadol methadone hydromorphone oxycodone c levorphanol pethidine buprenorphine c
Opioids for mild to moderate pain a Opioids for moderate to severe pain a
morphine
Opioid antagonist Antidepressants Anticonvulsants Corticosteroids a d d
naloxone amitriptyline carbamazepine e
imipramine valproic acid prednisone betamethasone
prednisolone dexamethasone
For practical purposes, the opioids are divided into those for mild to moderate pain those for moderate to severe pain, principally on the grounds of common patterns
and of b
use. Codeine and some other opioids for mild to moderate pain are not scheduled drugs most countries. This may make them more easily available. Buprenorphine is a partial agonist (i.e. it has a pharmacological ceiling). At low
in c
doses (0.2 mg every 8 hours), it is an alternative to codeine. At higher doses (up to 1 mg every 8 hours), it is equivalent to about 30 mg of oral morphine every 4 hours. d Antidepressants and anticonvulsants are the drugs of choice for neuropathic pain. e Of value in nerve compression and spinal cord compression pain, also for headache due to raised intracranial pressure. May be used as an alternative to, or in conjunction with a non-steroidal anti-inflammatory drug (NSAID) for bone pain. If used with an NSAID, there is an increased likelihood of adverse gastric effects and of fluid retention.
-134-
Cancer pain relief and palliative care
Drug treatment is the mainstay of cancer pain management. The WHO three-step analgesic ladder approach to systemic pharmacotherapy guides the care-giver in dealing with the different levels of pain the patient experiences: (Figure 7.2)
Figure 7.2. The three-step analgesic ladder
-135-
Manual on the prevention and control of common cancers
1.
Patients with mild to moderate cancer-related pain should be treated with a non-opioid analgesic (Table 7.5), which should be combined with an adjuvant analgesic if a specific indication for one exists. Table 7.5. Non-opioid analgesics (Reference 4) Chemical class Generic Name Halflife (hours ) 3-4 Starting (mg) Max. dose (mg/day)
Non-acidic P-aminophenol derivatives Acidic salicylates
Paracetamol
50 q4h
6000
aspirin salsalate
3-4 -12 3-4 1-3 2-3 5-6 4-5 14 2 4-7 45 2 15 7
50 q4-6h 1000 q12 400 q6h 250 q12h 25 q8h 100 q12h 25 q12h 150 q12h 25 q8h 30 q6h 20 q24h 250 q6h 50 q6h 1000 q24h
6000 4000 2400 1000 200 300 200 400 200 240 40 1000 400 2000
Proprionic acids
Ibuprofen Naproxen Ketoprofen Flurbiprofen
Acetic acids
Indomethacin Sulindac Diclofenac Ketorolac
Oxicams Fenamates
Piroxicam Mefenamic Acid Meclofenamate
Pyranocarboxylic acids
Etodolac
2.
Patients who are relatively non-tolerant and present with moderate to severe pain, or who fail to achieve adequate relief after a trial of a nonopioid analgesic, should be treated with a so-called "weak" opioid (Table
-136-
Cancer pain relief and palliative care
7.6); this drug is typically combined with a non-opioid and may be coadministered with an adjuvant analgesic.
-137-
Manual on the prevention and control of common cancers
Table 7.6. Opioid agonist drugs customarily used to treat moderate pain Formally called "weak opioids" (References 1, 4). Drug Dose (mg) equianalgesic to 10 mg morphine IM PO Duration Comments
Halflife (h) 2-3
of action (h) 2-4 Usually combined with a nonopiod. Available over the counter. Used for step 2 of analgesic ladder when in combination with a non-opioid. Usually combined with a nonopioid. Accumulation of its metabolite with renal impairment may cause seizures.
Codeine
130
200
Oxycodone
5
30
2-3
2-4
*Propoxyphene
100
50
2-3
2-4
* Not recommended for routine use.
3.
Patients who present with severe pain, or fail to achieve adequate relief following appropriate administration of drugs on the second step of the analgesic ladder should receive a so-called "strong" opioid (Table 7.7), which may also be combined with a non-opioid analgesic or an adjuvant drug.
Following the WHO Three-step analgesic ladder (Figure 7.2), the nonopioid analgesics are useful alone for mild to moderate pain and provide analgesia when combined with opioid drugs in the treatment of more severe pain. All non-opioid analgesics have a "ceiling" effect on analgesia and do not produce tolerance or physical dependence. It is reasonable to initiate therapy at a relatively low dose and then explore the dose-response relationship through gradual escalation until the ceiling dose is reached. The opioid compounds can be divided into agonist, agonist-antagonist, and antagonist classes. The pure agonist drugs are most commonly used in cancer-pain management. They do not appear to have a ceiling effect on analgesia. When the dose is increased, analgesic effects increase until either analgesia or sedation is achieved.
-138-
Cancer pain relief and palliative care
Table 7.7. Opioid agonist drugs customarily used to treat severe pain - Formally called "strong opioids" (References 1,4). Drug Dose (mg) equianalgesic to 10 mg morphine (SC) SC PO Duration Comments
Halflife (h) 2-3
of action (h) 3-4 MSG accumulation in renal failure predispose to toxicity.
Morphine
10
30 repeated dose
Oxycodone
5
15
2-3
2-4
Formulated as a single agent. Can be used for severe pain.
Hydromorphone
1.5
7.5
2-3
2-4
*Methadone
10
20
15190
4-8
Plasma accumulation may lead to late toxicity. Initiate dosing on prn basis. Not recommended for cancer pain. Contraindicated in patients with renal failure and those receiving MAO inhibitors. No oral formulation available. Less histamine release. Plasma accumulation may lead to late toxicity. Patches available to deliver 25, 50, 75 and l00 ug/h.
*Pethidine
75
300
2-3
2-4
Oxymorphone
1
10 (per rectum) 4
2-3
3-4
*Levorphanol
2
12-15
4-8
Fentanyl transdermal * Not recommended for routine use.
48-72
The mixed agonist-antagonist opioids and the partial agonist opioids have limited use because of a ceiling effect for analgesia, and a high prevalence of dose-dependent psychotomimetic side effects. A trial of opioid therapy should be administered to all patients with pain of moderate or greater severity. Patients with moderate pain are more commonly treated with a combination drug containing paracetamol or -139-
Manual on the prevention and control of common cancers
aspirin plus codeine. The dose of these combination drugs can be increased as a single agent, or the patient can be switched to a "strong" opioid. Those with severe pain, on the other hand, should be treated with an opioid customarily used in Step 3 of the analgesic ladder from the start.
Selection of analgesic agents The safe administration of non-opioid and opioid agents requires familiarity with their potential adverse effects. Non-opioids like aspirin and other NSAIDs have a broad spectrum of potential toxicity and caution is required in the administration of these agents to patients with blood clotting disorders, predilection to peptic ulceration, impaired renal function or concurrent corticosteroid therapy, and to older persons. Paracetamol has fewer side effects than the acidic non-opioid analgesics but hepatic toxicity may occur. Patients with chronic metabolic and liver disease can develop severe hepatotoxicity when the drug is not taken in usual therapeutic doses. In selecting an opioid, the younger patient without major organ failure can be started on any of the available agonist opioids. In this situation convenience of administration should be a major determinant, and morphine may be preferred. For older persons and those with major organ failure, short half-life drugs such as morphine are preferred because they are simpler to titrate and to monitor than long half-life drugs such as methadone. It is important to always review response to previous trials of opioid therapy. The report of side effects preventing adequate relief with a previously tried opioid may indicate the need for a trial of a different opioid drug to optimize the balance between analgesia and side-effects. Great caution is required in the use of propoxyphene, pethidine and morphine in patients with renal impairment.
Practical aspects of opioid administration Route Opioids should be administered by the least invasive and most convenient route capable of providing adequate analgesia for the patient. In routine practice, the oral route is usually the most appropriate.
-140-
Cancer pain relief and palliative care
Alternative routes should be used for patients with impaired swallowing and those with gastrointestinal obstruction. Rectal suppositories containing morphine are available, and controlledrelease morphine tablets can also be administered rectally. A transdermal formulation of fentanyl has also been developed. The sublingual route is effective for highly lipophilic drugs. Parenteral routes of administration in the form of repeated bolus injections, which may be administered by the intravenous (IV), intramuscular (IM) or subcutaneous (SC) routes, may be useful in some patients but are often complicated by the occurrence of prominent "bolus" effects. Repetitive IM injections have been a common practice, but they are painful, impractical, and their use is not recommended. Repeated bolus doses, if required, can be accomplished without frequent skin punctures through the use of an indwelling IV or SC infusion device. Dosing by SC routes proceeds in a manner identical to continuous IV infusion . Continuous infusions of drug combinations may be indicated when pain is accompanied by nausea, anxiety or agitation. An anti-emetic, neuroleptic or anxiolytic may be combined with an opioid provided it is non-irritant, miscible and stable in combined solution.
Schedule of administration Patients with continuous or frequent pain generally benefit from scheduled "around the clock" dosing. Pain that breaks through the regular analgesic schedule should be managed with a "rescue dose." Rescue drugs provide a method for safe and rational step by step dose escalation and are applicable to all routes of opioid administration. They may be given as supplemental doses, up to every one to two hours for oral rescue doses, or up to every 15 to 30 minutes for parenteral doses. The following dose should be titrated according to the amount of rescue doses required. Available controlled release preparations of morphine sulphate typically achieve peak levels three to five hours after administration and have a duration of effect of eight to twelve hours, thus lessening the inconvenience associated with "around the clock" drug administration. Regular morphine tablets or syrup are also available. Long-term patient-controlled anaesthesia (PCA), accomplished via the SC or IV route, is an ambulatory infusion device used to manage acute postoperative pain.
-141-
Manual on the prevention and control of common cancers
Dose selection and adjustment Patients in severe pain should generally begin with one of the opioids used for more severe pain at a dose equivalent to 5-10 mg oral morphine every three to four hours. When morphine is used, an IM:oral relative ratio of 1:3 is generally recommended. When patients are switched from one opioid drug to another, the equianalgesic dose table is used as a guide to the starting dose. Absolute dose is immaterial as long as the balance between analgesia and side-effects remains favourable. The development of inadequate pain relief should be addressed through a step by step escalation by a range of 30-50 per cent of the prior dose. Smaller dose increments do not significantly improve analgesia. Concern about tolerance should not impede the use of opioids early in the course of the disease. Since most patients who require an escalation in dose to manage increasing pain have demonstrable progression of the disease, analgesic tolerance is seldom the dominant factor in the need for opioid dose escalation. The worsening pain in a patient receiving a stable dose of opioids should generally be assessed as presumptive evidence of disease progression or, sometimes, increasing psychological distress.
Management of side effects A detailed understanding of adverse opioid effects, their prevention, and management will improve patient outcome. The most common adverse side-effects of opioids are constipation, nausea and vomiting. Other important dose-limiting adverse effects include sedation, delirium, myoclonus and respiratory depression. The likelihood of opioid-induced constipation is so great that laxative medications should be prescribed prophylactically to most patients. A combination of a softening agent (docusate) and a cathartic (senna, bisacodyl or phenopthalein) is frequently used as necessary. The incidence of opioid-induced nausea has been estimated to be 10-40 per cent and vomiting, 30-40 per cent. Tolerance to nausea and vomiting usually develops rapidly, and routine prophylactic administration of antiemetics is usually not indicated except in patients with a history of severe opioid-induced nausea and vomiting. Table 7.8 outlines the management of nausea and vomiting.
-142-
Cancer pain relief and palliative care
Table 7.8. Mechanisms of opioid-induced nausea and vomiting, and their management (Reference 1). Mechanism Suggestive clinical features Nausea and/or vomiting shortly after opioid administration. Anti -emetic drugs
Stimulation of the medullary chemoreceptor trigger zone
metoclopramide, prochlorperazine, chlorpromazine, haloperidol, corticosteroid, or lorazepam scopolamine, meclizine, or lorazepam metoclopramide
Enhanced vestibular sensitivity
Prominent movement-induced nausea and vomiting, or vertigo Early satiety, postprandial bloating or vomiting
Increased gastric antral tone
Sedation is often associated with the initiation of opioid therapy or significant dose escalation. In most cases, tolerance will develop to this effect after a few days to weeks. Some patients have a persistent problem particularly if other contributing factors exist, and will have to be actively treated (Table 7.9). Table 7.9. Step by step management of opioid-induced sedation (Reference 1). 1. 2. 3. 4. Eliminate non-essential central nervous system depressant medications. If analgesia is satisfactory, reduce opioid dose by 25 per cent. If analgesia is unsatisfactory, try addition of a psychostimulant. (starting dose: methylphenidate 5 mg bid, dextroamphetamine 5 mg bid or pemoline 18.75 mg bid) If somnolence persists, consider: - addition of a non-opioid or adjuvant that will allow reduction in opioid dose; - switch to a different opioid drug; - change to the intraspinal opioid (+) local anesthetic, or neurolytic techniques.
Opioid-induced cognitive impairment also appears to be transient in most patients. Although persistent cognitive impairment solely attributable to opioid use occurs, electrolyte disorders, neoplastic involvement of the CNS, sepsis, vital organ failure or hypoxemia usually contribute to its development. Again, a step by step approach to management is appropriate (Table 7.10).
-143-
Manual on the prevention and control of common cancers
Table 7.10. Management of Opioid-induced Cognitive Impairment (Reference 1). 1. 2. 3. 4. Eliminate non-essential centrally acting medications. If analgesia is satisfactory, reduce opioid dose by 25 per cent. Evaluate patient for concurrent causes (e.g. sepsis, metabolic derangement, intracerebral leptomeningeal metastases) and treat if possible. If delirium persists, consider: - trial of neuroleptic (Haloperidol); - switch to a different opioid drug; - change to the intraspinal opioid (+) local anaesthetic, or neurolytic techniques.
Myoclonus is a less common dose-related adverse effect of opioids which may resolve spontaneously. If the myoclonus is symptomatic and distressing, it can be treated empirically with a benzodiazepine, barbiturate or valproate. Switching to another opioid can be tried. Respiratory depression is the most serious adverse effect of opioid therapy but it is uncommon if the opioid dose is properly titrated. Clinically significant respiratory depression is always accompanied by sedation and mental clouding. Due to the risk of systemic withdrawal and return of pain, naloxone should only be administered for symptomatic respiratory depression. If the patient is arousable and the peak plasma levels of the opioid have been reached, the opioid dose should be witheld and the patient should be monitored until improved. If, on the other hand the patient is unarousable, naloxone should be used to improve ventilation using small bolus injections of dilute solution (0.1 mg in 10 cc saline) which is titrated against the respiratory rate.
Non-invasive intervention for patients unable to attain an acceptable balance between relief and side effects of systemic opioid therapy Even with optimal management of adverse effects, some patients do not attain an acceptable balance between pain relief and the side effects of an opioid. This can be resolved by non-invasive interventions such as (1) reduction of opioid requirement; (2) alternative pharmacological approaches (addition of non-opioid analgesic, addition of an adjuvant drug, switching to
-144-
Cancer pain relief and palliative care
another opioid); and (3) use of cognitive, behavioural or rehabilitative techniques. Adjuvant drugs are drugs that have a primary indication other than pain, but which have analgesic effects in some painful conditions. Corticosteroids are the most widely used general purpose adjuvant drugs. They ameliorate pain and produce beneficial effects on appetite, nausea, mood and malaise. Raised intracranial pressure, acute spinal cord compression, metastatic bone pain, neuropathic pain due to infiltration by tumour, and hepatic capsular distention, are some of the painful conditions that commonly respond to corticosteroid treatment. Neuropathic pain is due to nerve damage, and is described as burning, tingling, pricking or lancinating. Neuropathic pain may be nonresponsive to opioids but respond well to antidepressants and anticonvulsants. For continuous neuropathic pain low initial doses of antidepressants a re useful - amitripyline and imipramine (10-50 mg) may be given at bedtime and may be increased to a full therapeutic dose. For lancinating neuropathic pain, anticonvulsants are effective carbamazepine (20 mg twice daily) and valproic acid (500 mg at bedtime). Metastatic bone pains are optimally treated by combining opioids with an NSAID, or corticosteroids in difficult cases. Bisphosphonates, which inhibit osteoclastic activity, have also been shown to be effective in relieving malignant bone pain. Palliative radiotherapy should be strongly considered in addition to drug therapy for localized bone pain. Psychological interventions also play a role in the management of cancer pain. Cognitive behavioural interventions help reduce the perception of distress caused by the pain through the development of coping skills and by the modification of thoughts, feelings and behaviour. Relaxation techniques reduce muscular tension and emotional arousal or enhance pain tolerance. Other therapeutic modalities include transcutaneous electrical nerve stimulation (TENS), heat and cryotherapy. Immobilization devices enhance comfort for patients with pain precipitated by weight-bearing or ambulation.
Invasive interventions for patients unable to attain an acceptable balance between relief and side effects during systemic pharmacotherapy Patients who are unable to achieve a satisfactory balance between analgesia and side effects from systemic analgesic therapies may be
-145-
Manual on the prevention and control of common cancers
candidates for the use of invasive anaesthetic and neurosurgical techniques. These approaches, which include regional analgesic techniques (spinal and intraventricular opioids), neural blockade and neuroablative techniques, reduce the requirement for systemic opioids. Intraspinal opioid and local anaesthetic administration may achieve a satisfactory balance between analgesia and side effects without compromising neurological integrity. The use of neurodestructive procedures should therefore be based on an evaluation of the likelihood and duration of analgesic benefit, the immediate and long-term risks, the likely duration of survival and the anticipated length of hospitalization.
Use of sedation Sedation also plays a role in the management of intractable pain for patients who fail to benefit from other therapeutic methods. For some patients, adequate relief of physical symptoms can only be achieved at the cost of profound sedation. Sedation can be accomplished through the use of systemic opioids, with either benzodiazepine (e.g. lorazepam or midazolam), a neuroleptic (e.g. chlorpromazine or methotrimeprazine), or a barbiturate (e.g. thiopental) in combination with an opioid. The patient with advanced cancer and uncontrolled symptoms may choose transitory use of sedating therapy while continuing trials of analgesics. Controlled sedation can be offered initially as temporary respite therapy using a short half-life drug which can be titrated down to re-establish lucidity after an agreed interval or for preplanned family interactions. Alternately, patients with persisting distress despite an initial respite, and those in whom death is imminent may elect to be deeply sedated until death ensues. The ethical basis of the latter approach is based on the "principle of double effect," which distinguishes between the compelling primary therapeutic intent (to relieve suffering) and unavoidable untoward consequences (the potential for accelerating death). This approach recognizes the right of dying patients to adequate relief of pain, and the right of all patients to choose between appropriate therapeutic options. No patient should have to ask to be killed because of persistently unrelieved pain and no patient should be sedated without appropriate informed consent of the patient or proxy. It is the responsibility of the physician to ensure that the patient, family and attending staff have a comprehensive understanding of this intervention.
-146-
Cancer pain relief and palliative care
Successful long-term management requires continuity of care that provides an appropriate level of monitoring and responds quickly, flexibly and expertly to the changing needs of the patient. Patients with refractory pain, or unremitting suffering related to other losses or distressing symptoms, should have access to specialists in pain management, palliative medicine and psychooncology, who can provide expert assistance in the management of these complex problems. Treatment should always begin with a straightforward explanation to the patient of the causes of the pain. The patient should also be enlightened on the benefits and risks of each method of obtaining pain relief. When patients equally prioritize optimal comfort and function, the therapeutic goal is to achieve an adequate degree of relief without compromising cognitive and physical function. When comfort is the overriding goal of care, it may be appropriate to continue therapies that may impair cognitive function, or even foreshorten life expectancy.
Opioid Availability It is unfortunate that millions of people suffering from cancer pain are still not treated properly because of: 1) lack of concern by many governments, resulting in an absence of national policies on cancer pain relief and palliative care; 2) lack of professional awareness and education; 3) prevailing sociocultural perceptions that cancer is synonymous with suffering, and that nothing can be done about it; 4) overly restrictive regulations on the medical use of opioids, and an inadequate supply of drugs; and 5) fear of addiction. Traditionally, opioid analgesics have been used to manage acute pain. Long-term use of opioids has been discouraged because of the fear of tolerance or physical or psychological dependence. Research into the management of cancer pain has produced new knowledge about pain and how opioids act in the body in relation to pain. In general, studies on the use of opioids to treat pain in cancer patients indicate that the public and professional expectations about relief from cancer pain should be much higher than they are at present.
-147-
Manual on the prevention and control of common cancers
According to the Single Convention on Narcotic Drugs (SCND), the principal international treaty regulating the availability of opioids, the medical use of narcotic drugs continues to be indispensible for the relief of pain. It also, however, believes that addiction to narcotic drugs constitutes a serious evil. The convention classifies opioids; requires registration of all handlers and the estimation of medical needs for opioids; establishes rules concerning production, manufacture and distribution of opioids; and requires statistical reports on opioid consumption. It also governs how opioids are shipped between countries and defines to some extent the requirements for safe distribution within a country. The broad purpose of the convention is therefore to prevent the abuse of narcotics or opioids while guaranteeing their availability for medical use. The International Narcotics Control Board (INCB) is responsible for administering the SCND. A country obtains its supply of opioids for medical purposes by importation, domestic manufacture or both. These opioids are then distributed by manufacturers or wholesalers to hospitals and pharmacists, and subsequently dispensed to patients by health care personnel. Communication between health workers and drug regulators is essential in order to ensure that each understands the other's aims. It is important for health workers to understand the opioid distribution system in their own country, to learn about the national estimate of opioid needs and to be aware of the concerns of regulators. Morphine consumption varies greatly from country to country. Consumption figures do not completely indicate the extent to which opioids are used for treatment of moderate to severe cancer pain; they do, however, probably provide the best single indicator available. Opioid abuse is a reality and health care workers must cooperate in the campaign to prevent the diversion of opioids for non-medical use. Many countries have encountered difficulties in obtaining and distributing drugs for any type of illness. Inavailability of drugs may also be due to inadequate funding of health services, lack of health care delivery infrastructure and inadequate facilities for the storage and distribution of medicines. It is also important for the regulators to understand the importance of pain relief, both for individual patients and for public health in general. Information about cancer pain, where and how cancer patients are treated, and the training of health care personnel will help regulators whose job is to ensure the integrity of the distribution system. The knowledge that opioid use needs to increase will help regulators to make appropriate changes in the annual estimate.
-148-
Cancer pain relief and palliative care
Health workers should make the following salient facts about pain relief familiar to regulators: 1) Psychological dependence (drug addiction) is rare among cancer patients who receive opioids for pain relief. Confusion about physical dependence and psychological dependence or addiction has largely contributed, to the undertreatment of pain. Physical dependence is a pharmacological property of opiod drugs, defined by the development of withdrawal syndrome following either abrupt dose reduction or administration of an antagonist. Patients also become physically dependent on corticosteroids or beta antagonists, but are not considered addicted to these drugs. This problem is avoided by tapering of drug schedule if cessation is warranted, and if opioid antagonists are avoided. Addiction refers to the psychological and behavioural syndrome characterized by continued craving for an opioid drug to achieve a psychic effect and associated aberrant drug-related behaviour. Thus, the term addiction should never be used when physical dependence is meant. 2) Oral forms of morphine are preferred because the patient may be able to live at home and painful injections are eliminated. However, the oral dose needs to be two to three times higher than the injection dose to achieve the same degree of pain relief. Thus, the total amount of drug needed will increase significantly. 3) Pethidine, often relied upon for treatment of acute pain, is not recommended for patients with chronic pain because accumulation of a toxic metabolite may occur, causing myoclonus and seizure. Morphine and other opioids are preferred and should be included in the national estimate. Health care workers should tell regulators exactly which opioids are needed, including the dosages and dosage forms required, in order to ensure that the estimate is adequate to meet the needs of the patients. The use of opioids for patients may only be carried out by registered parties and only according to a physician's prescription. Certain records must be kept, and reports of consumption must be filed with the national regulatory authority. It is recommended that the hospice/palliative care governing body should adopt a formal policy that recognizes that pain and symptom management is a core purpose of hospice/palliative care, and that the availability of both opioid and non-opioid drugs must be ensured according to policies and procedures that are c onsistent with the WHO analgesic
-149-
Manual on the prevention and control of common cancers
method and legal requirements. The policy statement should assign specific responsibilities for implementation. The following questions should be addressed in formulating hospice/palliative care policy and procedures on opioid availability: 1. Responsibility for legal authorizations (A copy of the national narcotics control law and regulations should be available). •
What licences or registrations are necessary to fully comply with legal requirements? Who is responsible for obtaining licences and maintaining compliance? Who is responsible for maintaining communication with relevant government bodies?
•
•
2.
Responsibility for supply • •
What drugs and what dosage forms are necessary? If needed drugs are available at an affordable price in the country, who are the suppliers? If not, who is responsible for seeking assistance from the government drug control authority groups? Who is responsible for estimating the amounts needed? Who is responsible for ensuring that all steps to obtain opioids are accomplished in a timely way? Who is responsible for purchasing?
•
• •
•
3.
Responsibility for safety and monitoring • •
Who is responsible for receiving the supply? Who is responsible for maintaining safe storage according to legal requirements? Who is responsible for counting the drugs, calculating the balance, maintaining accurate records, monitoring consumption, and reporting and investigating any discrepancies?
•
-150-
Cancer pain relief and palliative care
4.
Responsibility for prescribing • •
Who is authorized to prescribe? Who is responsible for maintaining the supply of prescription forms? What are the restrictions on prescribing; for example, how much can go home? What records are required?
•
•
5.
Responsibility for dispensing •
Who is responsible for dispensing drugs, especially during evenings, weekends and holidays? What records are required?
•
6.
Responsibility for giving drug to patients •
Who is responsible for taking the drug from the supply to the patient? What records are required?
•
7.
Responsibility for emergencies •
Who is responsible for providing the drugs emergencies, increase in pain, vomited dose?
for
medical
•
Who is responsible for providing emergency supplies during evenings, weekends and holidays?
8.
Responsibility for disposal •
Who is responsible for returning or disposing of "left-over" medications? What records are required?
•
-151-
Manual on the prevention and control of common cancers
9.
Responsibility for informing patients and families about drug use • • • •
How and when to take. How to keep safe. Who to contact if there are problems. What should be done with left-overs.
10. Responsibility for updating policy according to needs and changes 11. Responsibility for educating current and new staff about policy
Relief of other symptoms Symptom management requires an understanding of underlying causes. Symptoms in advanced cancer are caused by the disease itself, either directly (e.g. intestinal obstruction due to cancer) or indirectly (e.g. decubitus ulcer due to debility); by the treatment given (e.g. adverse effects of anticancer drugs); or by a coexistent disorder (e.g. arthritis) that is unrelated to the cancer. A patient may have multiple symptoms. An unrelieved symptom (e.g. pain) may give rise to, or worsen other symptoms (e.g. dyspnoea, anxiety, anorexia), symptoms which in turn can accentuate the perception of the dominant symptom (e.g. pain) thus creating a vicious circle. Symptom management is often empirical (i.e. based on experience and observation) and evolves constantly in response to new research and clinical trials. There is already a large body of knowledge on how to successfully palliate the symptoms of patients with incurable cancer. Most of the methods can be implemented at home. Details on the management of individual symptoms can be found in the list of references and recommended readings.
-152-
Cancer pain relief and palliative care
General principles • Careful evaluation is the essential basis for symptom management and is the responsibility of both doctor and nurse. The evaluation should include not only physical problems but also social, psychological and spiritual aspects. This approach aims to build a picture of the disease itself, of the patient as a whole and the effects of the illness on the patient's quality of life. The priorities of evaluation are: • • • • to identify the patient's main symptoms and concerns; to listen carefully to what the patient is saying; and to believe what the patient is saying.
A detailed history should be taken, which should include questions about the main symptom(s). Supplementary information from the patient's relatives or care-givers is often invaluable.
Routine questions to evaluate the nature and severity of a symptom include: • • • • • • How does the symptom affect the patient's life? How does the symptom affect the patient's physical function and mobility? What makes the symptom better? Any particular position, activity, food or medicine? What makes the symptom worse? Is the symptom worse at any particular time of day or night?
The information obtained usually indicates one or more causes for the symptom(s) and provides a basis for effective treatment.
•
Teamwork. As in other areas of medical practice, palliative care requires coordination and cooperation among health workers, patient and family. Planning. Effective palliative care is based on planning and, as far as possible, anticipation of crises (e.g. regular examination of the mouth and skin identifies problems at an early, often asymptomatic stage). Some problems are easier to treat if detected early. Many problems
•
-153-
Manual on the prevention and control of common cancers
may be delayed, and even prevented, when they are anticipated and proper precautions are employed. Each patient needs an individual treatment plan which should be understood by all concerned: health workers, patient and family. • Preparation. Crises can often be prevented by careful planning. Health workers should make sure that the family is aware in advance of the problems that could occur, and of how to deal with them. Explanation. Patients, families and care-givers should be informed about the likely cause(s) of the symptom(s) and what treatment options are available. Such information should be given clearly and concisely, in words that are easy to understand. Education. Health workers are trained mainly within hospitals and therefore tend to learn a hospital model of care. Palliative care, however, is often based at home. Treatment plans should be adaptable for home use and must include education of patients and their families. Psychological distress tends to make symptoms worse. For example, severe dyspnoea almost always causes anxiety, which in turn may worsen dyspnoea. Treatment must address both physical and psychological aspects of symptoms.
•
•
•
Principles of Treatment Symptoms such as pain can often be relieved completely. Others, such as dyspnoea or intestinal obstruction, may be only partly relievable. When complete relief of symptoms is not possible, the aim of treatment is to help the patient move from a feeling of helplessness to a feeling of supremacy over the symptoms. Practical advise and psychological support are crucial to achieve this objective. Patients need help and support to maintain independence for as long as possible. Physical limitations may be reduced by treatment and mobility aids. Disease-specific treatment (e.g. radiotherapy for bone metastases to enable the patient to ambulate) may also be helpful, even if the illness is incurable. Such treatment should be given in combination with symptomatic treatment. A successful treatment plan requires accurate evaluation of the patient as described above and should consider non-drug methods and/or drug
-154-
Cancer pain relief and palliative care
therapy. The two approaches are often used in combination (multimodality treatment). Most symptoms can be improved by the following non-drug measures: • • explanation and reassurance; avoidance of factors that make the symptoms worse, and promotion of factors that make the symptoms better; correction of biochemical abnormalities (e.g. hypercalcaemia, hyponatraemia); treatment of concurrent disease (e.g. chest or urinary tract infections, cardiac failure); identification and treatment of psychosocial problems and disorders (e.g. anxiety, depression, delirium); and specific anticancer treatments (e.g. radiotherapy) which may be used to relieve symptoms, even in patients with incurable disease.
•
•
•
•
Drugs are the mainstay of management for many symptoms. Four principles underlie their use in palliative care: "By Mouth" Drugs should be given by mouth when possible. "By the clock" Drugs should be given at appropriate regular intervals to ensure continued relief of persistent symptoms. The timing of doses should take into account the pharmacology of the drug(s) and the metabolic state of the patient. "For the individual" Drug doses should be adjusted to achieve maximum benefit with minimum side effects. "Keep it simple" Treatment should be as straightforward as possible to ensure that the patient takes the right dose at the right time. Before a new drug is prescribed, the patient's other medications should be reviewed to exclude the possibility of drug interaction which may cause new symptoms to develop or worsen existing symptoms. The relevant drugs may have to be changed or discontinued.
-155-
Manual on the prevention and control of common cancers
Social, psychological and spiritual support Psychosocial aspects Unless the considerable social and psychological needs of patients with advanced cancer are recognized and attended to, relief of pain and other symptoms may be difficult to attain. These needs are common to cancer patients in all cultures. Many patients, however, will not raise psychosocial concerns without prompting. Health workers and carers must not only develop an awareness of these concerns, they must also be willing to spend the time that is required for their detection, evaluation and alleviation. The person closest to the patient may not be the next of kin, or even a relative. Health workers need to recognize and appreciate that the nature of close relationships varies widely. Lack of support for those caring for a patient at home is often the precipitating factor in the admission of a dying patient to hospital. The social worker should be an integral member of the palliative care team, providing additional psychological support for both patient and family and helping to identify and resolve practical, social and financial problems. Good support should include the following elements: • Practical support. This should include, when indicated, instruction in skin care and the prevention of bedsores, how to lift a paralysed patient and how to cope with incontinence. Support of this kind can be provided by general medical practitioners, community nurses, physiotherapists, occupational therapists, social workers or welfare officers. Emotional support. Family carers should be the patient's main source of psychological support and they can be helped in this role by appropriate counselling. They should be made aware of the patient's psychological needs and of common reactions to life-threatening illness. Nurses, social workers and physicians will usually be responsible for this aspect of family support, b ut trained volunteers and community groups can effectively supplement family and professional support.
•
-156-
Cancer pain relief and palliative care
•
Day care and inpatient beds for respite care. In some cases, a patient's attendance at a day care centre and/or admission to a palliative care centre or hospital as an inpatient may be necessary to provide respite for family carers. Farewell leave. In developing countries, most patients die at home in the care of the family. In developed countries, by contrast, death more often occurs in an institution, although much of the terminal care could be provided as effectively and more economically by the family. Countries with a health care structure that allows, for example paid maternity leave, should consider establishing paid leave for those who care for the terminally ill. Denmark has already introduced this concept: when a physician has judged that further anticancer treatment is futile, paid leave is granted to a close relative to care for the patient at home when possible and desirable. In 1989, Sweden introduced 30 days' paid leave for the principal carer. In Norway, although no official mechanism for paid leave has yet been established, a similar system frequently operates: the physician declares that a close relative or friend is the key carer and then arranges for standard sick-leave compensation. Bereavement support. There is evidence that those who lack support in their bereavement have a higher rate of morbidity. All relatives and friends will need to discuss the events surrounding the death of the patient. This can be encouraged by attentive listening by a professional health care worker or suitably trained volunteer. They may need to be followed up for several months, sometimes much longer, and this is particularly true for bereaved people with limited social support. To be effective, a bereavement programme must have defined goals and a consistent method of follow-up, and must concentrate its efforts on those individuals at greatest risk.
•
•
If the psychosocial care of cancer patients is to be satisfactory, professional health care workers must be trained in psychological assessment and counselling skills. Few physicians and nurses involved in cancer care receive any formal training in these areas and often have little time available in the working day for their application.
-157-
Manual on the prevention and control of common cancers
Basic skills that should be taught to and mastered by all physicians, nurses and social workers include: • recognition of the nature and prevalence of the psychosocial distress associated with cancer and its treatment; knowledge of the signs and symptoms that distinguish morbid reactions, requiring special intervention, from normal reactions; ability to acknowledge, clarify and organize key verbal and nonverbal cues that patients and relatives give about their problems; ability to maintain the focus of an interview, helping patients and relatives stick to the point without alienating them; ability to explore highly emotive topics, e.g. worry about the future or the impact of illness on a personal relationship, in a way that is constructive yet allows the expression of feeling; and the use of open-ended ("How are you feeling?") and non-directive questions ("How did you feel about having a stoma?").
•
•
•
•
•
These skills can be improved through the provision of written and visual materials that make the methods more explicit. In addition, practice through role-play with videotape feedback of performance will enhance learning. Situations that are most commonly practised in role-play include: • • • basic psychological assessment; breaking bad news; coping with a patient who has been misled about his or her prognosis; handling difficult questions; dealing with anger; challenging denial: establishing dialogue with a withdrawn patient; and facing relatives after the death of the patient.
• • • • •
-158-
Cancer pain relief and palliative care
Published data indicate that the acquired skills persist, but follow-up workshops within 6-12 months of the original teaching sessions would help consolidate learning and facilitate the discussion of difficulties encountered in clinical practice. Participants could then move on to more advanced counselling tasks. Training within the working environment is an alternative approach. Ideally, it should be possible to offer training to staff at all major cancer centres with the help of suitably trained and experienced tutors. More teachers will be needed if training in assessment and counselling is to be improved. Cancer specialists, psychiatrists, psychologists, specialist nurses and social workers already committed to improving psychological and social care are clearly valuable resources. Most of them, however, need training in the use of appropriate teaching methods.
Spiritual aspects "Spiritual" refers to those aspects of human life relating to experiences that transcend sensory phenomena. This is not the same as "religious", though for many people the spiritual dimension of their lives includes a religious component. The spiritual aspect of human life may be viewed as an integrating component, holding together the physical, psychological and social components. It is often perceived as being concerned with meaning and purpose and, for those nearing the end of life, this is commonly associated with a need for forgiveness, reconciliation and affirmation of worth. Patients should be asked about the spiritual aspects of their lives. Some find these areas vague, or even threatening, and questions must be asked gently, with full respect for the patients' rights to their own values and beliefs, and acceptance of their right to remain silent about them. Information about patients' concepts of deity may be elicited by asking whether religion or God is significant to them and, if so, by asking for a simple description. Questions that focus on sources of hope and strength may also open up this area of care, (e.g. "To whom do you turn when you need help?"). It is important to enquire about religious practices, with special attention to those that impinge upon hospital life or health care. Questions that focus on the relation between spiritual beliefs and health may also be
-159-
Manual on the prevention and control of common cancers
helpful (e.g. "Has being sick made any difference to your beliefs or to the practice of your religion?") Patients have the right to expect that their spiritual experiences will be respected and listened to with attention. The relating of such experiences, and the reflection on their meaning, frequently offer a kind of inner healing. When patient and carer have a relationship based on mutual respect and trust, there can be a place for the sharing of stories, conversations about the meaning of life and the purpose of suffering, and even participation in religious rituals. A caring relationship that is able to incorporate spiritual aspects has added potential for inner healing. Two premises must be borne in mind: • Respect for people's beliefs is imperative. Carers do not have to agree with people's beliefs or practices in order to take them seriously. Non-believers can affirm their contribution to a sense of well-being and integrity in others. Supportive intervention in this area must be offered in ways that are non-sectarian, non-dogmatic and in keeping with the patient’s own views of the world. Patients who wish to participate in private or communal spiritual or religious activities must be enabled to do so. At times they may need privacy and access to spiritual advisers.
•
Cancer pain relief and palliative care in children Cancer in children is a major health problem. Each year approximately one hundred and thirty million children between 0-14 years of age develop cancer. In developed countries it is the single leading cause of death from disease in 1 -14 year olds. Approximately 67 per cent of children can be cured when they are diagnosed early and receive curative therapies. The specific cure rate depends upon the type of cancer. Unfortunately, however, most children with cancer do not receive curative therapies because the majority are in developing countries. Because their disease is too far advanced by the time they are diagnosed, because curative therapies are not available and because the treatment of childhood cancer has not been a priority in all countries, most children with cancer in developing countries will die. Thus, the emphasis of care for many children should be primarily palliation.
-160-
Cancer pain relief and palliative care
Almost all children with cancer experience some pain during the course of their illness: pain caused by disease; by invasive procedures; by treatments; and by psychological distress. At present, there are no accurate figures on the worldwide magnitude of different types of cancer pain in children, because countries differ widely in their diagnostic capabilities and reporting systems. However, recent documentation of childhood cancer pain within specific treatment centres in developed countries indicates that all children with cancer do experience pain related to their disease and/or treatment, with more than 70 per cent of children suffering from severe pain at some point. Unfortunately, children's pain is often not recognized and, if recognized, is o ften inadequately treated even when resources are available, and even though pain relief is an achievable goal. Unrelieved pain places an enormous additional burden on children and families. Children become afraid of future pain and mistrust and fear hospitals, staff, needles and other procedures. With pain, children become irritable, anxious and restless. They may develop night terrors, flashbacks, sleep disturbance and eating problems. Children with uncontrolled pain may feel victimized, depressed, isolated and lonely. Pain may also impair the child's capacity to cope with cancer treatment. Families of children who are in pain often feel anger and distrust of the medical system, and depression and guilt for not being able to prevent their child's pain. They may have conflicts with their child and will have disturbing memories of their child's pain and suffering. Poorly-managed pain also affects health care workers. It numbs empathy, creates guilt and encourages denial that children are suffering. The effects of poorlymanaged pain endure for the child and family. Children can suffer from post-traumatic stress symptoms, phobic reactions, depression and increased pain years after the end of treatment. Several misunderstandings have fostered inadequate pain control in children with cancer. These include: • unfounded fears of drug addiction, so that opioid analgesics are administered only as a last resort and children often do not receive the potent analgesics required to relieve severe cancer pain; misunderstanding of the pharmacodynamics and pharmacokinetics of opioid analgesics in children, so that drugs are prescribed at inadequate doses, inappropriate dosing intervals, and through painful or less effective routes of administration; lack of knowledge about the nature of a child's perception, so that many individuals who treat children with cancer fail to evaluate and treat a child's pain based on all causative and contributing factors; and -161-
•
•
Manual on the prevention and control of common cancers
•
lack of information about the simple physical, behavioural, cognitive and supportive methods that reduce pain, so that health professionals do not teach practical methods that effectively reduce cancer pain and suffering to children and parents.
The nature of children's pain From a very young age, children understand the basic concept of pain and can describe both its emotional and physical aspects. Yet, pain is a difficult sensation to define simply and precisely. The International Association for the Study of Pain (IASP) define "pain" as: "An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage." Pain is always subjective. Each individual learns the application of the word through experiences related to injury in early life. It is unquestionably a sensation in a part or parts of the body, but it is also always unpleasant and therefore also an emotional experience. Health providers must recognize that each child, parent and sibling reacts to a potentially fatal illness individually, in a manner consistent with his/her own personality and past experience and the particular meaning of the disease. To support and assist children, one must know the children and their families, their beliefs about life and death and their current sources of emotional support. Such an approach represents the concept of palliative care.
Types of cancer pain in children Almost all children with cancer experience pain at some point during their illness: pain caused by the cancer itself, by treatments, by invasive diagnostic or therapeutic procedures, and incidental pain from unrelated causes. Childhood malignancies differ from adult malignancies in that children suffer more commonly from haematologic neoplasms than solid tumours. When curative therapies are available, children's cancer often responds promptly to treatment and they experience prompt pain relief. However, some children may suffer persistent pain for a lengthy period. When curative therapies are not available, death is often rapid.
-162-
Cancer pain relief and palliative care
The most common childhood malignancies, such as leukaemia, lymphoma and neuroblastoma, often produce diffuse bone and joint pain. Leukaemia and lymphomatous disease, along with brain tumours and certain solid tumours, can produce headaches from meningeal irritation and obstruction with increased intracranial pressure. Disease-related pain can be secondary to that caused by procedures or to treatment side effects. For many children, these pains are the worst part of their disease, account for the majority of the pains they experience, and intensify as repeated procedures are required. Procedures include (1) diagnostic and therapeutic procedures, such as bone marrow aspirations, lumbar punctures or venipunctures and (2) surgical procedures for diagnostic or therapeutic purposes such as amputations. Children can experience many types of pain caused by the side effects of chemotherapy, radiation and medications. These include: mucositis, neuropathies, radiation reactions, and infections from neutropenia. In the developed world, the major sources of pain in children's cancer are diagnostic and therapeutic procedures. In the developing world, the major source of pain is disease-related pain.
Therapeutic strategies Comprehensive pain management includes active treatment of the cancer as well as pharmacological and non-pharmacological interventions to decrease pain and suffering. These methods can be incorporated into a flexible programme for children in which parents, siblings and significant family and community members assist the health care team. The management of a child's cancer pain begins with a comprehensive physical examination and pain assessment to determine the sensory characteristics of the pain (location, quality, intensity, duration), the primary underlying etiology and the secondary contributing physical and psychological factors. For effective pain relief, treatment must be targeted to the primary pain source and to the multiple secondary sources. The chronology of the disease, previous therapy and the child's individual characteristics must be considered carefully, in order to select the most appropriate drug and non-drug therapies. Children's cancer pain can be controlled if basic principles of pain management are followed. While complete relief of pain may not always be possible, this strategy will significantly improve pain control for all children.
-163-
Manual on the prevention and control of common cancers
Pain assessment Pain assessment facilitates diagnosis and disease monitoring, and enables the health professional to alleviate needless suffering. Information about pain - location, quality, severity and duration - should be viewed as important clinical signs. A child's pain may signal a change in the disease process. Pain assessment is a continuous process because the disease process and the factors that influence a child's pain change over time. Thus, pain assessment must include not only measuring pain severity at a given point in time, but must also include an evaluation of how each of the health care, child and family factors may influence the pain. The responsibility for pain assessment should be shared by the child's relevant carers, both health professionals and the concerned people surrounding the child. The ABC of pain assessment in children:
Always
evaluate a child with cancer for potential pain, because children may experience pain even though they may not tell you in words. Infants and toddlers can only show their pain by how they look and act. Older children may deny their pain for fear of more painful treatments.
Be
careful to consider pain as an integral part of the physical examination. Physical examination should include checking their muscles, bones, spinal areas and viscera for potential pain sites. The child's reactions during the examination - grimacing, contracture, rigidity, etc. - may indicate pain.
Consider the impact of family, health care and environmental factors on the child's pain.
Document
the child's pain severity on a regular basis. Use a pain scale that is simple and appropriate for the developmental level of the child, and applicable within the cultural context in which it is used.
Evaluate the effectiveness of pain interventions regularly and modify the treatment plan as necessary, until the child does not have pain. There are many ways to document a child's pain severity to obtain an accurate and ongoing record. It is possible to make some degree of assessment of any child's pain, even the critically ill or cognitively impaired child. When children are unable to describe their pain in words
-164-
Cancer pain relief and palliative care
they must be carefully watched for behavioural signs of pain. Pain behaviour may vary depending on whether or not the pain is brief or persistent. Many young children exhibit more obvious physical distress when a brief pain is strong. In contrast, children with persistent pain usually exhibit more subtle signs of pain. Thus, parents and significant family members have a particularly important role in their pain assessment because they know their children and recognize the very subtle changes in a child's manner or behaviour that are caused by pain. Younger children (under 6 years of age) will only be able to describe the general amount of pain they feel, while older children can also describe other aspects -- the severity, quality, location, duration, and changes in the pattern over time. Assessing pain severity as "there", or "not there," or on three levels, such as "small," "medium", and "large" can be adequate for a child. All pain scales are based on the concept of counting, which is universal. Thus, practical pain tools can be developed for all cultures. When possible, you should ask a child "how strong is your pain now?" Children could answer comparing their pain severity, for example, to the number of fingers they show (0-10), to the distance between their hands (close - far apart), or to units of the country's currency (e.g., number of rupees), or they could use tools, such as an abacus or ruler. The same pain scale should be used to assess the child's pain as their response to intervention. Appropriate pain control therapies should be adjusted until the child's pain is controlled. A child's pain level is an essential vital sign and should be regularly recorded on the child's medical record.
-165-
Manual on the prevention and control of common cancers
Guidelines for non-drug pain therapy Non-drug therapies must be an integral part of the management of children's cancer pain, beginning at diagnosis and continuing throughout treatment. These therapies can easily be used in different settings and may modify many of the factors that usually increase children's pain. In some situations they activate sensory systems that block pain signals. At other times, they trigger children's own internal pain-inhibitory systems. Non-drug approaches supplement drug methods. They are not substitutes for appropriate drug treatment. Non-drug pain therapies may be categorized as supportive, cognitive, behavioural or physical. Supportive therapies support and empower the child and the family. Cognitive therapies influence children's thoughts. Behavioural therapies change behaviour and physical therapies change children's sensory systems.
Supportive methods Supportive methods are basically good psychosocial care of children. The first principle is that care is family-centred, in other words, based on the family's and the child's needs. An important aspect is parental involvement in decision-making and in providing comfort to children. Parents need a receptive environment and they may need instruction in how best to help their child. The importance of the family in ensuring the general health and well being of children was recognized in a World Declaration on the Survival, Protection and Development of Children at the World Summit for Children. Another element of family-centred care is making the clinic or hospital environment friendly to families. This will include having liberal visiting hours and a physical atmosphere conducive to family participation. Even more important is making a child's family and community feel welcome. Throughout the world, culturally-specific pain-reduction techniques or folk remedies, are used. They reflect the traditional wisdom, loyalties, and trust of the family, and the social sanctions of the community. It is important to respect folk remedies and to establish their compatibility with treatment, taking care not to alienate the family.
-166-
Cancer pain relief and palliative care
If families are not accurately informed about the diagnosis and treatment plan, they cannot participate. Information is accepted best if it is tailored to the needs of the child and the family. Health care providers should individualize their approach, depending on the family's style. Information is best given empathically, in small doses and repeated frequently as needed. Booklets, videos, drawings and dolls can be used. Lying to children about painful procedures will cause them to distrust what will be done to them in the future. Some families will want greater involvement than others. In some settings the community will be able to provide support. It is best to give the child choices about w hich techniques to use to control pain. Choice is also desirable for decisions which do not interfere with treatment such as which finger to stick. Play is an essential part of every child's daily life and even the most seriously ill child can be supported to play. Therefore, all children must have the time and place to play, and painful procedures must not be done in play areas. Normal activities such as school, visits by friends, hobbies and work should be encouraged.
Cognitive methods Cognitive methods involve influencing the child's thoughts and images. Parents are often very skilled at using cognitive methods because they know their child's preferences. Distraction actively absorbs children's attention. The more involved the child is in the activity the more likely it is to distract from pain. Infants and young children require concrete events or objects to attract their attention. Interesting toys with things to see, hear and do are usually best. Older children benefit from concentrating on a game, conversation or a special story. Music, which can range from a mother's lullaby to a music recording on a tape recorder, is a universal soother and distractor. It is best to have the child select the music. Imagery is the process in which a child concentrates on the image of a pleasant and interesting experience instead of the pain. Children can be helped by an adult to become absorbed in a previous positive experience or an imaginary experience or adventure. Storytelling is a powerful way to engage children's imagination and to distract them.
-167-
Manual on the prevention and control of common cancers
Behavioural methods Deep breathing is a simple way to help the child to reduce pain and gain self-control. Deep breathing focuses the child's attention, reduces muscular tension, relaxes the diaphragm and oxygenates the body. It is best to start teaching this by asking the child to breathe out, and let go the tension, or scary feelings, with each breath. Younger children can be taught to breathe deeply by blowing bubbles made from liquid soap or by using party blowers. Older children can use more sophisticated breathing techniques such as breathing in and out, each for the count of three. Progressive relaxation is a useful technique for adolescents. Sequential tensing and relaxing of muscle groups is done while the teenager is lying down. Relaxation is often combined with suggestion and deep breathing. These methods can reduce anticipatory anxiety and help reduce nausea and vomiting.
Physical methods Touch is important for all children, particularly the pre-verbal child, who understands the world through touching and feeling. Touch must be appropriate for the children's needs, that is, not too invasive either physically or psychologically. Touching includes: stroking, holding and rocking, caressing, massaging hands, back, feet, head, tummy and swaddling. Vibration or tapping can also be comforting. When talking takes too much effort, touch can be the best form of communication. Cuddling is a form of touch that combines several different aspects and is a comfort to most children. When touching the child for medical purposes, e.g., palpating an abdomen, care must be taken to use warm hands, to proceed gently, talking quietly with the child about what is being done. Heat and cold are often easily available. Ice wrapped in a cloth can be used for disease pain, inflammation, or for procedure pain such as intramuscular injection. Ethyl chloride spray offers some anaesthesia for the pain from needle punctures. Heat is useful for muscle pain. Cold and heat should not be used on infants. TENS or Transcutaneous Electrical Nerve Stimulation consists of a battery operated device that delivers electrical stimulation trough electrodes placed on the skin. Children often experience TENS as tingling or tickling. It must not be painful. TENS is simple to use, effective and requires little preparation. Children and their families can often use TENS
-168-
Cancer pain relief and palliative care
after simple instruction and an explanation as to what the unit looks like and what the child may feel.
Guidelines for analgesic drug therapy When analgesic drugs are used correctly, pain can be relieved in most children. The four concepts underlying the use of analgesics for relieving children's cancer pain are "by the ladder", "by the clock", "by the appropriate route," and "by the child".
"By the Ladder" The same principles of the WHO Three-Step Analgesic ladder described earlier for adult patients are also used for children.
"By the Clock" Medications should be administered on a regular schedule by the clock, not on a pro re nata (prn) basis -- unless a child's pain episodes are truly intermittent and unpredictable. On a prn basis, children must experience pain before they are able to obtain pain relief. They may fear that their pain cannot be controlled and may become increasingly frightened. In addition, the doses of opioids required to relieve existing or breakthrough pain are higher than those required to prevent the recurrence of pain.
"By the Appropriate Route" Medications should be administered to children by the simplest, most effective and least painful administration route; this is usually by mouth. Analgesics may be administered optimally by the oral route in tablets and elixirs. Alternatively, the intravenous, subcutaneous and transdermal routes can be used. In general, intramuscular injections should not be used unless absolutely necessary as they are painful and frightening to children who, as a result, may not request pain medication or may deny that they have pain when checked by the medical staff. Rectal administration is unpleasant for many children but is preferable to intramuscular administration. If injections are necessary, a mixture of
-169-
Manual on the prevention and control of common cancers
2.5 per cent lidocaine and 2.5 per cent prilocaine, in the form of a cream, or other topical formulations of lidocaine, helps in reducing pain caused by needles. A new approach is patient-controlled analgesia (PCA), a method for administering drugs either intravenously or subcutaneously, in which children, over about seven years of age, push a button to give themselves a rescue dose of drug for breakthrough pain. A pre-set analgesic dose is delivered into an infusion line by a computer-driven pump. For safety, there is a timed lock-out period after each dose so that additional doses cannot be delivered for a specified time period. PCA may be used alone or with concurrent continuous infusions.
"By the Child" Doses of all medications must be based on each child's circumstances. There is no one definite dose that will be appropriate for all children with pain. The goal is to select a dose that prevents children from experiencing pain before they receive the next dose. It is essential to assess and record the child's pain regularly and adjust analgesic doses as necessary to control pain. The effective opioid dose to relieve pain varies widely among different children or in the same child at different times. Doses must be based on the individual child's pain level. Some children require very large massive opioid doses at frequent intervals to control their pain. If such large doses are necessary for effective pain control and the side-effects are minimal or can be managed by adjunctive medications so that children are comfortable, then the doses are appropriate.
Specific drugs for pain relief Non-opioid analgesic drugs These drugs are used to relieve mild pain, or in combination with opioids, to relieve moderate pain. All have analgesic and antipyretic effects and, except for paracetamol, anti-inflammatory effects. Paracetamol is the drug of choice because it has a very high therapeutic ratio for children. The recommended dose is 10-15 mg/kg orally every four to six hours. Unlike acetylsalicylic acid, paracetamol does not have gastro-intestinal and haematological side effects or the possible association with Reye's syndrome. Newborn and young infants tolerate paracetamol without -170-
Cancer pain relief and palliative care
difficulty. The use of acetylsalicylic acid and other nonsteroidal anti-inflammatory agents (NSAIDs) is more restricted in children than adults with cancer: the potential for bleeding problems is a major concern, as children with cancer often have very low platelet counts. NSAIDs are useful for children with bone metastases who have adequate platelet counts. They should be used with caution in newborn infants. Ibuprofen (10 mg/kg orally every six to eight hours) and indomethacin (1-3 mg/kg orally every six to eight hours - not indicated in children of less than 12 years) are the examples in the WHO Model List of Essential Drugs. Increasing the dose of non-opioids beyond the recommended therapeutic level produces an analgesic "ceiling effect" in that there is little additional analgesia, but a greater increase in side-effects and toxic reactions. If a non-opioid, with or without an adjuvant drug, fails to adequately relieve mild to moderate pain, an opioid for mild to moderate pain should be added. If the pain is severe, an opioid for moderate to severe pain should be added.
Opioid analgesic drugs for mild to moderate pain Codeine is the drug of choice for children in this category. The recommended starting dose is 0.5-l.0 mg/kg orally every four to six hours for children over six months of age. As with strong opioids, the dose of codeine for children less than six months should be one-quarter to one-third the comparable milligram per kilogram dose for older children. Codeine is usually administered in fixed combinations with non-opioids (usually paracetamol). Parenteral preparations of codeine, if used, should be administered at two-thirds of the oral dose. If a child continues to have pain at this dose, codeine should be discontinued and a strong opioid administered because doses above this level may increase the side effects without greatly improving analgesia.
Opioid analgesic drugs for moderate to severe pain Strong opioid analgesics are required to relieve severe pain in children with cancer. These drugs are simple to administer and provide effective pain relief in the majority of children. Opioids can be used alone or combined with non-opioids or adjuvant analgesic drugs, depending on the sources of a child's pain. Pain relief can be enhanced by continuing the NSAID or paracetamol with the addition of an opioid. Strong opioids have no fixed upper dosage limit. Thus, there is no maximum dose for strong opioids because there is no analgesic ceiling effect. The right dose is the dose that is adequate to relieve the child's pain. Children may require extremely large doses to obtain pain relief, -171-
Manual on the prevention and control of common cancers
sometimes as high as a thousand-fold escalation of the standard starting dose. Anyone treated with opioids for more than seven days will develop physiological dependence. In these children, opioids should not be discontinued without gradual tapering to avoid symptoms of withdrawal. A typical tapering regimen might be a 50 per cent reduction of the dose for two days, followed by a 25 per cent dose reduction every two days until the child is taking an opioid dose which is equianalgesic to an oral morphine dose of 0.6 mg/kg/day if the child is under 50 kilograms or 30 mg/day if over 50 kilograms. At that time, the drug can be discontinued. Other side effects such as constipation, nausea, itching and sedation are common when using opioids and they should be anticipated and treated aggressively. Parents should be advised that there may be some sedation with initial dosing, which generally abates within a few days. If not prepared for this, they often worry unnecessarily that this somnolence is indicative of disease progression and infer that their child may be dying. The pharmacokinetics of morphine in young infants differ from those in older infants and children and, as a result, initial opioid dosing on a milligram per kilogram basis in infants less than six months of age should be one-quarter to one-third the comparable dose for older children. For infants, opioids should be administered in a setting where continuous observation and immediate intervention are possible, because opioids can cause delayed respiratory depression. Initial opioid dosing should also be reduced in patients with severe malnutrition, hepatic and renal dysfunction, multi-organ system failure or pre-existing sedation. Non-opioid analgesics have a ceiling effect. Opioid drugs do not. The correct amount of opioid is the dose that relieves the pain to a tolerable level with an acceptable degree of side effect. The strong opioid of choice included in WHO's Model List of Essential Drugs is morphine. Alternatives are hydromorphone, methadone and fentanyl. Pethidine has no major advantage. Moreover, since a toxic metabolite, norpethidine, accumulates during therapy causing central nervous system excitation, myoclonus and seizures, it is not recommended for children with pain.
Morphine Morphine is the drug of choice for controlling severe pain for most children. The recommended starting dose is 0.3 mg/kg orally every four hours, titrated individually until the child has pain relief. Oral -172-
Cancer pain relief and palliative care
preparations of morphine sulfate and morphine hydrochloride are available. The aqueous solutions are bitter, so children prefer the drug mixed in a flavoured syrup. The morphine solution should be stored in a dark bottle, out of direct sunlight and in a cool place. An antimicrobial preservative is necessary, particularly in warmer climates. If the oral route is not possible, continuous intravenous or subcutaneous infusions at 0.03-0.05 mg/kg/hr are effective methods for producing a constant analgesic effect. Alternatively, intermittent doses starting at 0.1 mg/kg can be given every two to three hours through an indwelling SC or IV line. During long-term administration, oral dosing of morphine requires two to three times the comparable parenteral milligram per kilogram dose. If prolonged pain is anticipated, controlled-release oral morphine preparations are available. They may be given at eight-twelve hour intervals, so fewer daily doses are required and children can sleep without interruption. Tablets vary in strength from 10 to 200 mg, but are not available in all countries. Crushing tablets eliminates the controlled release properties. The recommended starting dose is 0.6 mg/kg every eight hours or 0.9 mg/kg every 12 hours. This preparation is more difficult to titrate to effect than regular morphine. Thus, to titrate the correct dosage, first administer regular oral morphine every four hours with appropriate upward titration to achieve pain control throughout a 24-hour period. Then, convert to the controlled-release preparation by administering half of the total 24-hour oral morphine dose that provided effective p ain relief every 12 hours, or sometimes, a third of the total 24-hour dose every eight hours.
Adjuvant drugs The role of adjuvant drugs is similar to that described earlier for adults. These adjuvant drugs should not be prescribed routinely. Instead, their role in cancer pain management should be based on the needs of each child. Continual reassessment of the indications for and the efficacy of the adjuvant drugs guides their use for children with acute or chronic pain.
-173-
Manual on the prevention and control of common cancers
Sedatives, hypnotics and anxiolytics The benzodiazepines have a number of important indications for children with cancer. Diazepam and lorazepam are recommended for the short-term alleviation of acute anxiety and muscle spasms while midazolam is often used to pre-medicate children for painful procedures. Benzodiazepines cause sedation and can enhance opioid-induced sedation. The recommended dose of diazepam as an anxiolytic and muscle relaxant is 0.05-0.1 mg/kg PO to a maximum initial dose of 5 mg/dose every four to six hours, with gradual escalation as required. Lorazepam is dosed at 0.02-0.04 mg/kg IV or PO with a maximum initial dose of 4 mg/dose every four to six hours, given as needed. Side effects include sedation, depression, and dependence with prolonged use. Diazepam should be used with caution in neonates. The dose of midazolam is 0.05 mg/kg intravenously five to ten minutes prior to the procedures, and can be repeated twice. Although midazolam is available only as a parenteral solution in some countries, it can be administered orally by mixing the parenteral solution with flavoured syrup. The oral dose is 0.3-0.5 mg/kg with a maximum initial dose of 5/mg/dose 30-60 minutes prior to the procedure.
Corticosteroids Corticosteroids are useful in relieving pain from inflammation associated with nerve compression, headache from raised intracranial pressure, and bone metastases. Prednisone, prednisolone, and dexamethasone are the most commonly used drugs; dosage depends on the clinical situation. The projected time course for continued steroid use should be carefully considered when planning use of a steroid as an adjuvant. Side effects include oedema, dyspeptic symptoms, and occasionally gastrointestinal bleeding. Gastrointestinal side-effects may be increased if corticosteroids are used in conjunction with nonsteroidal anti-inflammatory drugs. Hypertension, proximal myopathy, agitation, hyperglycemia, psychosis and opportunistic infections may result. The mood changes and weight gain can be profoundly distressing to children and teenagers. After prolonged use, adrenal suppression may occur and requires a gradual tapering of corticosteroids prior to discontinuation.
Anaesthetic and neurosurgical procedures There is a limited role for anaesthetic and neurosurgical procedures in pain management in children with cancer. Epidural and intrathecal administration of opioids and local anaesthetics may be used to manage pain in children who do not receive adequate pain control from oral and -174-
Cancer pain relief and palliative care
parenteral opioids combined with adjuvants and delivered in adequate doses, or who suffer unacceptable side-effects. Spinal routes eliminate the need for repeated needle punctures. These specialized techniques should be performed by experienced paediatric anaesthesiologists. Deep sedation or general anaesthesia may be used to relieve pain during invasive procedures.
Procedure-related pain For children receiving curative therapies, the pain of required diagnostic and therapeutic procedures is often worse than the cancer itself. Aggressive approaches to the management of procedure pain are particularly necessary in children with cancer because these children may require multiple procedures in the future. Procedures performed with inadequate pain control can create a state of anxiety in the child which can significantly increase pain during subsequent procedures, alter relationships with health care providers and decrease compliance with medical advice. Procedure-related pain should be treated prophylactically using both pharmacological and non-pharmacological approaches. The specific approaches used should be tailored to the individual child, depending on the specific procedure and the child's and family's needs and preferences. Children must be adequately prepared for all invasive and diagnostic procedures - finger pricks, bone marrow aspirations, and imaging scans. They should know what will happen, how it will be done, and they should be prepared for any unusual sights, smells and sounds. If possible and culturally appropriate, parents should be present and involved in the procedures to provide comfort to their child. They should not be asked to restrain their child for the procedure. Procedures should take place in a specially designated treatment room and not in the child's room which should, if at all possible, remain a refuge from painful events. The competency of the person performing the procedure must be ensured. Inexperienced individuals should not learn how to perform procedures on fully aware children with cancer. Aggressive pharmacological treatment of the first painful procedure is often necessary to prevent the cycle of fear that emerges when a painful procedure needs to be repeatedly performed. Behavioural approaches can be integrated into the plan after the initial diagnostic procedures are completed. If using pharmacological agents which produce conscious sedation, children should be carefully observed by an individual whose sole
-175-
Manual on the prevention and control of common cancers
responsibility is monitoring the child's breathing and level of consciousness. Where available, pulse oximetry should be used to monitor the child. An individual who is skilled at airway management should be present along with resuscitative equipment and drugs.
-176-
Cancer pain relief and palliative care
References and suggested readings 1. 2. 3. 4. 5. Cancer Pain relief and palliative care. Geneva, World Health Organization, l990 (WHO Technical Report Series No. 804). Cancer pain relief. Second Edition. Geneva, World Health Organization, l996. Cancer pain relief and palliative care in children. Geneva, World Health Organization, l996. Cherny NI, Foley KM. Current approaches to the management of cancer pain: a review. Annals Academy of Medicine Singapore. l994, 33(2): l39-l57. Cleeland CS, Bruema E. Pain and symptom management. In: Love RR (ed.) Manual of clinical oncology. Sixth Edition; International Union Against Cancer; Springer-Verlag, l994: 556-569. Doyle D, Hanks GWC, MacDonald N, eds. Oxford textbook of palliative medicine. Oxford, Oxford University Press, l994. Levy MH. Pharmacologic treatment of cancer pain. New England Journal of Medicine, l996, 235 (l5): 1126. National cancer control programmes - policies and managerial guidelines. Geneva, World Health Organization, l995. Serdin RC, et al., When is pain mild, moderate or severe: grading pain severity by its interference with functions. Pain, l995, 61:277-284.
6. 7. 8. 9.
10. Sutton PM. Practical palliative care - a clinical guide. Geneva, World Health Organization, l994. 11. Symptom relief in terminal illness. Geneva, World Health Organization, l996. 12. Trump DL, Smith DL, Systemic therapies. In: Love RR, (ed.) Manual of clinical oncology. Sixth Edition. International Union Against Cancer; Springer-Verlag, l994: 202-228.
-177-
8.
Oral cancer Magnitude, cause and prevention Magnitude
I
n l990, cancers of the mouth and pharynx were ranked sixth most common and comprised 6 per cent of all cancers. They were more common among males (7.9 per cent of all cancers in males) than among females (3.9 per cent of all cancers in females). Cancers of the tongue and mouth vary widely among countries in both current incidence rates as well as time trends. They are most common among Indian populations because of the well-established association with betel-quid chewing. Indian migrant populations who retain the habit (e.g. in Singapore) retain their high rates, while those who stop the habit (e.g. in Fiji) do not. Time trends observed in other populations, and among subsets of populations, either show an increase, a decrease, or a re-increase, depending upon the levels of betelquid chewing, cigarette or pipe smoking, and alcohol consumption. Table 8 shows the 1990 estimated age-standardized incidence rates (ASR) for oral cavity and pharynx cancers in ten countries and one area in the Western Pacific Region.
Oral cancer
Table 8. Oral cavity and pharynx cancer: age-standardized incidence rates (ASR) per l00 000 in ten countries and one area in the Western Pacific Region (l990 Estimates, Reference 6). COUNTRY/AREA ASR MALES % ALL CANCERS 5.24 4.62 11.45 2.00 8.13 4.06 30.26 7.42 1.99 13.44 12.96 ASR FEMALES % ALL CANCERS 1.98 3.10 6.35 1.03 4.78 1.56 16.59 5.68 0.90 6.16 8.96
Australia China Hong Kong Japan Malaysia New Zealand Papua New Guinea Philippines Republic of Korea Singapore Viet Nam
14.66 11.61 36.70 5.34 14.60 12.13 56.40 11.30 4.22 30.32 32.40
4.75 6.37 13.9 1.76 6.9 4.47 30.88 8.08 1.35 12.18 17.07
Among males, the highest rate was in Papua New Guinea (PNG) where betel-quid chewing is widespread, and the lowest rates were in the Republic of Korea and Japan where the practice does not exist. High rates were also observed in Hong Kong and Singapore, principally among Indians, and in Viet Nam, as chewing is also prevalent in these populations. Although not as high as the three betel-quid chewing populations, rates were also higher than many countries among Chinese, Filipinos, Australians, New Zealanders and Malaysians and the causative factors may be those other than betel-quid chewing. The rates among females were two to three times lower than those seen in males, but followed the same risk pattern.
-177-
Manual on the prevention and control of common cancers
Cause Reports on the association between oral cancer and the habit of betelquid chewing date as far back as the late nineteenth century. The IARC Working Group Report (l985), after examining the accumulated data on exposure, animal experiments, and human epidemiological studies, concluded that there was sufficient evidence that the habit of chewing betel-quid containing tobacco is carcinogenic to humans. At that time the group also concluded that there was still inadequate evidence that the habit of chewing betel-quid without tobacco was carcinogenic to humans. Nevertheless, while some controversy still exists, all forms of betel-quid chewing should be discouraged. The long-term use of "smokeless" tobacco, such as in chewing tobacco quids (plugs) or using snuff, is also associated with substantially increased risk (2 to 3 times higher) of developing oral cancer. Cigarette smoking is also causally associated with oral cancer, and dose-response relationships between the number of cigarettes and oral cancer risk have also been demonstrated. There is similarly overwhelming evidence that alcohol intake increases the risk of developing cancers of the oral cavity, pharynx, larynx, oesophagus and liver, also with demonstrated dose relationships. There is no indication that the effect is dependent on the type of alcoholic beverage. The risks for these cancers are multiplied in people who smoke.
Prevention Primary prevention The most obvious and efficacious primary prevention control measure in the Region would be the elimination of betel quid/tobacco chewing and smoking habits. Some intervention studies have shown that leukoplakia, precancerous lesions, regress rapidly after the cessation of betel chewing. Education programmes which successfully reduce the prevalence of chewing and tobacco smoking also seem to reduce rates of leukoplakia incidence. Some reports estimate that three-quarters of oral cancer cases in the populations studied could have been prevented if exposure to tobacco and alcohol had not occurred.
-178-
Oral cancer
While there are still conflicting reports from animal and human studies on the protective effects of specific dietary components (micronutrients), such as specific vitamins, minerals and trace elements, there is also very strong evidence that a healthy diet protects individuals from cancers. This indicates that several dietary components from whole grains, vegetables and fruits must be present in order to inhibit carcinogenesis. Considering that many betel-quid/tobacco chewers, smokers and alcohol drinkers also have unhealthy dietary habits, the addition of measures aimed at promoting a healthy diet is an attractive complementary strategy in the primary prevention of oral cancer.
Secondary prevention - early detection The aim of early detection is to identify precancerous lesions and early stage cancers which are highly curable. The anatomical location of oral cancer provides good opportunities for early detection. While no randomized controlled trials have been reported, some screening programmes in high-risk areas have demonstrated that trained health workers are capable of accurately identifying precancerous lesions and oral cancer. While population-based screening for oral cancer cannot yet be recommended as a general public health policy for the Region, some countries with very high incidence rates may consider self-examination and/or health worker examination. The decision to do so, and whom to identify as being of highest risk, will also depend upon available resources and the other objectives of the country's cancer control programme.
-179-
Manual on the prevention and control of common cancers
The oral cancer control programme Primary prevention The incidence and mortality rate of oral cancer can be reduced by both primary and secondary prevention. Primary prevention is accomplished through tobacco control measures (see Chapter 14 - Lung cancer), and those directed against betel-quid/tobacco chewing, and excessive alcohol consumption. Alcohol control should consider two important elements. First is the wide inter-country and intra-country variability in the many social forces that affect alcohol use. Second, excessive alcohol consumption, just like the unhealthy "affluent diet", is associated with many other health problems as well as domestic, social and industrial problems. Reducing individual alcohol consumption seems to be potentially the most powerful strategy against alcohol abuse. Health education should, as in tobacco control, prioritize the vulnerable young. The main features of an alcohol control programme are summarized diagrammatically in Figure 8.1. The promotion of a healthy diet (see Chapter 16 - Breast cancer) will also contribute to the primary prevention of oral cancer.
Secondary prevention Secondary prevention of oral cancer is feasible because the oral cavity is accessible for routine examination. It has been shown in many countries that health workers can be trained to help in early detection of oral cancer and precancerous lesions. The main features of early detection of oral cancer are summarized diagrammatically in Figure 8.2.
-180-
Oral cancer
Figure 8.1: Primary prevention - alcohol
Implementation Establish collaboration with those interested in alcohol control at government and NGO level Perfrom a sampling survey to identify current alcohol consumption and pricing trends Set up a threefold strategy based on the following:
Education Promote peer-to-peer programmes for adolescents Mass education Professional education Link with other elements of a healthy lifestyle (e.g. exercise) Integrate with related messages (e.g. on road traffic accidents and family violence) Use the influence of the media
Legislation Taxation Change agricultural support to reduce alcohol production Warning labels Regulate distilling industry Legislate for non-consumption of alcohol at work and by drivers
National leadership Promote interdisciplinary and interministerial collaboration Promote domestic and international collaboration, by government, addiction foundations, and NGOs
Process measures >80% schoolchildren aged 10 years and over receive education on hazards of drinking >50% of adults see an anti-alcohol publicity message each year >2 anti-alcohol legislative measures introduced Impact measures >80% of schoolchildren aged 10 years and over aware of hazards of drinking >50% of adults aware of link between alcohol and cancer (especially among smokers) Outcome measures Short term: >50% of adults reducing their alcohol consumption Medium term: reduction in incidence of cirrhosis Long term: reduction in incidence of cancers of the head and neck, oesophagus, and liver
Source: National cancer control programmes, Geneva, WHO, 1996
-181-
Manual on the prevention and control of common cancers
Figure 8.2: Secondary prevention, downstaging for oral cancer Implementation Establish health education for awareness of the disease Educate users of tobacco to examine their mouths and the mouths of others to detect premalignant lesions Train primary health care workers to examine the mouth and identify premalignant lesions and oral cancer Ensure link between identification of abnormality and referral for diagnosis, treatment, and follow-up Establish information system for monitoring and evaluation
Detectable preclinical phase (DPCP)
Birth
Onset of sexual activity
Dysplasia
Carcinoma in situ
Invasive cancer
Death
Average age: 12 18 Examinations here unlikely to find cancers ~8% of cancers 35 Examinations here are cost-effective 45 50 years
~92% of cancers
Process measures >80% of tobacco smokers and chewers receive education on examining their own mouths >80% of primary health care workers informed of the need to examine the mouths of tobacco smokers and chewers Impact measure >80% of tobacco smokers and chewers aged 35-54 examined at least once Outcome measures Short term: >30% of oral cancers discovered by examination Medium term: >30% reduction in proportion of cases of invasive oral cancer with advanced (stage II+) disease Long term: >30% reduction in oral cancer mortality
Source: National cancer control programmes, Geneva, WHO, 1996
-182-
Oral cancer
Screening The accessibility of the oral cavity and the relative ease, affordability and acceptability of an oral examination make screening for oral cancer an attractive public health option, particularly in high incidence areas. Although no randomized trials have been completed, several screening programmes have demonstrated feasibility and success in detecting early cancer and even precancerous lesions. If efforts are to be spent in detecting oral cancer in asymptomatic individuals, concentration on high risk groups is suggested, namely those who are 40 years or older, chronic cigarette smokers, heavy alcohol drinkers and betel-quid chewers. Health education activities should be conducted at the time the oral examination is performed.
Early diagnosis and curative treatment Every person who has complaints referable to the oral cavity should have a thorough oral examination. What the normal mucosa of the oral cavity looks like is familiar to most individuals and, with appropriate training, health workers can detect areas that "do not look normal". Depending on what the lesion looks like initially, the age of the patient and associated risk factors, the suspected lesion can be observed for progression or biopsied outright. Punch biopsy of oral lesions is simple, safe and affordable, and can be performed by properly trained health workers in the clinic. The majority of oral cancer are squamous cell carcinomas. The prognosis of oral cancer depends on the clinical stage (Appendix 3). Surgery and radiotherapy are the major treatment modalities. Even large lesions (Stage III), when resectable, can result in long disease-free survival. Small lesions are curable by radiotherapy, which may be more beneficial for lesions in the tongue or in less accessible areas such as the back of the oral cavity.
Palliative treatment Distant metastases are relatively uncommon. Large lesions which cannot be completely resected (T4 lesions) continue to pose therapeutic problems. A large number of individuals still present with locally advanced cancer in developing countries and among the urban poor in developed nations. Unfortunately, combinations of surgery, radiotherapy and chemotherapy have not consistently demonstrated a benefit in both locoregional control and survival. As current multimodal therapies for
-183-
Manual on the prevention and control of common cancers
advanced oral cancer are quite expensive, prolonged, and associated with high morbidity, their use outside ethical clinical trials is not recommended. Rather, the principles and practice of cancer pain relief and palliative care should be adhered to.
What the health worker should do Health education The Core Cancer Health Education Module recommended for the Region (see Chapter 6 - Health education) includes 1) promoting cancer awareness that tobacco smoking or chewing, betel quid chewing and heavy alcohol consumption causes oral cancer, and promoting a healthy diet, and 2) persuading cigarette smokers or chewers, betel-quid chewers, and heavy alcohol drinkers to stop the habit.
Early detection Oral examination findings that should elicit a suspicion of malignacy are: • • • • • reddish plaques or patches; whitish plaques or patches; non-healing sores; bleeding in the oral cavity even with slight trauma; ulcerations;
-184-
Oral cancer
•
fungating masses (Figure 8.3); and
•
restricted opening of the mouth.
The following are the steps in an oral examination: 1. 2. Patient removes all dental prosthesis. Patient is seated upright with back rest to stabilize the head during examination. The examiner positions himself to one side of the patient. Adequate illumination is provided by a headlamp, head mirror or strong flashlight. Start by inspection of the oral cavity by area (e.g. lips, tongue, gum, cheek, hard palate, soft palate). When a suspicious lesion is seen, a bimanual examination is performed, with a gloved hand in the oral cavity and the other hand on the patient's face and neck. The finger tips of both hands are pressed simultaneously on the lesion, feeling for submucosal thickening, and assessing the size, depth and mobility of the lesion.
3. 4.
5.
6.
-185-
Manual on the prevention and control of common cancers
7.
The back of the tongue is palpated with one sweep of the finger as part of the oral examination.
The following are the steps in the examination of the neck: Examination of the neck can either be performed with the examiner behind or in front of the patient (or even alternately). 1. The patient is seated with the back straight and the shoulders level. Inspection focuses on visible masses, ulcerations, discolorations or other skin changes while making the patient swallow a few times. Palpation with the flat of the finger tips begins with the neck slightly extended, and the thyroid gland is examined for enlargement and nodularity during repeated swallowing. The neck is then slightly flexed anteriorly to examine the areas under the jaws and chin, using the finger tips and applying firm pressure against the jaw bone, encompassing the whole area from the chin to the back of the jaw bone and behind the earlobe. The neck may be extended, rotated and flexed anteriorly and laterally to relax muscles and facilitate the palpation of different areas under the jaw and the rest of the neck. Palpation then proceeds to the areas underneath, in front and behind the sternocleidomastoid muscle. The examination concludes with palpation of the supraclavicular areas.
2.
3.
4.
5.
6.
7.
The main areas of concern in a neck examination is the detection of thyroid nodules and lymph node enlargement. Many cancers spread to neck nodes with the most common being: • • oral cancer to any nodes under the jaw; nasopharynx cancer to nodes at the jaw angle, behind the earlobe and the upper portion of the sternocleidomastoid muscle; thyroid cancer to nodes in the vicinity of the middle and lower portion of the sternocleidomastoid muscle; and
•
-186-
Oral cancer
•
lung, oesophagus, stomach, supraclavicular nodes.
liver, colon and rectum cancer to
Palliative care For most patients with locally-advanced unresectable oral cancer, relief of pain and other symptoms, with social, psychological and spiritual support, should aim to improve the quality of remaining life.
-187-
Manual on the prevention and control of common cancers
References and suggested readings 1. Alcohol drinking. Lyon, International Agency for Research on Cancer, l985 (IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 44). Control of oral cancer in developing countries. Bulletin of the World Health Organization, l984, 62(6): 817-830. Eddy DM. Secondary prevention of cancer: an overview. Bulletin of the World Health Organization, l986, 64(3): 421-429. Fleming ID, Cooper JS, Henson DE, Hutter RVP, Kennedy BJ, Murphy GP, O’Sullivan B, Sabin LH, Yarbro JW (editors) AJCC Cancer Staging Manual. Fifth edition. American Joint Committee on Cancer; Lippincott-Raven, 1997. National cancer control programmes: policies and managerial guidelines, Geneva, World Health Organization, l995. Pisani P, Parkin DM, Muñoz N. Ferlay J. Cancer and infections: estimates of the attributable fraction in l990. (submitted for publication). Tobacco habits other than smoking, betel-quid and areca-nut chewing; and some related nitrosamines. Lyon, International Agency for Research on Cancer, l985 (IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 37). Tobacco smoking. Lyon, International Agency for Research on Cancer, l986 (IARC Monographs on the Evaluation of Carcinogenic Risks to Human Vol. 38). Tomatis L (editor) Cancer: causes, occurrence and control. Lyon, International Agency for Research on Cancer, l990 (IARC Scientific Publications, No. l00).
2. 3. 4.
5. 6. 7.
8.
9.
10. Tupchong L, Engin K. Tumors of the Head and Neck. In: Love RR (editor) Manual of clinical oncology. Sixth Edition. International Union Against Cancer; Springer-Verlag l994: 259-278. 11. Van Parijs LG. Public education in cancer prevention. Bulletin of the World Health Organization, l986; 64(6): 917-927.
-188-
9. Nasopharyngeal cancer Magnitude, cause and prevention Magnitude
N
asopharyngeal cancer (NPC) is generally rare, and age-standardized incidence rates are usually less than 1.0 per l00 000. South China and South-East Asia are high risk areas. The highest incidence rates are in Hong Kong (30.0 per cent in males and 12.9 per cent in females). In China the highest mortality rates are seen in south-eastern provinces near Hong Kong: Guangdong, Guangxi, Fujian and Hunan. Chinese migrants to Hong Kong and Singapore retain the differentials in risk of regions of origin. Compared to most countries worldwide, NPC is also seen more frequently in the Philippines, Viet Nam, Indonesia, Thailand and in Malay residents in Singapore. The age-specific incidence rates of NPC begin to rise in much younger people (15-29 years) compared with most other epithelial cancers. The increase with age is less steep, with little or no increase after the sixth decade. NPC risk in third-generation Chinese immigrants born in the USA is half that of first-generation migrants born in China. This strongly suggests environmental factors associated with traditional practices and exposure to a common virus at an early age in the causation of NPC.
Manual on the prevention and control of common cancers
Cause Epidemiological studies in Hong Kong have provided strong evidence that salted fish intake, and some pickled foods, particularly during the weaning period, are associated with a high risk of NPC. Another factor implicated is exposure to the Epstein-Barr virus (EBV). While EBV may also play an important role in causation, and antibody testing has been reported for early diagnosis, the evidence is not yet strong enough to recommend preventive strategies based on vaccination.
Prevention There is no primary prevention measure specific to NPC. Nevertheless, the promotion of a healthy diet, beginning in infancy, is expected to lower the incidence rate. In areas where salted fish is a traditional component of food for babies who are being weaned, mothers should be encouraged to shift to more nutritious foods.
The nasopharyngeal cancer control programme Primary prevention A potential for primary prevention could exist within Chinese ethnic groups in China and South-East Asia where the incidence of NPC is the highest, and where it has been linked to the consumption of salted fish during weaning. Primary prevention may be in the form of improving dietary habits, particularly during weaning.
- 190-
Nasopharyngeal cancer
Secondary prevention Screening There is still no recognized screening method that has been shown to reduce mortality and can be recommended as public health policy in the Region. In high risk populations, studies on population-based screening should be encouraged. In Guangdong, China, a screening programme involving a population of around l00 000 was carried out between 1986 to 1995. Increased early detection and five-year survival has been observed with some indications that mortality may be decreased.
Early diagnosis and curative treatment The early detection of nasopharyngeal cancer is difficult. Patients often consult because of metastasis to the jugulodigastric nodes in the neck. Recurrent nasal stuffiness leading to frank nasal obstruction, frequent epistaxis, earache and unilateral hearing impairment are common, but are often not taken seriously by patients and physicians. Once suspected, the patient should undergo a complete head and neck examination. He should also have triple endoscopy (nasopharyngoscopy, bronchoscopy, oesophagoscopy) with biopsy of obvious or suspicious lesions. Even if no lesion is seen, a blind nasopharyngeal biopsy should be performed on all patients with suspicious lymph nodes in the upper neck, since often the primary lesion is not evident visually. The neck node should be biopsied if no primary lesion is found. A CT scan or MRI are complimentary procedures and are not ordered routinely. The clinical staging of nasopharyngeal cancer is shown in Appendix 4. The curative treatment for nasopharyngeal cancer is radiotherapy using external radiation and brachytherapy. Cervical metastasis does not preclude radiotherapy since long-term locoregional control is still possible. Portals should include the nasopharynx and the neck. In some specialized centres, surgical resection of recurrent primary tumours has resulted in good long-term symptom control. Some recent reports describe induction or adjuvant chemotherapy as improving locoregional control, but survival is still a controversial issue.
-191-
Manual on the prevention and control of common cancers
Palliative treatment Palliation should be given for advanced disease. In such cases, local and regional control through radiotherapy is helpful. In cases of recurrence after radiation, surgery in the form of excision of the recurrence in the nasopharynx, or standard radical neck dissection for cervical node recurrence may be helpful. Relief of pain and other symptoms, with or without palliative radiotherapy and/or palliative surgery, should always be part of palliative care. Chemotherapy may be used for radiosensitization but its role in prolongation of survival is still unclear.
What the health worker should do Health education The Core Cancer Health Education Module recommended for the Region (see Chapter 6 - Health education) includes 1) increasing awareness that a healthy diet protects against many noncommunicable diseases, including cancer, and 2) persuading individuals who have unhealthy dietary habits to change to a healthy diet. In addition, in high risk areas such as those in Southern China, the practice of including salted fish in the diet of infants during weaning should be stopped.
Early detection The benefits of radiotherapy are greatest when the primary lesion and the cervical node metastasis are not yet bulky. Health workers should suspect nasopharyngeal cancer when an adult complains of recurring nasal stuffiness, epistaxis, earache or unilateral hearing impairment,
- 192-
Nasopharyngeal cancer
particularly if there are enlarged lymph nodes in the upper neck. Refer early, when possible, for diagnosis and treatment.
Palliative care When active treatment is no longer possible (i.e. radiotherapy), pain and symptom control with social, psychological and spiritual support should be given to improve the quality of remaining life.
-193-
Manual on the prevention and control of common cancers
References and suggested readings 1. Fleming ID, Cooper JS, Henson DE, Hutter RVP, Kennedy BJ, Murphy GP, O’Sullivan B, Sabin LH, Yarbro JW (editors) AJCC Cancer Staging Manual. Fifth edition. American Joint Committee on Cancer; Lippincott-Raven, 1997. National cancer control programmes: policies and managerial guidelines. Geneva, World Health Organization, 1995. Tomatis L (editor) Cancer: causes, occurrence and control. Lyon, International Agency for Research on Cancer, 1990 (IARC Scientific Publications, No. 100). Tupchong L, Engin K. Tumors of the Head Neck. In: Love RR (editor) Manual of clinical oncology. Sixth Edition. International Union Against Cancer; Springer-Verlag 1994: 310-329.
2. 3.
4.
- 194-
10. Oesophageal cancer Magnitude, cause and prevention Magnitude
I
n 1980, oesophageal cancer was estimated to rank as the seventh most common cancer worldwide and would have comprised almost five per cent of all cases. The incidence rate among males is generally double that of females. The cancer occurs less frequently in developed countries, where it was ranked fifteenth, than in developing countries where it was the fourth most common. Incidence rates vary widely between countries, and in some countries also between ethnic populations or regional distributions. Over half of the total annual cases in the world occur in China. Migrants from high-risk to low-risk areas eventually attain the same risk level as long-time residents of the country of migration, indicating the important role of environmental agents. In some Caucasian populations a decreasing incidence had been associated with decreasing alcohol consumption. In South Africa, increasing incidence has been linked to increasing alcohol consumption. Declining rates in Linxian county in China are probably greatly influenced by improved nutrition.
Manual on the prevention and control of common cancers
Table 10 shows the 1990 estimated incidence rates in ten countries and one area of the Western Pacific Region. Table 10. Oesophageal cancer: age-standardized incidence rates (ASR) per l00 000 in ten countries and one area in the Western Pacific Region (l990 Estimates, Reference 6). COUNTRY/AREA ASR MALES % ALL CANCERS 2.05 13.33 5.59 2.67 2.19 3.39 1.88 1.56 3.82 4.60 2.12 ASR FEMALES % ALL CANCERS 0.82 7.82 l.69 1.32 1.03 0.93 1.73 0.91 0.96 1.62 0.80
Australia China Hong Kong Malaysia New Zealand Japan Papua New Guinea Philippines Republic of Korea Singapore Viet Nam
5.72 33.49 17.90 4.80 6.54 9.04 3.50 2.38 8.08 10.38 5.30
1.97 16.06 3.70 1.90 2.94 1.59 3.22 1.30 1.43 3.20 1.53
Among males, the rate in China was far higher than the rest, followed by Hong Kong, Singapore, Japan and the Republic of Korea where the rates were about a third of that in China. The lowest rates were in the Philippines and Papua New Guinea. The incidence rate was lower among females in China, being half of the rate in males. The rates for females in the other countries were similar, and were about a sixth of that observed in Chinese females.
Cause
-196-
Oesophageal cancer
The most common histological type of oesophageal cancer is squamous carcinoma. The presence of "oesophageal cancer belts", wide inter-country and intra-country incidence variability and marked changes in incidence among migrant populations, strongly indicate a major role for environmental factors in the causation of oesophageal cancer. In many populations in high-incidence non-Asian countries the evidence for the role of alcohol is strong. Clear dose-response relationships have been observed with the amount of alcohol consumed daily. Risks are multiplied in heavy drinkers who are also heavy smokers. Several correlation studies have provided indirect evidence that exposure to high levels of nitrates and nitrites in food and drinking water increase the risk for stomach and oesophageal cancer. The drinking of hot beverages in general, frequently practiced in populations with very high incidence, has been associated with increased risk. The risk of oesophageal cancer is also increased among smokers, and a dose-response relationship has been reported. A theme common to the many analytical studies on oesophageal cancer is its association with poverty and a restricted diet. Regardless of whether the carcinogenic agent is alcohol, tobacco, nitrates and nitrites, salty and pickled foods or hot beverages, an underlying chronic deficiency in the intake of fruits and vegetables, which contain micronutrients that are known to protect against cancer, is present in high-risk populations. In some Western countries with a high prevalence of chronic reflux oesophagitis, the incidence of adenocarcinoma of the oesophagus has increased and may even be higher than squamous carcinoma.
Prevention The potentials for primary prevention of oesophageal cancer are great, as many primary public health measures aimed at promoting health and preventing many important diseases, such as tobacco control, alcohol control and promotion of a healthy diet, are expected to also lower the incidence of oesophageal cancer. Reports on populations where cigarette smoking and alcohol consumption has decreased, either singly or in combination, show a decrease in oesophageal cancer incidence. Populations whose diets have improved, including migrant populations, also demonstrate decreasing incidence.
-197-
Manual on the prevention and control of common cancers
No practical screening method is available for large scale early detection.
The oesophageal cancer control programme Primary prevention Three public health measures which are very important in general health promotion and in the prevention of many other diseases also lower the risk of oesophagus cancer. They are tobacco control (see Chapter 14 Lung cancer), alcohol control (see Chapter 8 - Oral cancer) and the promotion of a healthy diet (see Chapter 16 -Breast cancer).
Secondary prevention - early detection Screening There is at present no effective method that can be recommended for population-based screening for oesophageal cancer.
Early diagnosis and curative treatment Staging of oesophageal cancer is shown in Appendix 5. During the early stages (I, II) when the tumour is still small, cancer of the oesophagus is usually asymptomatic. In the large majority of cases, dysphagia is the presenting symptom and, unfortunately, this occurs when significant obstruction is caused by a large tumour. The most important prognostic factor is the presence or absence of spread to the regional lymph nodes, which can only be determined with certainty from a surgical specimen. The overall actuarial five-year survival of node-negative cases ranges from 40-60 per cent and drops significantly for node-positive cases, ranging from 10-30 per cent
-198-
Oesophageal cancer
Progressive dysphagia and weight loss in an adult should always elicit suspicion. A large number of patients are still amenable to palliative, and even curative surgery, if the diagnosis is made soon after dysphagia begins. The diagnosis of patients suspected of having oesophageal cancer is established by contrast radiologic examination, (barium swallow) with or without fluoroscopy, and/or oesophagoscopy with biopsy. Surgical resection remains the main modality of curative and palliative treatment for oesophageal cancer, and patients deemed operable should have the benefit of surgery. Resectability ranges from 50-85 per cent. Randomized clinical trials, using combinations of surgery, radiotherapy and systemic chemotherapy, have been reported to result in improved survival, but there is still no consensus and no definite guidelines have emerged.
Palliative treatment An obstructed oesophagus is accompanied by tremendous physical and psychological suffering. Inability to eat deprives an individual of a primal and universal source of satisfaction. Repeated aspiration of saliva adds to the suffering. Surgery is still the most effective method of palliative therapy, consisting of resection or by-pass of the primary tumour. For the inoperable patient, several methods may be used for palliation. The insertion of long, firm plastic tubes through the tumour (Celestin tube stents) may restore eating but this is associated with tube migration or reobstruction with food or tumour. Laser vaporization of intraluminal obstructing tumours has been tried, but regrowth of the tumours, scar formation and tumour perforation are factors limiting its use. A recent variant of laser therapy is photodynamic therapy. Dihematoporphyryn is injected intravenously and the dye is selectively retained by the tumour which is destroyed when exposed to laser after 24 hours. Other palliative modalities such as radiation (external beam or brachytherapy) alone or in combination with systemic chemotherapy have been employed but recurrence of the obstruction is quite fast.
-199-
Manual on the prevention and control of common cancers
What the health worker should do Health education The Core Cancer Health Education Module recommended for the Region (see Chapter 6 - Health education) includes 1) increasing awareness that cigarette smoking, excessive alcohol consumption and an unhealthy diet cause many noncommunicable diseases, including cancer, and a healthy diet protects against cancer, and 2) persuading individuals who smoke, drink alcoholic beverages excessively and have unhealthy dietary habits to give up these cancer-causing lifestyles.
Early detection Oesophageal cancer should be suspected when an adult complains of progressive dysphagia and weight loss. Refer early for diagnosis and treatment whenever possible.
Palliative care When active intervention measures (e.g. surgery, tube stent, radiotherapy) are not feasible or available, pain and symptom control with social, psychological and spiritual support should be given in order to improve the quality of remaining life.
-200-
Oesophageal cancer
References and suggested readings 1. Alcohol drinking. Lyon, International Agency for Research on Cancer, l985 (IARC Monographs on the Evaluation of Carcinogenic Risk to Human, Volume 44). Diet, nutrition, and the prevention of chronic diseases. Geneva, World Health Organization, l990 (Technical Report, Series 797). Eddy DM, Secondary prevention of cancer: an overview. Bulletin of the World Health Organization, l986, 64(3): 421-429. Fleming ID, Cooper JS, Henson DE, Hutter RVP, Kennedy BJ, Murphy GP, O’Sullivan B, Sabin LH, Yarbro JW (editors) AJCC Cancer Staging Manual. Fifth edition. American Joint Committee on Cancer; Lippincott-Raven, 1977. National cancer control programmes: policies and managerial guidelines. Geneva, World Health Organization, l995. Pisani P, Parkin DM, Muñoz N, Ferlay J. Cancer and infection: estimates of the attributable fraction in l990. (submitted for publication). Sherman JR CB, Caldwell CB, Kim JP. Cancer of the Esophagus and Stomach. In: Love RR (editor) Manual of clinical oncology. Sixth Edition. International Union Against Cancer; Springer-Verlag l994: 310-329. Tobacco smoking. Lyon, International Agency for Research on Cancer, l986 (IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Vol. 38). Tomatis L (editor) Cancer: causes, occurrence and control. Lyon, International Agency for Research on Cancer, l990 (IARC Scientific Publications, No. l00).
2. 3. 4.
5. 6. 7.
8.
9.
10. Van Parijs LG. Public Education in Cancer Prevention. Bulletin of the World Health Organization, l986, 64(6): 917-927. 11. World Progress in Surgery - Current Issues in the Management of Squamous Esophageal Carcinoma. World Journal of Surgery, l994, 18(3). 12. World Progress in Surgery - Multimodal Treatment and Prognostic Factors in GI Cancer. World Journal of Surgery, l995, 19(2).
-201-
11.
Stomach cancer
Magnitude, cause and prevention Magnitude
S
tomach cancer has now been overtaken by lung cancer, but in l980 it was the most common cancer and comprised l0.5 per cent of total cancers. Incidence rates in males were roughly double those in females, and total cases then were about equal in developed and developing countries. There are wide variations in rates between countries, and the highest rates occur in Japan. There is now an almost universal decline in the incidence of stomach cancer. The decline has been occurring steadily but rather slowly, and there is also wide inter-country variation in the rate of decline. The decline in Japan has been less marked than elsewhere. The change in incidence among migrants is also slow. Table 11 shows the 1990 estimated agestandardized incidence rates (ASR) in ten countries and one area of the Western Pacific Region. Among males, the rates were highest in Japan, the Republic of Korea and China. The rates were lowest in Fiji, Papua New Guinea, the Philippines, Australia and New Zealand. Intermediate rates were estimated for Singapore, Viet Nam, Hong Kong and Malaysia. Among females, the rates were about half of those estimated for males, and followed a similar location ranking.
Stomach cancer
Table 11. Stomach cancer: age-standardized incidence rates (ASR) per l00 000 in ten countries and one area in the Western Pacific Region (l990 Estimates, Reference 4). COUNTRY/AREA ASR MALES % ALL CANCERS 3.33 20.13 6.72 29.45 9.75 3.66 5.08 5.87 29.36 12.66 3.33 ASR FEMALES % ALL CANCERS 1.97 12.50 5.21 20.75 6.58 1.47 2.32 4.35 18.62 7.22 1.97
Australia China Hong Kong Japan Malaysia New Zealand Papua New Guinea Philippines Republic of Korea Singapore Viet Nam
9.31 50.57 21.50 78.41 17.50 10.93 9.46 8.94 62.19 28.54 31.70
4.72 25.67 11.40 35.52 9.50 5.62 4.31 6.19 27.66 14.28 4.72
Cause The factors involved in the causation of stomach cancer are not as clear as for other cancers. Many components of the human diet, including drinking water, contain nitrites and nitrates which can react with other substances in the stomach to produce compounds that are carcinogenic to experimental animals. Some studies have provided indirect evidence that exposure to high levels of nitrites and nitrates increase the risk of stomach and oesophageal cancer. Salt and salty foods have also been reported to increase the risk of stomach cancer, and some theories postulate that the combined effects of chronic irritation by excess salt and the high nitrite and nitrate contents of salt-preserved foods could be to blame.
-203-
Manual on the prevention and control of common cancers
There is also accumulating evidence that Helicobacter pylori infection also increases the risk of stomach cancer. It has been shown that H. pylori causes a chronic gastritis that has been intractable with anti-ulcer therapy. It has also been shown that treating these cases with antimicrobials, efficacious against H. pylori, has resulted in healing the chronic gastritis. It has been hypothesized that H. pylori-induced chronic gastritis, if untreated, leads to mucosal hyperplasia, then dysplasia and eventually carcinoma. There is a growing body of evidence that a high consumption of vegetables and fruits lowers the risk for cancers of the nasopharynx and larynx, oesophagus, stomach, colon, rectum, lung and breast.
Prevention There is no primary prevention measure specific to stomach cancer, although the promotion of a healthy diet, which should be a top public health priority in health promotion and disease prevention, is expected to also decrease the risk of stomach cancer. The benefits of radiologic screening for stomach cancer have been well established in Japan, but the methods are difficult and costly.
The stomach cancer control programme Primary prevention While a primary prevention method for stomach cancer cannot be as dramatic as tobacco control for lung cancer, a large number of stomach cancers can be prevented by promoting a healthy diet (see Chapter 16 Breast cancer). Important components of the healthy diet that will lower the incidence of stomach cancer are the avoidance of heavy and prolonged consumption of highly salted, pickled and smoked foods, and a concomitant increased intake of vegetables and fruits.
-204-
Stomach cancer
Secondary prevention - early detection Screening In countries where the incidence of the disease is very high (e.g. Japan) a special contrast radiographic technique, double contrast upper gastrointestinal series (UGIS), may be useful in screening for stomach cancer. Uncontrolled mass screening programmes in Japan (more than three million people each year) have demonstrated a shift in stage with early detection, an increase in five-year survival and a reduction in the risk of death in screened patients. To date, however, no randomized controlled trials have been completed and, because of the complexity and cost, its use as a screening tool cannot be recommended as policy for countries where the screening method is not yet in place.
Early diagnosis and curative treatment There are no specific signs or symptoms of early stomach cancer but symptoms similar to those of a peptic ulcer may be present. Common signs, all suggestive of advanced disease, are epigastric mass, weight loss and an enlarged liver. Dysphagia (in the patient with cancer at the cardia) and vomiting (in the patient with pyloric or prepyloric cancer) may be present at an earlier stage. There should be a high index of suspicion for stomach cancer among individuals who are 40 years old or older who manifest with recurrent epigastric discomfort (often with several courses of anti-ulcer treatment), fullness, pain, and unexplained indigestion. Such patients should undergo endoscopy. Doubled-contrast UGIS, fluoroscopy and endoscopy with multiple biopsies are the usual studies used to confirm the diagnosis of stomach cancer. In Japan, experienced radiologists use fluoroscopy with 90-95 per cent accuracy in diagnosing early gastric carcinoma. If biopsy and cytology studies are non-diagnostic and the clinical suspicion for cancer is high, repeated biopsies are necessary. The staging system for stomach cancer at present utilizes the l992 TNM system, which incorporates some important elements in staging from the Japanese system (Appendix 6). The two critical elements in prognosis are the depth of the penetration of the tumour through the stomach wall and the involvement by the cancer of increasing echelons of lymph nodes (primary, secondary and tertiary drainage nodes). The primary drainage nodes (i.e. within 3 cms) are different for different parts of the stomach.
-205-
Manual on the prevention and control of common cancers
Radical surgery, usually subtotal or total gastrectomy, is the only curative treatment for stomach cancer. When adjacent organs are involved, extended surgery is appropriate and may be curative if all disease can be removed. For a quarter of a century, many surgeons were reluctant to do total gastrectomies unless it was absolutely essential to resect gross disease, and they had little enthusiasm for the extensive lymph node dissection advocated by the Japanese. Recent reports however, have shown improvement in mortality, morbidity and survival with the Japanese approach and are leading to a re-evaluation of the concepts of optimal surgery for stomach cancer. To date, adjuvant radiation and/or systemic chemotherapy have had minimal, if any, favourable impact on survival in stomach cancer cases.
Palliative treatment Palliation of stomach cancer falls into three general categories: palliation of distressing symptoms, prevention of symptoms that will develop without treatment, and prolongation of a useful and comfortable life. Effective surgical palliation can be achieved for obstruction, bleeding and perforation. Relief of obstruction at the cardia or pyloroantral areas can be accomplished by resection or bypass. Another approach, if available and feasible, is endoscopic v aporization of obstructing lesions with laser therapy.
What the health worker should do Health education The following should be the health education content for the prevention of stomach cancer:
-206-
Stomach cancer
- avoid prolonged and heavy consumption of salted, smoked and pickled foods - eat a healthy diet, rich in fruits and vegetables
Early detection Stomach cancer should be suspected when an adult complains of recurrent epigastric discomfort (particularly after repeated courses of antiulcer medication), vomiting, unexplained anaemia and weight loss. There should be early referral, when possible, for diagnosis and treatment.
Palliative care When active intervention measures (e.g. surgery, laser therapy) are not feasible or available, pain and symptom control, with social, psychological and spiritual support should be given in order to improve the quality of remaining life.
-207-
Manual on the prevention and control of common cancers
References and suggested readings 1. 2. Eddy DM. Secondary prevention of cancer: an overview. Bulletin of the World Health Organization, l986, 64(3): 421-429. Fleming ID, Cooper JS, Henson DE, Hutter RVP, Kennedy BJ, Murphy GP, O’Sullivan B, Sabin LH, Yarbro JW (editors) AJCC Cancer Staging Manual. Fifth edition. American Joint Committee on Cancer; Lippincott-Raven, 1997. National control programmes: policies and managerial guidelines. Geneva, World Health Organization, 1995. Pisani P, Parkin DM, Muñoz N, Ferlay J. Cancer and infection: estimates of the attributable fraction in l990. (submitted for publication). Sherman Jr CB, Caldwell CB, Kim JP. Cancer of the esophagus and stomach. In: Love RR (editor) Manual of clinical oncology. Sixth Edition. International Union Against Cancer; Springer-Verlag, l994: 310-329. Tomatis L. (editor). Cancer: causes, occurrence and control. Lyon, International Agency for Research on Cancer, l990 (IARC Scientific Publications no. l00). Van Parijs LG. Public Education in Cancer Prevention. Bulletin of the World Health Organization, 1986, 64(6): 917-927. World Progress in Surgery - What's New in Gastric Cancer? World Journal of Surgery, 1995, 19(4). World Progress in Surgery - Multimodal Treatment and Prognostic Factors in GI Cancer. World Journal of Surgery, 1995, 19(2).
3. 4. 5.
6.
7. 8. 9.
-208-
12.
Colonic and rectal cancer
Magnitude, cause and prevention Magnitude
C
olonic and rectal cancers were ranked fourth most common in l980 and comprised nine per cent of all cancers. Both have been called the cancers of affluent developed countries, b eing then ranked in these areas second only to lung cancer and with double the number of cases found in developing countries, where they ranked eighth. Incidence rates for rectal cancer are generally lower than those for colonic cancer. Mortality from rectal cancer is also lower, and may be attributed to earlier detection and improved results of therapy. Migrant studies suggest environmental factors play a major role, as the rates among migrants who move from low-risk to high-risk areas approximate the rates observed in the countries of migration. Table 12 shows the 1990 estimated age-standardized incidence rates (ASR) in ten countries and one area of the Western Pacific Region. Among males, the highest rates were estimated for New Zealand, Australia, Japan, and Hong Kong, while the lowest were in the Republic of Korea and Papua New Guinea. Intermediate rates were estimated for Singapore, Viet Nam, China and Malaysia. Among females, estimated rates were generally slightly lower than those for males, and followed the same ranking.
Manual on the prevention and control of common cancers
Table 12. Colon and Rectum Cancer: age-standardized incidence rates (ASR) per l00 000 in ten countries and one area in the Western Pacific Region (l990 Estimates, Reference 4). COUNTRY/AREA ASR MALES % ALL CANCERS 14.08 6.40 10.63 13.00 12.42 15.36 5.85 8.29 4.18 10.44 7.20 ASR FEMALES % ALL CANCERS 13.03 6.45 12.07 5.12 12.74 13.39 2.24 6.59 4.21 10.68 6.15
Australia China Hong Kong Japan Malaysia New Zealand Papua New Guinea Philippines Republic of Korea Singapore Viet Nam
39.40 16.09 34.00 34.62 22.30 5.86 10.91 12.63 8.85 23.54 18.00
31.26 13.25 26.40 25.89 18.40 38.27 4.17 9.38 6.26 21.11 11.71
Cause The main dietary factors implicated in colonic and rectal cancer are fat and fibre. Correlation studies of incidence and mortality from colonic cancer in different populations have shown a strong association with average per capita consumption of fat, particularly saturated fat. However, subsequent case-control and cohort studies have had variable results. Part of the difficulty is in the inherent limitations of current dietary assessment methods. Secondary bile acids have been shown to increase cancer yields in some animal experiments, and these acids are increased when there is an increase in the number of anaerobic bacteria which metabolize primary bile acids into secondary bile acids. It has been postulated that high fat diets -210-
Colonic and rectal cancer
modify bacterial flora directly, or indirectly, by increasing biliary secretion of acids and neutral steroids. Although dietary fibre can protect from large-bowel carcinogenesis in experimental animals, its exact role in the causation of colonic and rectal cancers is still unclear, as high fibre diets are generally also high in protective micronutrients such as those contained in whole grains, vegetables and fruits. Colonic and rectal cancer risk levels are lowered by the protective effect of a diet rich in vegetables, fruits and whole grains.
Prevention There is no primary prevention measure specific to colonic and rectal cancer, but there is good reason to expect that risk levels in a population will decline after a widespread shift to a healthy diet. No population-based screening method can yet be recommended as a worldwide public health policy. Screening of faecal blood has not yet been shown to reduce mortality.
The colonic and rectal cancer control programme Primary prevention Like stomach cancer, the incidence of colonic and rectal cancer can be decreased by primary prevention, specifically by promoting a healthy diet (see Chapter 16 - Breast cancer). Important components of the healthy diet that will lower the incidence of colonic and rectal cancers are the decrease in fat consumption and the consumption of whole grain cereals and breads, vegetables and fruits. The following guidelines are suggested for the primary prevention of colonic and rectal cancer in average and high risk individuals.
-211-
Manual on the prevention and control of common cancers
•
Fat consumption should be low (both animal and vegetable) not exceeding 20 per cent of total caloric intake. Both animal and vegetable fat intake should be reduced. A balanced diet should be consumed, which includes at least 5 to 8 daily servings of fruits, vegetables, legumes, and whole grain cereals and breads in order to provide adequate fibre, vitamins and other components with anticarcinogenic effects. Dietary fibre from all sources should be at least 25 gms/day. The consumption of excess calories and being overweight should be avoided. Tobacco use should be avoided. Physical activities and exercise should be part of daily routine.
•
• • • •
Secondary prevention Screening There is some evidence that secondary prevention may be effectively carried out by means of testing for faecal occult blood and sigmoidoscopy. There is still, however, not enough evidence to recommend population screening.
Early diagnosis and curative treatment Colorectal cancer is suspected in the presence of rectal bleeding, changes in character of stools, unexplained anaemia, signs of obstruction or a palpable rectal or abdominal mass. The location of the lesion is established by means of proctosigmoidoscopy or colonoscopy, coupled with a barium enema. Although endoscopy and biopsy is highly desirable, its unavailability does not preclude surgery, especially in the presence of obstruction, a palpable rectal or abdominal mass or a mass lesion demonstrated through barium enema. A chest X-ray and liver ultrasonography or CT scan are important in order to determine the presence, number and location of lung or liver metastases. Other diagnostic examinations will depend on specific symptoms.
-212-
Colonic and rectal cancer
The prognosis for colorectal cancers is influenced greatly by the clinical stage (Appendix 7), which is determined mainly by the depth of tumour penetration of the bowel wall, and the presence of regional lymph node spread. Radical surgical resection is the main treatment, and is curative for node-negative colonic cancer (TNM I, II, or Dukes A, B). Around three quarters of patients are expected to survive at least five years, and no form of adjuvant treatment has been shown to provide a survival benefit. The probability of surviving five years following surgery for patients with node-positive colonic cancer (TNM III or Dukes C) drops to less than 50 per cent. Adjuvant treatment with 5 -FU and levamisole confers a survival benefit of 25-30 per cent on patients who either had surgery alone, or surgery plus levamisole. For rectal cancer, patients whose tumours have penetrated beyond the bowel wall (TNM II, or Dukes B) or with positive nodes (TNM III or Dukes C) have been shown to benefit from adjuvant radiotherapy, plus 5-FU, in the form of increased survival and decreased local recurrence.
Palliative treatment For physically fit individuals, surgical resection is the most effective active palliative treatment. Resection of solitary liver or lung metastasis also offers both palliation and survival benefits. Nevertheless, for the many patients for whom surgery is not possible, cancer pain relief and palliative care can in most cases improve the quality of life.
-213-
Manual on the prevention and control of common cancers
What the health worker should do Health education The health education contents for the prevention of colonic and rectal cancer are: • Decrease dietary fat, which should not exceed 20 per cent of total caloric intake. Eat a healthy diet, with plenty of whole grain cereals and breads, fruits, vegetables and legumes. Avoid being overweight. Increase regular physical activity and exercise. Stop smoking.
•
• • •
Early detection There is still no screening method that has been shown to decrease mortality. For symptomatic individuals of 50 years and older, or younger high-risk individuals (i.e. family history, colorectal polyps, inflammatory bowel disease), a digital rectal examination (DRE) should be done. A negative DRE, however, does not eliminate the possibility of cancer and the patient should be referred for additional investigations.
The following are the steps in a digital rectal examination: • The patient lies on his side with buttocks protruding near the edge of the examination table. The buttocks are spread laterally to inspect the anal opening. Obvious masses, bleeding, and abscess should be noted.
-214-
Colonic and rectal cancer
•
Palpation is done using a well lubricated gloved finger, starting at the peri-anal area and slowly inserted into the anal canal. Allow the patient to relax and accommodate the gloved finger. The finger is further advanced, palpating circumferentially for masses, tender areas and areas of narrowing, and anteriorly (prostate in males, uterus in females). The anal sphincter tone is likewise noted. The finger is examined for blood after it is withdrawn.
•
•
Palliative care For the many patients suffering with advanced colonic and rectal cancer in whom active anti-cancer treatment is neither indicated nor possible, relief of pain and other symptoms, and social, psychological and spiritual support should be given in order to improve the quality of remaining life.
-215-
Manual on the prevention and control of common cancers
References and suggested readings 1. 2. Eddy DM. Secondary prevention of cancer: an overview. Bulletin of the World Health Organization, l986, 64(3): 421-429. Fleming ID, Cooper JS, Henson DE, Hutter RVP, Kennedy BJ, Murphy GP, O’Sullivan B, Sabin LH, Yarbro JW (editors ) AJCC Cancer Staging Manual. Fifth edition. American Joint Committee on Cancer; Lippincott-Raven, 1997. National cancer control programmes: policies and managerial guidelines. Geneva, World Health Organization, l995. Pisani P, Parkin DM, Muñoz, Ferlay J. Cancer and infection: estimates of the attributable fraction in l990. (submitted for publication). Roedinger WEW. Cancer of the Colon, Rectum and Anus. In: Love RR (editor) Manual of clinical oncology. Sixth Edition. International Union Against Cancer; Springer-Verlag, l994: 336-437. Steale G Jr. Adjuvant therapy for patients with colorectal cancer. World Journal of Surgery. l995, 19(2): 240-245. Tomatis L (editor) Cancer: causes, occurrence and control. Lyon, International Agency for Research on Cancer, l990 (IARC Scientific Publications, No. l00). Van Parijs L.G. Public education in cancer prevention. Bulletin of the World Health Organization, l986, 64(6): 917-927. Winawer SJ, St. John DJ, Bond JH et al. Prevention of colorectal cancer: guidelines based on new data. Bulletin of the World Health Organization, l995, 73(1): 7-10.
3. 4. 5.
6. 7. 8. 9.
-216-
13.
Liver cancer
Magnitude, cause and prevention Magnitude
I
n 1980, liver cancer was the eighth most common cancer worldwide, comprising 4.0 per cent of all cancers. It was ranked seventh in developing countries, where there were four times as many cases compared with developed countries, where liver cancer was ranked fourteenth. Incidence rates were higher among males, with a ratio of about 3:1. Threequarters of cases occur in developing countries, and closely correlate with the prevalence of chronic carriers of hepatitis B. Variations in incidence rates within several countries in Africa and Asia have also been shown to be correlated with local aflatoxin levels in foodstuffs. The great majority of primary liver cancers that occur in areas with a high prevalence of hepatitis B virus (HBV), particularly the carrier state, are hepatocellular carcinomas (HCC). Table 13.1 shows the 1990 estimated age-standardized incidence rates (ASR) for liver cancer in ten countries and one area in the Western Pacific Region. The lowest rates were in Australia and New Zealand, where liver cancer comprised less than one per cent of all cancers among males and females. The rates among males in seven other countries were high. In Singapore, the rate in males was three times the rates in Australia and New Zealand, but about one quarter to one fifth of that seen in China, Hong Kong, Japan, the Republic of Korea, Papua New Guinea, the Philippines and Viet Nam. Rates among females were lower, from around half to a quarter of those observed among males.
Manual on the prevention and control of common cancers
Table 13.1. Liver cancer: age-standardized incidence rates (ASR) per 100 000 in ten countries and one area in the Western Pacific Region (1990 Estimates, Reference 4). COUNTRY/AREA ASR MALES % ALL CANCERS 0.95 14.74 12.01 10.78 9.97 0.93 13.71 17.75 15.87 3.20 11.61 ASR FEMALES % ALL CANCERS 0.41 7.41 4.43 4.38 4.22 0.41 6.03 6.59 6.13 11.47 4.15
Australia China Hong Kong Japan Malaysia New Zealand Papua New Guinea Philippines Republic of Korea Singapore Viet Nam
2.65 37.03 38.40 28.70 17.90 2.77 25.55 27.03 33.61 7.22 29.03
0.98 15.21 9.70 7.49 6.10 1.17 11.22 9.37 9.11 2.9 7.90
Cause Several epidemiological studies and laboratory investigations have established a strong and specific association between chronically active forms of HBV infection and HCC. This is characterized by the presence of HBV surface antigen (HBsAg) in serum, also referred to as HBV carrier state. Cohort studies have shown that the incidence of HCC among HBsAg carriers was seven to over a hundred times higher than among non-carrier control populations. The estimated relative risks are among the highest observed in cancer etiology (Table 13.2). Laboratory investigations have shown that HBV can be integrated into the genome of liver-cell lines of HBsAg carriers. All the evidence indicates a causal association. The ultimate proof of causality will be the demonstration that the elimination of HBV infection by vaccination -218-
Liver cancer
prevents HCC. In countries like Japan where HBV-induced hepatitis prevalence has decreased, hepatitis C virus (HCV) infection is now the dominant risk factor for HCC. Table 13.2. Cohort studies of carriers of hepatitis B surface antigen (HBsAg) and hepatocellular carcinoma (HCC) (Reference 3) Population No. of subje cts HCC riska Attributabl e risk (%) Reference
Total Japan 32 177
HBsAg+ 496
RR (95% CI) l0.4 (5.019.1) 6.6 (4.010.2) 9.7 (2.028.4) 12.7 lijima etal. (l984) Oshima et al (l984) Prince & Alcabes (l982) Hall et al. (l985)
Japan, Osaka
-
8646
10.1b
USA, New York City
-
6850
l.0c
England & Wales a b c
-
3934
42.0 (14.0100.0)
4.0c
RR, relative risk; Cl, confidence interval On the basis of a prevalence of HBsAG in the general population of 2.0 per cent On the basis of a prevalence of HBsAG in the general population of 0.1 per cent
Prevention There is no globally practical method of secondary prevention (early detection) for HCC which, like lung cancer, is usually fatal and accompanied by tremendous suffering. The best control measure is through primary prevention. Several safe and effective vaccines against HBV have been developed and are currently used in both large scale trials and in vaccination campaigns in many countries with high or intermediate incidence rates. Most HBV infections occur early in life and maternal transmission is important. The risk of HCC is also higher the earlier in life the HBV carrier state occurs. This indicates that mass vaccination programmes should be aimed at all infants from high-risk populations, followed by booster doses at 12 months to increase the prevalence of immune individuals.
-219-
Manual on the prevention and control of common cancers
Blood for transfusion should be routinely tested for HBV. In countries with a high prevalence of HCV, blood donors and donated blood should also be tested for HCV.
The liver cancer control programme Primary prevention Control of liver cancer should focus on primary prevention, specifically in decreasing the prevalence of the carrier state of hepatitis B infection through HBV vaccination, which should be incorporated into a country's Expanded Programme on Immunization (EPI). The main features of an HBV vaccination programme are summarized diagrammatically in Figure 13.
Secondary prevention - early detection Screening Attempts have been made to screen populations for liver cancer, particularly in China and Japan. Serological tests on children and adults identified carriers (i.e. those who are HBsAG positive) who had more than a 100-fold increase in risk. The HBV carrier population were then tested annually or bi-annually for the tumour marker alphafetoprotein (AFP), combined with utlrasonography of the liver, raised titres suggesting hepatocellular carcinoma. Many tumours detected by such screening programmes were small enough to be treated with curative surgery or other local forms of treatment, and have been associated with decreased mortality. To date, no randomized controlled trials have been completed and it cannot be recommended as a public health policy for countries where such programmes are not yet present.
-220-
Liver cancer
Figure 13. Primary prevention - viral hepatitis B
Implementation Establish collaboration with those interested in hepatitis control at government and NGO level Perform a sampling survey to identify current carrier rate and mode of transmission (horizontal or vertical) Set up HBV vaccination strategy if HBV carrier rate >10% of adults Set up a threefold strategy based on the following:
Education Mass education on need for and effectiveness of HBV vaccination Education of parents on need to vaccinate children early Education on high-risk groups (e.g. medical professionals) about vaccination
Legislation Integrate with other vaccination programmes (e.g. EPI) Standardization of biological effectiveness of vaccines Free vaccination
National leadership Promote interdisciplinary and interministerial collaboration Promote domestic and international collaboration, especially at the public health department level
Process measures >70% of adults of parental age receive educational message about vaccination against HBV >80% of primary health workers receive educational message about HBV vaccination Impact measures HBV vaccination incorporated into EPI >70% of children under 1 year of age vaccinated against HBV Outcome measures Short term: none Medium term: reduction in incidence of viral hepatitis B reduction in HBV carriers to <10% of adults Long term: reduction in incidence of primary liver cancer
Source: National cancer control programmes, Geneva, WHO, 1996.
-221-
Manual on the prevention and control of common cancers
Early diagnosis and curative treatment The great majority of early HCC cases are asymptomatic and most early cases are detected only through screening programmes as described. Among symptomatic cases, less than 5 per cent will be suitable for a curative procedure (i.e. surgical resection). Clinical staging of liver cancer is shown in Appendix 8. The most specific laboratory indicator of hepatocellular carcinomas is an AFP level greater than 400 mg/ml, which is present in more than 70 per cent of cases. Liver function tests are abnormal in varying degrees but they are not helpful in the presence of cirrhosis and chronic hepatitis. A diagnosis of hepatocellular carcinoma is further supported by imaging techniques such as ultrasonography and, if available, CT scans and arteriography. The diagnosis is confirmed by histological examination of tissue obtained by image-guided or laparoscopically-guided needle biopsy. Resectability is initially determined through the use of ultrasound which can detect patients with contraindications for curative surgery, saving as much as 60 per cent of patients the discomfort of further investigation. Patients who appear to have resectable lesions are then subjected to more sophisticated imaging procedures before surgery is finally decided upon. Surgical resection is the only curative measure available for hepatocellular carcinomas. This can be safely performed when the tumour is localized in the liver. The extent of resection depends on the extent of the tumour and usually the severity of the cirrhosis. Operations may vary from simple wedge excision to formal hepatic lobectomy or extended lobectomy. Unfortunately only 10-15 per cent of patients have resectable tumours. Chemotherapy, either systemic or through intrahepatic arterial infusion, and total hepatectomy with liver transplantation has been tried but has shown no significant impact on the survival of most patients.
-222-
Liver cancer
Palliative treatment The majority of liver cancers are in advanced stages at the time of presentation, with patients surviving less than six months. For these unfortunate patients, palliation is the primary objective of treatment. Pain should be relieved, pleural effusion drained, ascites controlled and anxiety reduced. The most important aim of therapy is to improve the quality of life by relieving pain with the use of oral opioids.
What the health worker should do Health education The Core Cancer Health Education Module recommended for the Region (see Chapter 6 - Health education) includes promoting cancer awareness of the fact that the great majority of liver cancer in the Region is caused by Hepatitis B Virus, and persuading mothers to have infants and young children undergo HBV vaccination.
Palliative care As the majority of liver cancers are advanced at the time of diagnosis, health workers ought to be able to participate in the relief of pain and other symptoms, and to assist in social, psychological and spiritual support.
-223-
Manual on the prevention and control of common cancers
References and suggested readings 1. 2. Eddy DM. Secondary prevention of cancer: an overview. Bulletin of the World Health Organization, l986, 64(3): 421-429. Fleming ID, Cooper JS, Henson DE, Hutter RVP, Kennedy BJ, Murphy GP, O’Sullivan B, Sabin LH, Yarbro JW (editors ) AJCC Cancer Staging Manual. Fifth edition. American Joint Committee on Cancer; Lippincott-Raven, 1997. National control programmes: policies and managerial guidelines. Geneva, World Health Organization, l995. Pisani P, Parkin DM, Muñoz N. Ferlay J. Cancer and infections: estimates of the attributable fraction in l990. (submitted for publication). Prevention of liver cancer. Geneva, World Health Organization, l983 (WHO Technical Report, Series 69l). Shiu W, Tang ZY. Liver Cancer. In: Love RR (editor) Manual of clinical oncology. Sixth Edition. International Union Against Cancer; SpringerVerlag l994: 303-309. Tomatis L. (editor) Cancer: causes, occurrence and control. Lyon, International Agency for Research on Cancer, l990 (IARC Scientific Publications No. l00). Van Parijs L.G. Public education in cancer prevention. Bulletin of the World Health Organization, l986, 64(6): 917-927. World Progress in Surgery. Benign and Malignant Tumors of the Liver. World Journal of Surgery, 1995, 19(1).
3. 4. 5. 6.
7. 8. 9.
-224-
14. Lung cancer Magnitude, cause and prevention Magnitude
L
ung cancer is currently the most common cancer worldwide and the number of new cases is increasing at a rate of about 0.5 per cent per year. In l980, there were an estimated 660 500 new cases, which comprised 10.4 per cent of all cancers. The incidence rates varied among countries. This international variation was explained by different levels of exposure to the main cause of lung cancer - cigarette smoking. Higher incidence rates for males, compared with females, and among urban, compared with rural populations, are also explained by higher prevalences of cigarette smoking. Rates among females have been increasing rapidly as more women begin smoking. Lung cancer was relatively rare at the beginning of this century, and trends in incidence rates among age and gender groups in different countries can be explained almost completely by national tobacco smoking habits. These trends reflect the prevalence of smoking among different generations and the tar contents of the cigarettes smoked. Table 14.1 shows the 1990 estimated age-standardized rates (ASR) of lung cancer incidence in ten countries and one area in the Western Pacific Region.
Manual on the prevention and control of common cancers
Table 14.1. Lung Cancer: age-standardized incidence rates (ASR) per l00 000 in ten countries and one area in the Western Pacific Region (l990 Estimates, Reference 10). COUNTRY/AREA ASR Australia China Hong Kong Japan Malaysia New Zealand Papua New Guinea Philippines Republic of Korea Singapore Viet Nam 48.01 48.83 77.50 37.52 45.80 51.46 5.40 37.26 24.35 56.81 62.25 MALES %ALL CANCERS 17.16 19.44 24.23 14.09 25.52 17.23 2.89 24.46 11.49 25.19 25.06 ASR 14.45 20.01 32.90 10.78 15.20 19.89 2.76 10.58 6.18 19.00 14.31 FEMALES % ALL CANCERS 6.03 9.75 15.04 6.29 10.53 6.96 1.48 7.44 4.16 9.61 7.51
Among males, the highest lung cancer rates were estimated for Hong Kong, closely followed by Viet Nam, Singapore, New Zealand, China, Australia and Malaysia. The lowest estimated rates were for Papua New Guinea (PNG). In the middle were Japan and the Philippines, where estimated rates were similar and slightly less than half of those estimated for Vietnamese males. Among females, the highest rates estimated were in Hong Kong, Malaysia, China, New Zealand and Singapore. Again, the lowest was among PNG women, while estimated rates among Vietnamese, Japanese and Filipino females were similar.
Cause Cigarette smoking causes lung cancer, a fact that was recognized in the UK and the USA in the early l950s and has been indubitably reinforced by subsequent and continuing evidence.
-226-
Lung cancer
Numerous investigations, conducted in different countries on different population subsets and using different study designs, have consistently reported a greater increase in the occurrence of lung cancer among smokers compared with non-smokers. Major studies have shown a clear dose-response relationship between the amount smoked daily and the subsequent risk of lung cancer (Table 14.2). The risk has been assessed as about 20 times higher for smokers of one pack a day for 30 years or more, than for non-smokers. Table 14.2. Risks for male cigarette smokers of dying from lung cancer, relative to nonsmokers, in some major cohort studies. (Reference 11). Country No. of subjects in study Daily no. of cigarette s 0 1-9 10-14 15-24 25-49 > 50 Sweden 27 342 0 1-7 8-15 15-24 > 25 UK 34 440 0 1-14 15-24 > 25 USA 440 558 0 1-9 10-19 20-39 > 40 a
Relative risk a
Reference
Japan
122 261
1.0 1.9 3.5 4.1 4.6 5.7 l.0 2.1 7.8 12.7 25.1 1.0 7.8 12.7 25.1 l.0 4.6 7.5 13.1 16.1
Hirayama (l974)
Cederlof et al. (1975)
Doll & Peto (1976)
Hammond (l996)
Ratio between the occurrence rate of cancer among smokers and that among nonsmokers
The association with cigarette smoking is present for all histologic types of lung cancer but is strongest for squamous cell carcinomas, the type that has increased dramatically. Cigarette smoking induces lung
-227-
Manual on the prevention and control of common cancers
cancer in experimental animals, and cigarettes contain chemicals which are known to produce cancer in animals and humans. It has also been established that sidestream smoke, the smoke emitted into the air, contains higher concentrations of some carcinogenic substances than mainstream smoke, the smoke inhaled by smokers. Many epidemioligical investigations, including three cohort studies, have demonstrated a relative increase of 20-50 per cent in the risk of lung cancer for non-smoking spouses of smokers.
Prevention Since at present there is no effective method of secondary prevention (early detection) of this rapidly progressive and highly fatal affliction, the best approach is through primary prevention. The prevalence of cigarette smoking must be substantially decreased by: 1) preventing non-smokers from taking up the habit and becoming addicted to nicotine; 2) persuading and supporting smokers to give it up; and 3) encouraging smokers to reduce their consumption, although this is the least effective in reducing both the personal risk as well as the national risk of contracting lung cancer. Successful tobacco-control programmes have demonstrated clear success in lowering lung cancer rates. Population time-trend studies have confirmed declines in Finland, the UK and the USA which were explained by changes in smoking habits. Table 14.3. Relative risk for developing lung cancer by time since stopping smoking and total duration of smoking habit (Reference 11).a Time since stopping smoking years Duration of smoking habit (years) 1-19 Men 0 1-4 5-9 > 10 Women 0 1-4 5-9 > 10 a
20-39
40-49
>50
1.0b 1.1 0.4 0.3 1.0c 1.0 0.4 0.4
2.2 2.1 1.5 l.0 2.1 2.3 2.0 0.8
2.8 3.3 2.2 l.6 2.7 2.1 1.1 2.3
3.0 3.8 2.8 2.7 5.2 7.1 1.7
From Lubin et al. (l984a)
-228-
Lung cancer b
Baseline category: risk for men who had never smoked relative to that for current smokers who had smoked for one to l9 years was 0.3. c Baseline category: risk for women who had never relative to that for current smokers who had smoked for one to l9 years was 0.6.
Epidemiological studies of ex-smokers have consistently shown lower risks of lung cancer compared with current smokers (Table 14.3), the risk progressively declining with the increase in the number of years since smoking stopped. However, the risk of lung cancer for ex-smokers does not decline to the same low level as for those who have never smoked, so that preventing individuals from ever smoking is still the best primary prevention strategy.
The lung cancer control programme Primary prevention Control of lung cancer should concentrate on primary prevention, specifically tobacco-control activities. The general objective is to reduce the incidence of lung cancer caused by tobacco. More specific objectives might include the following: • • • to reduce the number of young people starting smoking; to increase the number of people giving up smoking; to educate all schoolchildren about the effects of tobacco on health; to inform everyone in the population, smokers and non-smokers, of the risks associated with smoking; to inform smokers about the benefits of giving up smoking and the steps they can take to do so; to provide support to people who want to stop smoking; -229-
•
•
•
Manual on the prevention and control of common cancers
•
to create a smoke-free environment to minimize the effects of passive smoking.
-230-
Lung cancer
The process should include: • • establishing education programmes, especially for school children; establishing a clear policy on legislative measures, particularly price increases and taxation on cigarettes; establishing a national, multidisciplinary tobacco-control committee, with members drawn not only from all concerned government ministries but also from nongovernmental organizations that can advise on strategies appropriate to national culture.
•
The following measures should be taken to assess the outcome of the control programme: • In the short term, a prevalence study of smoking/chewing tobacco should be undertaken to determine the proportion of adolescents and adults who are regular smokers or chewers of tobacco. From the results of such a survey, or from other data, the following may be determined: - the percentage of school curricula and adult literacy programmes that include information on tobacco; - the percentage of health-professional education programmes and continuing-education programmes that include information on tobacco. • In the medium term, assessment should be made of the changes in the incidence of tobacco-associated conditions other than cancer, such as coronary heart disease, and cardiovascular and respiratory diseases. In the long term, an assessment of the reduction in mortality due to lung cancer and other tobacco-linked cancers, and in chronic obstructive lung disease, should be made.
•
-231-
Manual on the prevention and control of common cancers
The main features of the tobacco control programme are summarized diagrammatically in Figure 14. Figure 14: Primary prevention - Tobacco
Implementation Establish a national anti-tobacco council Appont an administrator of the programme with appropriate support (e.g. NCCP coordinator) Perform a sampling survey to determine prevalence of tobacco use Set up a threeforl strategy based on the following:
Education Especially of schoolchildren from age 10 years Promote peer-to-peer programmes for adolescents Mass education Integrate with related messages (e.g. heart and lung disease) Use the influence of the media
Legislation Taxation Regular price increases Ban on advertising Warning labels Ban smoking in public places Ban toabcco sales to minors End subsidies to tobacco industry Encourage alternative crops in tobacco-growing areas Regulate tobacco exports
National leadership Promote domestic cooperation and advocacy by both government and NGOs Collaborate internationally on non-smoking policies and reduction in tobacco trade
Process measures >80% schoolchildren aged 10 years and over receive education about smoking >50% of adults receive an anti-smoking message each year >4 out of 9 legislative measures to control tobacco are implemented Impact measures >80% of schoolchildren aged 10 years and over aware of hazards of smoking >50% of adults aware that smoking causes lung cancer >30% of adult smokers intend to quit within one year Outcome measures <30% of adolescents are regular smokers <50% of adult males and <30% of adult females smoke Medium term: reduction in incidence of diseases (e.g. cardiovascular, respiratory) Long term: reduction in mortality from diseases (lung cancer, etc.) Short term:
Source: National Cancer Control Programmes, Geneva, WHO, 1997
-232-
Lung cancer
Secondary prevention - early detection
Screening Screening for lung cancer has been attempted using radiologic and cytological methods. Unfortunately, studies have failed to establish the effectiveness of such screening techniques in decreasing mortality. This failure may be attributed to the aggressiveness of small lesions and their propensity to early distant metastasis.
Early diagnosis and curative treatment The concept of detecting lung cancer early among symptomatic patients is usually futile since appearance of symptoms occurs late in the course of the disease. Due to the absence of pain fibres in the lung parenchyma, symptoms usually occur with advanced disease. Other symptoms are dependent on the size, location and degree of involvement of tissues at the primary or metastatic site. Centrally-located endobronchial tumours may manifest as a cough (70 per cent of cases), dyspnoea, haemoptysis, recurrent lower respiratory infections and dull pain on the chest. In contrast, peripheral tumours may exhibit stabbing pain, pleural effusion with dyspnoea or hoarseness due to vocal cord paralysis from recurrent nerve involvement in the mediastinum. Nonetheless, patients with a chronic cough or any other of the abovementioned symptoms should at least undergo a chest X -ray and sputum cytology to detect cancer, and it should then be determined if the patient could benefit from curative treatment. At present, only 10 per cent of all lung cancer patients may benefit from treatment at the time of diagnosis. In the United States in 1960, the overall five-year survival rate ranged between 5 -10 per cent, and had increased only modestly to 14 per cent by 1993. The most significant advance has been in the proper selection of patients for curative resection through meticulous preoperative staging procedures. Diagnosis and staging aims to determine the histologic nature of the disease and the possibility and extent of surgical resection. The signs and symptoms and a thorough physical examination are the most efficient guides to a systematic evaluation.
-233-
Manual on the prevention and control of common cancers
The chest X-ray is usually the first test that suggests lung cancer. As the majority are advanced on presentation, the chest X -ray will in many cases indicate that resection is no longer indicated. The next step is to determine histology, specifically whether small-cell carcinomas or nonsmall-cell carcinomas are present. Sputum cytology can diagnose approximately 50 per cent of all bronchogenic cancers, particularly with good (induced or transtracheal) sputum collection in patients with centrally located lesions. Bronchoscopy and biopsy is a very useful diagnostic procedure for centrally-located tumours seen on X -ray. It may also provide information on resectability by assessing the proximity of the tumour to the carina. Percutaneous needle lung biopsy (PNLB) provides a histologic diagnosis for peripherally located tumours. Tissue may be taken from the tumour, pleura or chest wall. In addition, pleural fluid may be cytologically assessed for malignant cells. Fine needle aspiration biopsy (FNAB) may be an alternative. Computerized axial tomography (CT) increases sampling accuracy. CT scanning is a valuable tool for determining tumour location and lymph node involvement. Coupled with percutaneous biopsy, it may provide the most accurate information regarding histology and curability/resectability, short of an open procedure like a mediastinoscopy. CT scanning of the upper abdomen may be used to determine possible liver metastasis. Mediastinoscopy and mediastinotomy are procedures used to assess mediastinal lymph node involvement. Contralateral nodes or extensive extranodular cancer is a contraindication to surgical resection. Some believe that in stage III-A disease (with positive mediastinal nodes) surgical treatment is of no further value. It is very important to emphasize that curative treatment for lung cancer is to be considered only when adequate resources are available. Within the context of a national cancer control programme, active treatment of lung cancer has a lower priority than treatment of more curable cancers. Active treatment of lung cancer should be attempted only in institutions where multidisciplinary specialists and sophisticated facilities are present, bearing in mind that, even with the most expensive technology available, lung cancer is rarely cured.
Non-small-cell lung cancer (NSCLC)
-234-
Lung cancer
TNM Staging for NSCLC is shown in Appendix 3. Surgical resection is the treatment of choice for physically fit patients with NSCLC limited to the lung parenchyma (Stage I), or with ipsilateral bronchopulmonary lymph node spread (Stage II). The five-year survival rate is 40 per cent, indicating that, in spite of a vigorous preoperative search for metastasis, the majority still die from distant spread within five years. The benefits of surgery for patients with Stage IIIA disease is still unclear. Major contraindications to surgery include: 1) stages III-B or IV disease; 2) hoarseness with vocal cord paralysis; 3) superior vena caval syndrome; 4) inadequate pulmonary function; 5) severe cardiac disease myocardial infarction). (heart failure, arrhythmia, recent
Symptoms of patients who are not fit for surgical resection may be relieved by radiotherapy but survival is not improved. Radiation therapy and chemotherapy have not yet contributed to any significant improvement in cure rates - whether used alone, combined with one another, or adjuvant to surgical resection.
Small-cell lung cancer (SCLC) SCLC is divided into "limited" and "extensive" stage categories. "Limited" means that the tumour is limited to one hemithorax including ipsilateral lymph nodes up to the N3 level, supraclavicular nodes, and a pleural effusion. Any spread beyond this is categorized as "extensive" disease. Patients with both limited and extensive stages of SCLC are considered candidates for chemotherapy. If left untreated, death is expected within a few weeks and systemic chemotherapy unquestionably improves survival, with a marked reduction in symptoms and tumour regression in over 50 per cent of patients. Unfortunately, the duration of the remission is only six to ten months because of primary drug resistance. Combination chemotherapy is superior to monotherapy, with schedules containing platinum derivatives giving the best response. Complete remission of 40-50 per cent is achieved when the disease is limited, and only 20-30 per cent in -235-
Manual on the prevention and control of common cancers
extensive disease. The overall remission rate is 90-95 per cent for patients with limited disease and 60-80 per cent for those with extensive disease. Radiotherapy is limited to decreasing local recurrence and brain metastasis when given prophylactically in these areas. Brain metastasis occurs in 50 per cent of patients without irradiation and is reduced to 15 per cent after brain radiotherapy.
Palliative treatment Even in developed countries, 90 per cent of patients with lung cancer die of the disease. Symptoms referable to the thorax, such as chest pain and shortness of breath are the predominant sources of suffering. Pain control, particularly with morphine sulfate, is the mainstay of palliative treatment, together with radiation to bone, brain and spinal cord. Chemotherapy should be limited to SCLC which shows a significant response and improvement in symptoms. Dyspnoea secondary to effusion is relieved by repeated thoracentesis or thoracostomy. Pleurodesis utilizing agents that provoke a severe pleural inflammation such as talc or tetracycline, which heals by fibrosis and obliterates the pleural space, may prevent or minimize recurrent pleural effusion.
What the health worker should do Health education The Core Cancer Health Education Module recommended for the Region (see Chapter 6 - Health education) includes 1) promoting cancer awareness of the WHO Tobacco or Health programme, and promoting a healthy diet, and 2) persuading and supporting smokers to stop smoking. Tobacco control and a healthy diet are the two most important primary prevention measures for many noncommunicable diseases including many types of cancer and especially lung cancer.
-236-
Lung cancer
Early detection When facilities for diagnosis, staging and treatment are present, the health worker should be on the lookout for adults, particularly those with a long history of cigarette smoking, who complain of dyspnoea, hemoptysis, recurrent pneumonia, chest pain and hoarseness. Particularly in developing countries, health workers must be able to accurately and rapidly distinguish probable lung cancer cases from those with pulmonary tuberculosis, and refer accordingly.
Palliative care When active intervention measures (e.g., surgery, radiotherapy, chemotherapy) are not feasible or available, as they quite frequently are in a large majority of cases, pain and symptom control, with social, psychological and spiritual support should be given in order to improve the quality of remaining life.
-237-
Manual on the prevention and control of common cancers
References and suggested readings 1. 2. 3. 5. Action Plan on Tobacco or Health for l995-l999. Manila, World H ealth Organization Regional Office for the Western Pacific, l995. Ball K. Smoking spells death for millions. World Health Forum, l986, 7: 211-2l6. Chandler WU. Tobacco-strong words are not enough. World Health Forum, l986, 7:217-223. Fleming ID, Cooper JS, Henson DE, Hutter RVP, Kennedy BJ, Murphy GP, O’ Sullivan B, Sabin LH, Yarbro JW (editors) AJCC Cancer Staging Manual. Fifth Edition. American Joint Committee on Cancer; Lippincott-Raven, 1997. Eddy DM. Secondary prevention of cancer: an overview. Bulletin of the World Health Organization, l986, 64(3): 421-429. Gatzemeier DK, Hossfeld DK, Love RR. Lung Cancer. In: Love RR (ed.) Manual of clinical oncology. Sixth edition. International Union Against Cancer; Springer-Verlag, l994: 288-302. Havas S. Prevention of heart disease, cancer and stroke: the scientific basis. World Health Forum, l987, 8:344-351. Havas S. Prevention of heart disease, cancer and stroke: the Massachusetts approach. World Health Forum, l987, 8:352-356. National cancer control programmes: policies and managerial guidelines. Geneva, World Health Organization, l995.
4. 6.
7. 8. 9.
10. Pisani P, Parkin DM, Muñoz N, Ferlay J. Cancer and infection: estimates of the attributable fraction in l990 (submitted for publication). 11. Roemer R, Adrianza M, El Bedly H, Daube MM, de Givry U, Mackay J, Omar S, Ramstrom LM. Legislation to control smoking: a round table. International Digest of Health Legislation, l986, 37(3): 447-474. 12. Roemer R. Legislative action to combat the world tobacco epidemic. Geneva, World Health Organization, l993. 13. Smoking control strategies in developing countries, Geneva, World Health Organization, l983 (WHO Technical Report Series 695).
-238-
Lung cancer
14. Tobacco Smoking. Lyon, International Agency for Research on Cancer, l986, (IARC Monographs on the Evaluation of Carcinogenic Risks to Humans Vol. 38). 15. Tomatis (editor) Cancer: causes, occurrence and control. Lyon, International Agency for Research on Cancer, l990 (IARC Scientific Publications No. l00). 16. Van Parijs LG. Public education in cancer prevention. Bulletin of the World Health Organization, l986, 64(6): 917-927. 17. World progress in surgery - staging and management of lung cancer. World Journal of Surgery, l983, 17(6).
-239-
15.
Skin cancer
Magnitude, cause and prevention Magnitude
I
n general, there is a lack of accurate incidence data on skin cancers other than melanomas (i.e. squamous cell carcinomas and basal cell carcinomas) as many cases are not registered. Patients with these cancers are usually treated as outpatients and many excised specimens are not submitted for histological diagnosis. As many skin cancers are cured by excision, cautery and other destructive methods, the necessity of histological diagnosis is not seen as important by the treating physicians and the real magnitude of the problem cannot be ascertained. For most populations, skin cancer risk is inversely related to the individual's skin colour, and directly related to exposure to sunlight. In the USA, the incidence of skin cancer is about l00 times higher for the Caucasian population than for the African American. Within Australia and the USA, residents of areas nearer the equator have a two to threefold higher incidence rate for skin cancer than those residing within latitudes farthest from the equator. Males have about twice as many non-melanoma skin cancers as females, and the anatomical distribution of skin cancers reflects the typical clothing patterns of each sex. A large US survey suggested that a 1 per cent increase in ultraviolet (UV) radiation would cause a 1-2 per cent increase in the incidence of skin cancer. The continuing depletion of stratospheric ozone, which is the main shield against UV radiation, will likely lead to an increasing incidence of skin cancer.
Manual on the prevention and control of common cancers
The registration of melanomas is more accurate. This may be partly because they are much less curable than non-pigmented skin cancers and are usually treated in hospital. Table 15 shows the 1990 estimated age-standardized incidence rates (ASR) for melonoma in ten countries and one area in the Western Pacific Region. Table 15. Melanoma: age-standardized incidence rates (ASR) per l00 000 in ten countries and one area in the Western Pacific Region (1990 Estimates, Reference 5). COUNTRY/AREA ASR MALES % ALL CANCERS 8.30 0.22 0.25 0.l8 0.22 8.67 3.94 0.31 0.ll 0.36 0.25 ASR FEMALES % ALL CANCERS 8.99 0.29 0.46 0.17 0.28 5.05 2.50 0.14 0.14 0.14 0.32
Australia China Hong Kong Japan Malaysia New Zealand Papua New Guinea Philippines Republic of Korea Singapore Viet Nam
23.23 0.54 0.80 0.48 0.40 25.90 7.35 0.47 0.23 0.81 0.62
21.56 0.60 1.00 0.29 0.40 23.60 4.66 0.20 0.21 0.27 0.60
The estimated incidence of melanoma in Australia and New Zealand was more than twenty times higher than in the other countries, with the exception of Papua New Guinea. Rates in these two countries were similar for males and females. In the low-risk countries, rates for both sexes were less than 1 per l00 000. Basal cell carcinomas, with a very high incidence rate in Australia and New Zealand, also occur among Asians, mostly on the face. Squamous cell -240-
Skin cancer
carcinomas, more related to UV radiation exposure, have a very high incidence rate in New Zealand and are rare elsewhere in the Region, except on the legs of Melanesians with chronic tropical ulcers. Rates for melanomas are very high in Australia and New Zealand. They are very low elsewhere, with occurrence mainly on the feet.
Cause Epidemiological data demonstrate a causal relationship between exposure to sunlight and cancers of the skin. It is the ultraviolet (UV) frequency range that is presumed to be the carcinogenic component of sunlight because of its known tissue-damaging and mutagenic effects. UV radiation produces skin tumours in experimental animals. Skin pigmentation may be an important determinant of risk because it determines the amount of sun exposure at the level of the target cells. The incidence among similarly fair-skinned populations increases as the place of residence gets nearer the equator, but this is not so among darkerskinned populations. Exposure to UV radiation is related to all forms of skin cancer, but the epidemiological evidence is more straightforward for non-melanoma skin cancers. There is now evidence that intermittent exposure is more harmful than continuous exposure, at least for melanomas at some sites. Individuals who are able to maintain suntans have a lower risk compared to periodic "sunburners". Exposure in children and early adolescence may confer a greater risk than exposure in adult life.
Prevention The most obvious primary prevention measure is sun avoidance and the use of hats and umbrellas during recreational and occupational activities in the middle four hours of the day. Fair-skinned Caucasians who live at low latitudes, such as in Australia, New Zealand and Papua New Guinea are at greatest risk. National lifestyles and habits are difficult to change, and it will be interesting to discover the long-term results of sun avoidance programmes, such as in Australia. Secondary prevention can be accomplished by educating the population, particularly those at high risk, on the signs of skin cancer and the need to consult early when suspicious lesions are discovered. -241-
Manual on the prevention and control of common cancers
The skin cancer control programme Primary prevention Skin cancer incidence can be reduced by primary prevention, specifically by avoiding excessive ultraviolet radiation from the sun, particularly among susceptible persons. The key measures which should be undertaken are the following: • Increase the number of people who are aware of their own risk factors for skin cancer. Persuade people at high risk to avoid exposure to the sun and artificial sources of ultraviolet radiation, and to adopt appropriate avoidance behaviour and sun-protection measures for themselves and their children. This will involve using hats, umbrellas and appropriate clothing. Where sun exposure is unavoidable, broadspectrum sunscreen with high SPFs should be used. Effect changes in public attitudes to a tanned appearance.
•
•
The main features of a programme to reduce excessive exposure to sunlight are summarized diagrammatically in Figure 15.1.
Secondary prevention - early detection Screening and early diagnosis Screening and early diagnosis of skin cancer go hand in hand. Secondary prevention (early detection), targeted at susceptible populations should consist of educating the public and health workers on the suspicious features of pigmented and non-pigmented skin lesions, and training health workers on the proper biopsy technique for suspicious non-pigmented lesions.
-242-
Skin cancer
Figure 15.1: Primary prevention - overexposure to sunlight
Implementation Collaborate with those at government and NGO level interested in control of excessive sun exposure Perform a sampling survey to identify current beliefs on dangers of sun exposure Set up a threefold strategy based on the following:
Education Mass education School education Target health professionals Link with other elements of a healthy lifestyle (e.g. exercise) Target high-risk groups (e.g. outdoor occupations, certain recreational activities) Use the influence of the media
Legislation Regulate agents that deplete the ozone layer (e.g. chlorofluorocarbons) Require employers to provide protection for workers at risk Regulate solariums (tanning parlours) Promote standards for protective devices (e.g. sun filters, sunscreens)
National leadership Promote interdisciplinary and interministerial collaboration Promote domestic and international collaboration with governments and NGOs
Process measures >80% of schoolchildren aged 10 years and over receive education on hazards of sun exposure >50% of adults see educational message about hazards of sun exposure each year Impact measures >80% of schoolchildren aged 10 years and over aware of hazards of sun exposure >50% of adults aware of link between cancer and sun exposure Adopt regulations to ban use of chemicals that damage the ozone layer Outcome measures >50% of adults actively moderating their sun exposure monitor thickness of ozone layer and ultraviolet radiation level Medium term: reduction in prevalence of sun-damaged skin Long term: reduction in incidence of skin cancers Short term:
Source: National cancer control programmes, Geneva, WHO, 1995.
-243-
Manual on the prevention and control of common cancers
A health worker should be able to suspect skin cancer by its history and appearance. Early detection is achieved by adequate physical inspection by the health worker on a regular basis, particularly for those who are at high risk. These are persons who expose themselves to the sun by nature of work or habit. Caucasians are more predisposed to suninduced changes leading to skin cancer because of the deficiency of melanin pigment. Health education should aim to prevent lesions as well as to detect them earlier, since these can be easily observed by the patients and their companions. The warning signs of skin cancer should be disseminated to the community in order to increase awareness and diagnose cases early. The most common histological types of skin cancer are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). BCC is four times more common than SCC. Suspicious early lesions are the following: • Persistent ulcers that heal intermittently or exhibit minimal bleeding. Bleeding, ulceration, or asymmetric nodularity in a patient with actinic (solar) keratosis. Ulceration or nodularity in previously irradiated skin, scar or sinus tract. Chronic reddish patches with erosions which are not healing.
•
•
•
While melanomas comprise only a small proportion of skin cancers, it is important to diagnose them even earlier in order to prevent distant metastases which are very hard to treat and cause death in a large proportion of patients. Melanomas may be distinguished from melanocytic nevi and other benign pigmented lesions on the basis of ABCDE. Melanomas may have:
Asymmetric shape. Border irregularity. Colour variation within the lesion including brown, black, blue, red and white hives. Colour of lesion darkening or blackening
Diameter of lesion Enlarging.
-244-
Skin cancer
A brown lesion which has any two of the first three signs, or either diameter enlarging or colour darkening alone should be regarded as highly suspicious of melanoma.
Curative treatment Non-pigmented skin cancers (BCC and SCC) seldom spread to distant organs, and the majority are curable either by surgery or radiotherapy. Small lesions can be excised by health workers. Bigger lesions, particularly those in the face, will have to be referred to specialists. Pigmented skin cancers (melanomas) are divided into 3 stages at diagnosis. Stage I. Stage II. Stage III. melanoma confined to the skin involvement of regional lymph nodes distant metastases
The most important prognostic variable is the thickness of the lesion. Thin melanomas (<1 mm) are curable and no further work-up is needed. For thicker lesions a full examination of lymph nodes is required to look for distant metastases. Other tests are used only when indicated. Suspicious pigmented skin lesions should be referred for appropriate treatment.
Palliative treatment Unfortunately many cases of melanoma are still not diagnosed early. The prognosis for patients with stages II and III of the disease is very poor. There is no efficient active systemic treatment for metastases that consistently results in relief of symptoms or increased survival. Melanomas commonly spread to regional lymph nodes, liver, lungs and brain. Relief of pain and other symptoms, and psychosocial and spiritual support should be given.
What the health worker should do -245-
Manual on the prevention and control of common cancers
Health education In certain countries of the Region, notably Australia and New Zealand, the incidence of skin cancer is high enough to warrant strong public health measures. The public should be made completely aware of the importance of avoiding excessive exposure to sunlight, especially in the middle part of the day, and in particular of avoiding sunburn. The use of sunscreen to avoid sunburn and using hats and umbrellas should be constantly encouraged, particularly among light-skinned persons who do not tan, and sunburn easily.
Early detection The health worker should be familiar with the warning signs for pigmented and non-pigmented skin lesions. The public should be made aware of these signs and periodically examine their skin.
The warning signs for pigmented skin lesions are (ABCDE):
Assymetric shape. Border irregularity. Colour variation within the lesion, including brown, black, blue, red and white hues, or colour or lesion darkening or blackening.
Diameter Enlarging. The warning signs for non-pigmented skin lesions are: •
Persistent ulcers that heal intermittently or exhibit minimal bleeding.
-246-
Skin cancer
•
Bleeding, ulceration, asymmetric nodularity in an actinic (solar) keratosis. (Figure 15.2)
(please see attached slide)
•
Ulceration or nodularity in previously irradiated skin, scar or sinus tract. Chronic reddish patches with erosions which are not healing.
•
A strong light and a hand held magnifying lens are required for proper inspection of skin lesions. The health worker should be able to do an excision biopsy of small nonpigmented lesions. For large lesions, a section biopsy is done, and the patient referred accordingly.
The steps in an excision biopsy are as follows: 1. The skin is prepared with an antiseptic (povidone iodine, chlorhexidene, hexachlorophene). A local anaesthetic agent is infiltrated into the planned incision site. If lidocaine is used, the maximum safe dose is 7.5 mg/kg. For large areas, it is preferable to use a diluted solution.
2.
-247-
Manual on the prevention and control of common cancers
3.
A l.0 cm lateral (Figure 15.3A) and inferior (Figures 15.3B and 15.3C) margin from the tumour is usually sufficient. The skin is closed with interrupted sutures (Figure 15.3D). Post-operatively, two or three doses of a non-steroidal antiinflammatory drug (NSAID) are sufficient to control postoperative pain. No antibiotics are needed.
4. 5.
Health workers should not attempt to biopsy suspicious pigmented lesions and should refer them to hospital for management. Figure 15.3: Excision biopsy. Adequate margins both on the surface and in depth are required.
Source: Primary care surgery for family physicians. Manila, Philippine College of Surgeons, 1993 (PCS Scientific Publications No. 8).
-248-
Skin cancer
Palliative care When active intervention measures (e.g. surgery, radiotherapy) are not feasible or available, pain and symptom control, with social, psychological and spiritual support should be given in order to improve the quality of remaining life.
-249-
Manual on the prevention and control of common cancers
References and suggested readings 1. 2. Eddy DM. Secondary prevention of cancer: an overview. Bulletin of the World Health Organization, l986, 64(3): 421-429. Friedman R. Sherman CD Jr. Skin cancer. In: Love RR (editor) Manual of clinical oncology. Sixth Edition; International Union Against Cancer: Springer-Verlag: 235-243. Marks R, Gill PG. Melanoma of the skin. In Love RR (editor) Manual of clinical oncology. Sixth Edition; International Union Against Cancer; Springer-Verlag: 244-258. National cancer control programmes: policies and managerial guidelines. Geneva, World Health Organization, l995. Pisani P. Parkin DM, Muñoz N, Ferlay J. Cancer and infection: estimates of the attributable fraction in l990 (submitted for publication.) Some naturally occurring and synthetic food components, furocoumarins and ultraviolet radiation. Lyon, International Agency for Research on Cancer, l986 (IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 40). Tomatis L (editor) Cancer: causes, occurrence and control. Lyon, International Agency for Research on Cancer, l990 (IARC. Scientific Publications No. l00).
3.
4. 5. 6.
7.
-250-
Skin cancer
Source: National cancer control programmes, Geneva, WHO, 1995.
Source: National cancer control programmes, Geneva, WHO, 1995.
Source: National cancer control programmes, Geneva, WHO, 1995.
Source: National cancer control programmes, Geneva, WHO, 1995.
Source: National cancer control programmes, Geneva, WHO, 1995.
Source: National cancer control programmes, Geneva, WHO, 1995.
Source: National cancer control programmes, Geneva, WHO, 1995.
Source: National cancer control programmes, Geneva, WHO, 1995.
Source: National cancer control programmes, Geneva, WHO, 1995.
Source: National cancer control programmes, Geneva, WHO, 1995.
-251-
16.
Breast cancer
Magnitude, cause and prevention Magnitude
B
reast cancer is the third most common cancer worldwide and is the most common cancer in women. In 1980 it comprised nine per cent of the global cancer burden, even although occurring almost exclusively among women. It ranks third in developed countries, and fifth in developing countries. Incidence rates are high in most industrialized countries (except Japan), and low in central and tropical South America, Africa and Asia. The incidence curve for breast cancer rises with age from 30 to 70 years. There is considerable variation within countries according to sociodemographic factors such as race, social class, marital status and region of residence. Table 16 shows the 1990 estimated age-standardized rates (ASR) per 100 000 in ten countries and one area in the Western Pacific Region. The highest estimated incidence rates were in New Zealand and Australia where breast cancer comprised a quarter of all female cancers, while the lowest rate was in the Republic of Korea. Intermediate rates were estimated for the other eight countries. Increasing trends in incidence have been observed in many countries, and, together with the observed changes in risk in migrant populations, may be related to changes in reproductive and dietary behaviours.
Manual on the prevention and control of common cancers
Table 16. Breast Cancer, Female: age-standardized incidence rates (ASR) per 100,000 in ten countries and one area in the Western Pacific Region (1990 Estimates, Reference 8). COUNTRY/AREA ASR %ALL CANCERS IN FEMALES 25.52 9.96 14.17 15.34 18.63 26.01 12.19 23.00 8.55 19.35 17.43
Australia China Hong Kong Japan Malaysia New Zealand Papua New Guinea Philippines Republic of Korea Singapore Viet Nam
61.21 20.45 31.00 26.26 26.90 74.33 22.65 32.72 12.70 38.26 33.20
Cause The fact that breast cancer almost exclusively occurs in females strongly indicates that reproductive and hormonal factors are involved. Whatever the overall incidence rates, the basic shape of the incidence curve by birth cohort is similar in all populations, emphasizing the effect of ovarian activity on the susceptibility of breast epithelium to neoplastic transformation. Commonly recognized factors that confer a higher risk are early menarche, late menopause and first full-term pregnancy at age 30 years and older. Obesity in post-menopausal women has been incriminated, and the associated increase in risk has been partly explained by the fact that adipose tissue is the main source of oestrogens in postmenopausal women. Some studies have reported a protective effect from delayed menarche, early menopause (natural or induced) first full-term pregnancy occurring at age 20 and high parity.
-252-
Increasing incidence in some countries that have progressed from developing to developed status has been attributed to changing reproductive behaviour, such as smaller family size and higher age at first full-term pregnancy. A change in diet is probably also responsible for the increasing incidence seen in countries which have undergone an epidemiological transition, such as Singapore. While there is no conclusive evidence that a high fat diet may be a causal factor in breast cancer, the promotion of a healthy diet is considered to be sensible from a public health perspective. Exercise and the consumption of fruits and vegetables are important protective factors and the degree of protection is highest when started at an early age (i.e. childhood and adolescence). Scientists continue to carry out further investigations on issues such as the relative importance of total fat and saturated fat, and the accuracy and reliability of different dietary assessment methods.
Prevention Breast cancer is one of only a few cancers (i.e. cancers of the cervix, breast and mouth) for which a good opportunity for both primary and secondary prevention currently exists by methods which are practical enough to be implemented regionally. In primary prevention, reproductive modification is not a practical measure as it may be extremely difficult from a social, cultural and economic sense to convince women to have more babies, and earlier, in order to prevent breast cancer. On the contrary, as nations progress economically the tendency is to adopt child-bearing patterns that increase the risk of breast cancer, making the other primary prevention option, dietary modification, even more important. Nevertheless, such information on both promotive and protective reproductive behaviour should be made available to women. While fat is the dietary component implicated in breast cancer risk, the public health programme should not involve only fat, or its association with breast cancer and other cancers, but rather promote the notion that the "affluent" diet is bad for health, and that a healthy diet is beneficial. The "affluent" diet, high in fat, salt and free sugars and low in whole grains, vegetables and fruits, increases the risk of cancer, cardiovascular diseases and many other chronic diseases, and may also lead to deficiency states. A healthy diet, low in fat, salt and free sugars and high in whole grains, tubers, lentils, vegetables and fruits, decreases the occurrence of both deficiency states and many chronic diseases, including cancer.
-253-
Manual on the prevention and control of common cancers
For secondary prevention (early detection) the use of mammographic screening has repeatedly demonstrated a mortality benefit compared with unscreened populations. The reduced mortality has, however, only been consistently demonstrated for women of 50 years and older. However, the resources needed to undertake a full-scale mammographic screening programme are quite considerable, so that it cannot yet be recommended as a global cancer control policy. For countries where it may be feasible, the greatest benefit would be obtained by concentrating screening on women aged 50-69. Although randomized trials on breast self examination (BSE) and health worker breast examination (HWBE) are still ongoing, preliminary results have demonstrated both the feasibility of teaching women and health workers to perform the examination, as well as the detection of earlier stage cancers. As it will still take several years of follow-up to determine if indeed a reduced mortality survival benefit will be observed, it is recommended for countries with high or intermediate risk to consider implementing these practical methods now.
The breast cancer control programme Primary prevention The number of new breast cancer cases can be reduced by primary prevention, specifically by avoiding the "affluent diet" and the promotion of a healthy diet. The following key principles must be observed: • Avoid excessive fat: lower limit 10 per cent of energy, upper limit 30 per cent of energy. This is the level generally advocated to minimize the risk of cardiovascular disease. Include adequate amounts of vegetables, fruits, and whole grains with fibre in the diet; lower limit 400 grams per day Ensure energy balance and maintenance of ideal body weight by a combination of adequate exercise and a moderate calorie intake. -254-
•
•
•
Prevent contamination of foods by carcinogens such as aflatoxin and chemicals used as pesticides, and avoid adding to food substances such as nitrites and nitrates that may be carcinogenic or lead to the formation of carcinogens.
The important measures to be considered in promoting dietary modification are the following: • government action to recognize dietary factors in cancer etiology and consider the implications of this for the relevant ministries (especially health and agriculture); appropriate education on diet in schools; public education campaign about diet and adults; collaboration with representatives of the food industry (both production and service aspects) to ensure compliance with the nutritional objectives of the programme.
• • •
The main feature of a diet modification programme are summarized diagrammatically in Figure 16.1.
Secondary prevention - early detection Screening Secondary prevention of breast cancer is possible by means of mammography, breast self-examination (BSE), and health worker breast examination (HWBE).
Mammography Several randomized trials have clearly shown a benefit from mammography for women aged 50 years or older. Screened women are expected to achieve a survival benefit of around 30 per cent compared with unscreened women. When feasible, mammographic screening for women of 50 years and above should be done every two to three years. No benefit had been shown for women of less than 50 years.
-255-
Manual on the prevention and control of common cancers
Figure 16.1: Secondary prevention - screening of cancer of the breast Implementation Train health care workers to examine breast and teach selfexamination to women aged 40 years or over Ensure link between identification of abnormality and referral for diagnosis, treatment, and follow-up If mammography is affordable for diagnosis, train radiologists and radiographers, and establish quality control of films Establish policy to use mammography for screening only at 50-69 years
Detectable preclinical phase (DPCP)
Birth
Onset of sexual activity
Dysplasia
Carcinoma in situ
Invasive cancer
Death
Average age: 25 40 Screening here has not been shown to be effective ~8% of cancers 50 Screening here has maximum cost-effectiveness ~92% of cancers 60 65 years
Process measures >80% of women aged 40 years or over receive information on breast cancer screening >80% of primary health care workers informed about the guidelines for breast cancer screening Impact measure >80% of women aged aged 40 years or over receive a single physical examination and are taught breast self-examination >70% of women aged 50-69 years screened (for mammography programmes) Outcome measures >30% of breast cancer detected by screening Ratio of cancers detected at first screen three times expected incidence (for mammography programmes) Medium term: >15% reduction in proportion of cases of invasive breast cancer with advanced (stage II+) disease Long term: >15% reduction in breast cancer mortality Short term:
Source: National cancer control programmes, Geneva, WHO, 1995.
Mammographic screening is, however, costly and technologically intensive, and may not be implementable for most women worldwide. While no randomized trials have been completed on self examination and
-256-
health worker examination, these two methods have the potential of detecting lesions earlier than usual, and may have a survival benefit. Mammographic screening should: 1) focus on women 50 years and older, and 2) should not be introduced for screening unless the resources are available to ensure effective and reliable screening of at least 70 per cent of the target group in a highly organized setting. Attention must also be given to providing adequate quality control measures for this highly technical procedure. HWBE should be integrated with the cervical cytological screening programme, and the level of BSE sustained every time a woman has personal contact with health workers. The main features of a breast cancer screening programme are summarized diagrammatically in Figure 16.2.
Early diagnosis and curative treatment For most women, BSE offers the most practical method of early detection. Several studies have demonstrated the following: • •
The feasibility and effectiveness of a BSE education programme. A substantial increase in the number of cases of breast abnormalities detected. A shortening of the time between detection and visit to the doctor. A shift to an earlier stage of breast cancer diagnosis.
• •
In addition, a study in Finland and another in Canada have produced evidence suggesting that women who are competent in BSE and have access to physicians capable of diagnosing detected abnormalities have a reduced mortality rate from breast cancer. BSE should be part of an integrated women's health programme. Intensive person to person interaction is required for women to acquire and maintain the habit, so that personal responsibility for one's own health and improved relations between women and health workers are fostered.
-257-
Manual on the prevention and control of common cancers
Figure 16.2: Primary prevention - diet
Implementation Establish collaboration with agricultural interests at government and industry level Perform a sampling survey to identify current dietary practices Set up a threefold strategy based on the following:
Education Especially of schoolchildren from age 10 years Mass education of adults Link with other elements of a healthy lifestyle (e.g. exercise) Integrate with related messages (e.g. on heart disease) Use the influence of the media
Legislation Change agricultural support to reduce consumption of fat and increase that of fruit and vegetables Regulate food preservation and preparation Label food with details of nutrient content
National leadership Promote interdisciplinary and interministerial collaboration Promote domestic and international collaboration, by government, agricultural industry, and NGOs
Process measures >80% of schoolchildren aged 10 years and over receive education about good dietary practices >50% of adults receive publicity about diet and cancer each year >1 legislative measure concerned with diet and health implemented Impact measures >80% of schoolchildren aged 10 years and over aware of good dietary practices >50% of adults aware of link between diet and cancer Outcome measures >30% of adults actively practising dietary modification >30% of adults exercise at least 3.5 hours each week Medium term: reduction in incidence of diseases (cardiovascular disease, colon cancer) Long term: reduction in incidence of other cancers (breast, stomach) Short term:
Source: National cancer control programme, Geneva, WHO, 1995.
HWBE ought to complement BSE. Since another important component of an integrated women's health programme is screening for cervical
-258-
cancer with the cervical smear, HWBE should be done at the time the smear is taken. The starting age should be between 35-40 years. The diagnosis of breast cancer is through a biopsy. The majority of breast masses in women younger than 35 years are not malignant and can be observed. The general practitioner should, however, refer all women with breast masses to a physician skilled in the diagnosis and treatment of breast cancer. Lumps in women 35 years and older should be biopsied, as the age-specific incidence rates of breast cancer progressively increase from this point. Fine needle aspiration biopsy (FNAB) is an important diagnostic method. FNAB is a safe, simple and inexpensive procedure and is more acceptable than an open biopsy. Health workers can be trained to perform FNAB in the clinic. Appendix 10 shows the clinical staging classification of breast cancer. Modified radical mastectomy (MRM) has been the standard curative treatment for Stages I,II and IIIA breast cancer. The operation consists of a total mastectomy and axillary node dissection. Breast conservation procedures have similar survival results as MRM, and consist of excising the breast tumour plus an axillary lymph node dissection, followed by radiotherapy to the breast. Axillary nodal metastases is associated with significantly shorter survival. The probability of survival ten years after treatment among women without axillary nodal metastases is around 80 per cent, as compared to 60 per cent for axillary node-positive cases. Adjuvant therapy significantly prolongs survival if axillary nodes are positive, the type of adjuvant therapy depending on the woman's age or menopausal status. Adjuvant hormone therapy using tamoxifen results in a 20 per cent average reduction in annual mortality risk among women older than 50 years. For woman younger than 50 years the reduction with adjuvant chemotherapy is 17 per cent, and 25 per cent with adjuvant oophorectomy. There is no evidence that periodic laboratory or radiologic tests ("metastases work-up") in order to detect "early" asymptomatic metastases is of benefit, in survival or any other outcome parameter. Routine investigations in the follow-up of asymptomatic patients are not indicated, and investigations should be done only as needed in symptomatic patients.
-259-
Manual on the prevention and control of common cancers
Palliative treatment Breast cancer is a slow growing tumour, particularly in older women, and many patients with advanced disease benefit from active treatment. For locally advanced cases (IIIB) the probability of surviving five years is around 40 per cent. The aim of active palliative treatment is the longlasting relief of locoregional symptoms, and the combination of surgery and radiotherapy is standard treatment. The addition of systemic drugs had been reported to reduce local recurrence but has not prolonged survival. The quality of life of most women with symptomatic metastatic disease can benefit from active palliative treatment, with many having prolonged survival. Radiotherapy gives very good palliation for symptomatic bone, vertebral and CNS lesions. The first line systemic treatment of choice is hormone therapy and the patients who will most likely benefit have the following characteristics: • • • • • Long disease-free interval (at least two years) Metastases limited to bone and soft tissue Late premenopausal or postmenopausal status Prior response to endocrine therapy Tumour with an oestrogen or progesterone receptor (or both)
For those who do not have these characteristics, chemotherapy is used as an initial systemic treatment. Symptomatic treatment, particularly pain relief, is always given in conjunction with active treatment, or for those unable to receive active treatment.
-260-
What the health worker should do Health education The Core Cancer Health Education Module recommended for the Region (see Chapter 6 - Health education) includes 1) promoting awareness of the importance of a healthy diet in health promotion and the prevention of many noncommunicable diseases, including cancer, 2) helping individuals who have adopted unhealthy dietary habits to change to a healthy diet, 3) promoting the habit of breast self examination (BSE), and 4) in countries where there is a population-based screening programme (e.g. mammography for women 50 years or older), encouraging the target population to participate in the screening programme. Health education, aimed at the prevention and early detection of breast cancer, can, in some countries, consist of all four different categories of cancer health education - 1) increasing awareness, 2) changing risk behaviour, 3) learning self-examination skills, and 4) promoting participation in an early detection programme.
The following are the steps in performing BSE (Figure 16.3): Inspection • Remove clothing and view yourself standing in front of a mirror. Raise both arms above the head simultaneously, and look at your breasts as you do so (Figure 16.3A). Lower your arms, and again observe both breasts.
•
•
Figure 16.3A
-261-
Manual on the prevention and control of common cancers
•
Repeat arm raising and lowering, looking at your breasts from different angles. Place your hands on your hips and tighten your chest muscles by pressing down firmly on your hips, relax, then press again, repeating several times and looking closely at your breasts (Figure 16.3B).
•
Figure 16.3B
•
Be on the lookout for these warning signs during inspection lumps; change in size or shape; dimpling or puckering of the skin; nipple retraction; bleeding or discharge from the nipple.
Palpation • Lie down with a pillow or folded towel underneath your right shoulder. Place your right hand under your head. Use your left hand to examine your right breast. Placing your fingers flat over your breast, examine the breast in a vertical strip pattern, the first strip starting at your armpit.
• •
-262-
•
Make a circle of light, then firm pressure to feel for any lump or thickening (Figure 16.3C). Proceed towards the bra-line, making similar circles of light and firm pressure until every spot has been covered. Move your fingers 2 cm to the left and repeat the procedure, starting from the collar bone to the bra-line.
•
•
Figure 16.3C
•
Work up and down in 2 cm strips until you reach the breast bone (Figure 16.3D). Carefully examine the areola, and with both hands apply firm pressure on the right breast and see if any discharge comes from the nipple. Transfer the pillow to underneath your left shoulder, and put your left Figure 16.3D hand under your head. Examine your left breast with your right hand, using the same circles of light then firm pressure in a vertical strip manner.
•
•
•
For women who are still menstruating, BSE should be performed at least one week after the last day of menstruation, when the usual perimenstrual breast changes will have subsided.
-263-
Manual on the prevention and control of common cancers
Early Detection Health workers should take the opportunity to examine the breasts whenever women attend the clinic, particularly women 35 years and older. At the same time, BSE should be taught and the correct procedure reinforced. An opportune time is when a cervical smear is taken.
The following are the steps in performing HWBE (Figure 16.4): Inspection • Clothing above the waist is removed, and the patient either sits on the side of the examining table with the health worker standing in front of her, or, the patient sits on a chair with the health worker also sitting on a chair in front of the patient. As in BSE, the patient raises and lowers her arms, and alternately presses and relaxes her hands on her hips. The health worker should be on the lookout for the same warning signs.
•
•
Figure 16.4A
-264-
Palpation • The patient remains seated, and the examiner palpates each supraclavicular area, looking out for lymph nodes (Figure 16.4A). The examiner's right forearm then sup-ports the patient's right forearm which is flexed at the elbow. The examiner palpates the patient's left axilla, urging the patient to relax her right shoulder and right arm while supporting her right forearm, so as to facilitate palpation as deep into the axilla as possible in order to feel for enlarged axillary lymph nodes
•
•
Figure 16.4B
(Figure 16.4B).
• •
The procedure is reversed in palpating the left axilla. The patient then lies down with a pillow underneath her right shoulder and her right hand underneath her head. The examination proceeds in the same manner as in BSE, using circles of light then firm pressure with the fingers flat (Figure 16.4C) in a vertical strip pattern (Figure 16.4D), ensuring that the entire breast is examined.
•
-265-
Manual on the prevention and control of common cancers
Figure 16.4C
Figure 16.4D
• •
The nipple and areola area are palpated last. The procedure is repeated on the left breast.
Health workers should also be able to perform a diagnostic biopsy in the clinic. This is particularly important in areas where access to hospitalbased facilities is difficult, or when the reliability of patients actually going to hospital for a biopsy is questionable. A definite diagnosis is important, even if the biopsy specimen has to be sent to a remote facility for reading. Of great value is FNAB, which can be done as soon as a suspicious mass is detected.
The following are the steps in performing FNAB (Figure 16.5): • The patient lies down, and as in BSE and HWBE, with a pillow underneath the shoulder and the ipsilateral hand under the head. The skin over the mass is prepared with an antiseptic (i.e. povidone-iodine, chlorhexidine, hexachlorophene). The mass is fixed firmly with the thumb and index finger of one hand.
•
•
-266-
• •
No local anaesthetic is required. A sterile gauge 23 needle, attached to a sterile syringe, is used. The bigger the syringe the easier to generate negative pressure. Using the other hand, the needle is inserted into the mass percutaneously, and, applying negative pressure, by incomplete withdrawal of the syringe plunger. While maintaining the negative pressure, the needle is moved to and fro in different directions within the mass without pulling the needle from the skin puncture site (Figure 16.5).
•
•
Figure 16.5
•
The syringe tip is carefully observed to see if tissue, often mixed with serosanguinous fluid is aspirated. The needle is then withdrawn and the syringe plunger released before the needle exits the skin. A sterile gauze is placed on the puncture site and the patient is asked to apply firm pressure for at least 5 minutes using the contralateral hand.
•
•
-267-
Manual on the prevention and control of common cancers
•
The syringe plunger is withdrawn completely, reinserted, and the aspirated material squirted onto a glass slide. A second slide is used to produce a smear of the aspirated material, taking care not to make the smear too thin. The smear is allowed to dry and then immersed in a fixative (7090 per cent alcohol) for 10 minutes. The fixed slide is labelled with the name of the patient, place and date of the procedure. The fixed slide is sent to a processing and reading facility. If possible, the aspiration site is inspected the following day. Neither postoperative analgesics nor antibiotics are necessary.
•
•
•
• • •
-268-
References and suggested readings 1. Boyd N. Breast Cancer. In: Love RR (editor) Manual of clinical oncology. Sixth edition. International Union Against Cancer; Springer - Verlag 1994: 248-268. Eddy DM. Secondary prevention of cancer: an overview. Bulletin of the World Health Organization, 1986, 84(3): 421-429. Fleming ID, Cooper JS, Henson DE, Hutter RVP, Kennedy BJ, Murphy GP, O’Sullivan B, Sabin LH, Yarbro JW (editors) AJCC Cancer Staging Manual. Fifth edition. American Joint Committee on Cancer; Lippincott-Raven, 1997. Love RR, Koroltchouk V. Tamoxifen therapy in breast cancer control worldwide. Bulletin of the World Health Organization, 1993, 71(6): 795-803. Miller AB. Mammography: a critical evaluation of its role in breast cancer screening especially in developing countries. Journal of Public Health Policy, l989, 480-498. National cancer control programmes: policies and managerial guidelines. Geneva, World Health Organization, 1993. Nystrom L, Rutqvist LE, Wall S et al. Breast cancer screening with mammography: overview of Swedish randomized trials. Lancet, 1993, 341: 973-978. Pisani P, Parkins DM, Muñoz, Ferlay J. Cancer and infection: estimates of the attributable fraction in l990. (submitted for publication). Semiglazov VF, Moisenko VM. Breast self examination for early detection of breast cancer: a USSR/WHO controlled trial in Leningrad. Bulletin of the World Health Organization, 1987, 65(3): 391-396.
2. 3.
4. 5.
6. 7.
8. 9.
10. Tomatis L. (editor) Cancer: causes, occurrence and control. Lyon, International Agency for Research on Cancer, 1990 (IARC Scientific Publications, No. 100). 11. Van Parijs LG. Public education in cancer prevention. Bulletin of the World Health Organization, 1986, 64(6): 917-927. 12. Veer PV, Kok FJ, Brants HA, Ockhuigen T, Sturmans F, Hermus RJ. Dietary fat and the risk of breast cancer. International Journal of Epidemiology, l990, l9(1): 12-18.
-269-
17. Cervical cancer Magnitude, cause and prevention Magnitude
I
n 1980, cervical cancer was the fifth most common cancer worldwide and comprised 7.3 per cent of all cancers. It was the second most common among females after breast cancer, and made up 15 per cent of all cancers in women. Cases in developing countries were almost four times more numerous than in developed countries. There are large variations in rates between ethnic groups within countries. Rates are higher in urban areas. Wives of clergymen had only 12 per cent of the rates of cervical cancer in other women of the same age, while rates in wives of seamen and fishermen were 160 per cent more. These wide variations can be attributed to two major factors: 1) differences in sexual practices; and 2) differences in access to organized cervical cancer screening programmes. Incidence and mortality have generally been declining in countries where an organized screening programme exists, the greatest declines observed in the age groups that are maximally screened. Incidence and mortality are increasing in countries where there are no organized screening programmes, which is the case in most developing countries.
Cervical Cancer
Table 17 shows the 1990 estimated age-standard rates (ASR) in ten countries and one area in the Western Pacific Region. Table 17. Cervical cancer: age-standardized incidence rates (ASR) per 100 000 in ten countries and one area in the Western Pacific Region (1990 Estimates, Reference 9). Country/Area Australia China Hong Kong Japan Malaysia New Zealand Papua New Guinea Philippines Republic of Korea Singapore Viet Nam ASR 11.03 14.68 18.6 15.36 12.2 14.76 46.21 15.09 21.35 23.64 34.16 % ALL CANCERS 4.59 7.15 8.50 8.97 8.45 5.17 24.83 10.61 14.37 11.96 17.93
The highest estimated ASR was in Papua New Guinea and the lowest in Australia. Comparatively low rates were also estimated for China, Japan, the Philippines, New Zealand and Malaysia. Intermediate rates were estimated for the Republic of Korea, Singapore, Viet Nam, and Hong Kong. The peak age for incidence of cancer of the cervix is between 40 and 60. A small percentage occur below 30. Most recent reports, however, indicate that in some countries in the region incidence among the young is increasing. The incidence rate becomes significantly high between 30 and 35, increases further to its peak at about 50, and steadily declines after 60.
-271-
Manual on the prevention and control of common cancers
Cause Risk factors for cancer of the cervix include multiple sexual partners on the part of both the man and the woman, early age at first coitus, multiparity, a history of sexually transmitted infections, and a history of such infections in male sexual partners. Among sexually active women, a positive correlation has been established between the incidence of cancer of the cervix and the sexual partner's occupation, extramarital sexual activity and cancer of the cervix in previous sexual partners. There is overwhelming epidemiological evidence that cancer of the cervix is caused by an infectious agent that is transmitted through sexual intercourse. Several viruses have been implicated. The focus of current attention is human papilloma virus (HPV). HPV is the virus responsible for condyloma acuminata or "venereal wart" or "genital wart" commonly seen in the vulva, vagina and perineum. In the cervix, the lesion is less obvious. It has thus been called "flat condyloma" or "subclinical human papilloma virus infection". Characteristic cytological, colposcopic and histological findings generally result from this infection. It has been observed that the incidence of cervical condyloma is high in population groups with a high incidence of cervical cancer and its precursors. It has also been observed that there are definite relationships between the mean ages of patients with cervical condyloma, cervical cancer precursors and cervical cancer. In the laboratory, HPV DNA has been demonstrated in cervical cancer cells in a significant number of cases.
Pathology Following inoculation of the virus during sexual intercourse, it reaches the basal layers of the cervical squamous epithelium and establishes a colony there. Not all inoculated women become persistently infected, depending on individual host resistance factors. There is no clinical manifestation at this time and the histological changes in the cervix indicative of malignancy are limited to the basal layers of the epithelium. This lesion is called cervical intraepithelial neoplasia, grade I or CIN I. When these histological changes involve two-thirds of the total thickness of the epithelium, the lesion is referred to as cervical intraepithelial neoplasia grade II or CIN II. When they involve the whole -272-
Cervical Cancer
thickness of the epithelium, the lesion is referred to as cervical intraepithelial neoplasia, grade III or CIN III. CIN III incorporates both severe dysplasia and the old "carcinoma-in-situ". CIN III is the most severe of the precursor lesions. It precedes invasive cancer. All of these lesions have the potential to progress to invasive cancer. However, not all of them actually do progress. Some are still reversible. Reversibility is highest in CIN I and lowest in CIN III. Progression to invasive cancer is highest in CIN III and lowest in CIN I. The rate of progression also varies greatly. In general, it takes years rather than months for these epithelial abnormalities to become invasive cancer. The generally accepted time interval for this change to occur is 5 to l5 years. In its original location in the cervix, usually the squamo-columnar junction, the tumour grows and soon becomes clinically evident. It is at this stage that the first symptoms usually appear. The most common symptom is vaginal bleeding, intermenstrual and, classically, postcoital. From the cervix, it spreads 1) by direct extension, 2) through the lymphatic system, and 3) through the blood stream. The most common routes of direct extension are laterally to the parametria-cardinal and uterosacral ligaments, inferiorly to the vagina, and superiorly to the corpus uteri. In the late stages, it may spread anteriorly to the urinary bladder and/or posteriorly to the rectum. Initially, it causes bleeding from these organs. Subsequently it may cause obstruction and even fistula formation. When the cancer gains access to the lymphatic vessels in the cervical stroma and the parametria, the pelvic lymph nodes may be involved, as well as the upper lymph node chains. Spread through the blood stream may explain the occurrence of metastases in distant sites like the lungs and the brain. With parametrial involvement, ureteral obstruction occurs. The resulting hydronephrosis, pyelonephritis, and non-functioning kidneys, if uncorrected, can lead to uraemia which is the most common cause of death among patients with cervical cancer. Other causes of death are haemorrhage and infection. With parametrial involvement of varying degrees, obstruction of the lymphatics and veins draining the lower extremeties also occurs. This results in oedema of the lower extremeties. Sometimes, the vulva also becomes oedematous. Sometimes, bone and spinal nerve roots become involved even before the onset of uraemia. When this occurs, pain becomes a very prominent symptom. In this terminal stage, the clinical picture is classic, characterized by 1) pain in the lower back, hips or thighs, 2) oedema of the lower extremities and 3) evidence of ureteral obstruction. These constitute the "ominous triad" in cancer of the cervix. -273-
Manual on the prevention and control of common cancers
Prevention Primary Prevention Since there is almost universal acceptance that a sexually- transmitted agent is the major cause of cervical cancer, primary prevention must entail a consideration of the following: 1) a monogamous sexual relationship between husband and wife; 2) a delay in the onset of sexual activity; and 3) the use of barrier contraceptives. Mechanical barriers include condoms (for male and female) and diaphragms. Primary prevention involves a major change in sexual practices and attitudes. This change is very difficult to effect and it takes a long time to involve the majority of the population. Nevertheless, primary prevention concepts should be incorporated into both adult and adolescent health education. These educational programmes need to be culturally sensitive but should emphasize the responsibility of men in reducing the risk of subsequent disease in their partners, as well as that of women themselves. There is a need to educate males from adolescence. This should be linked with programmes on the prevention of AIDS and other STDs.
Secondary Prevention Most cases are asymptomatic for a long period. Therefore secondary prevention through screening is currently the most important component of cervical cancer control. Screening is to detect lesions (precursor lesions or early invasive cancer) at a time when the presence of the disease is not recognized. The women may have symptoms but may not appreciate them as due to the disease. At the present time, the most reliable and most practical screening method for cancer of the cervix and its precursors is the Papanicolau smear. It is based on the biological phenomenon that cells are continuously shed from epithelial surfaces. Both normal and abnormal (atypical, malignant) cells are shed. If these cells are properly collected, fixed and stained, accurate interpretation can be made and very useful information can be obtained regarding the epithelium from which they came.
-274-
Cervical Cancer
Screening for cancer of the cervix is intended to discover preinvasive lesions. If these lesions are appropriately treated, their progression to invasive cancer is prevented. Sometimes, with screening, invasive cancer is discovered. This is generally at an early stage and, when appropriately treated, the prognosis is very good. Considering the effectiveness of the Pap smear in detecting cervical cancer precursors, and considering the great number of women at risk of developing cervical cancer, public health education on cancer of the cervix should emphasize, among other things, that the development of invasive cancer can be prevented with effective screening. Public education messages should emphasize the effectiveness and availability of cervicovaginal cytological and auxillary diagnostic procedures to follow up abnormal results. Necessarily, treatment facilities should be available and accessible to the target population. Public information may be effected through radio, television, movies and the print media, including pamphlets and posters. Direct personal communications with knowledgeable and respected members of the community, the health care providers and the community leaders, are very important. It is also important that proper sterilization methods are strictly implemented for reusable vaginal specula to assist in the prevention of HPV infection. Disposable specula should not be reused.
-275-
Manual on the prevention and control of common cancers
The cervical cancer control programme Primary prevention Cervical cancer incidence can be significantly decreased by both primary and secondary prevention. Primary prevention consists of safe sexual practices, including barrier methods to prevent the transmission of the viral agent(s). Health education on safe sexual practices should be integrated with other important national health activities such as the control of sexually transmitted diseases (STDs), AIDS and population control.
Secondary prevention - screening Prevention of invasive cancer is accomplished through a cervical cytological screening programme (Pap smear). The target age group and screening frequency has to be determined by each country, and will depend on epidemiological, sociocultural and economic factors, taking into consideration all the activities to be carried out following the reading of an abnormal smear. The main features of a cervical cytology screening programme are summarized diagrammatically in Figure 17.1. For cervical cancer screening to be effective, it should target as many women as possible. In general, re-screening is not as important as increasing the number of women screened. For this reason, the following managerial guidelines are recommended: 1) A central/national registry should be kept. This should contain accurate basic information on all women screened, including date and result of screening. If a result is abnormal, action taken should also be recorded.
-276-
Cervical Cancer
Figure 17.1:Secondary prevention - cytology screening for cancer of the cervix Implementation Establish health education for awareness of screening Establish a clear policy to screen women >35 years of age Identify women aged 35-59 years Train primary health care workers to examine cervix and take smears Train cytotechnicians and cytopathologists Establish laboratories with quality control Ensure link between identification of abnormalities and referral for diagnosis, treatment, and follow-up Establish information system for monitoring and evaluation
Detectable preclinical phase (DPCP)
Birth
Onset of sexual activity
Dysplasia
Carcinoma in situ
Invasive cancer
Death
Average age: ~13 18 Screening here encounters the dysplasia swamp ~8% of cancers 35 Screening here has maximum cost-effectiveness ~92% of cancers 50 55 years
Process measures >80% of women aged 35-59 years informed about screening for cancer of the cervix >80% of primary health care workers instructed in taking cervical smears Impact measure >80% of women aged 35-59 years screened at least once Outcome measures >30% reduction in proportion of cases of invasive cervical cancer with advanced (stage II+) disease Medium term: >30% reduction in incidence of invasive cervical cancer Long term: >30% reduction in cervical cancer mortality Short term:
Source: National cancer screening programmes. Geneva, WHO, 1996
-277-
Manual on the prevention and control of common cancers
2) The screening programme should not be isolated but integrated into the primary health care services. 3) Screening facilities should be decentralized and located near the main centres of population. The following may be utilized: 1) health centres, 2) lying-in clinics, 3) family planning clinics, 4) STD clinics, 5) hospital outpatient services, 6) mobile units, and 7) private doctors' offices. Rarely will it be necessary to establish a new facility for smear collection. 4) The screening facilities should be available during hours that are convenient for women, especially working women. 5) Allied health workers should be utilized in the screening programme. They should be given adequate training in speculum examination, obtaining cervical smears and recognition of deviations from normal appearance. 6) Screening personnel should be client-oriented. All efforts should be exerted to make the client feel at ease. 7) Briefing should be done by a specially trained member of the screening team. This briefing should include information on the benefits as well as risks of false-positive and false-negative results. 8) Screening procedures should be free or very inexpensive. 9) The cytology laboratory should be centralized to ensure strict quality control. Cytoscreeners should not be constantly changing since experience enhances the accuracy of reading. 10) Arrangements should be made for the efficient transport of slides, clinical data and results. 11) Results should be reported promptly. 12) Cervical cytology must be integrated into a system of diagnostic and therapeutic services such as • • • •
colposcopy/Schiller's test and biopsy; gynaecological pathology; gynaecological therapy; and radiation therapy.
-278-
Cervical Cancer
13) Relevant data should be fed into a system of regional and national statistics to help in the monitoring and evaluation of the programme. 14) Appropriate resources should be tapped to sustain the programme.
When should screening be started, and how often? Quantitative studies have shown that, after one negative cytological smear for cervical cancer, screening once every five years accomplishes about the same effect among women 35-64 years of age as screening every year. Even screening once every ten years yields a reduction of almost twothirds in the incidence of invasive cervical cancer. This evidence led a WHO meeting to conclude that countries with limited resources should aim to screen every woman once in her lifetime between 35 and 40 years. When more resources are available, the frequency of screening should be increased to every ten and then every five years for women aged 35-64 years. In the national cancer control programme, the aim should be to screen every woman aged 35-40 once, wherever laboratories to examine the smears and facilities for treatment of abnormalities are available. When 80 per cent of women aged 35-40 years have been screened once, screening frequency should increase to ten years and then five years for women aged 35-64 years, as resources permit. In most developing countries in the Region, the proportion of younger women is higher than that in developed countries, and it is recommended that the target population are women aged 30-59 years. Women of low socioeconomic status are at higher risk.
Who should take the Papanicolaou smear? Virtually anyone who is tasked with the delivery of women's health care should be able to take the smear with proper training - the gynaecologist-obstetrician, general physician, midwife, nurse or traditional birth attendant. The gynaecologist-obstetrician will probably not need any special training because the procedure is basic to gynaecology. The general physician will need a short review of the technique of inserting the vaginal speculum as well as the topographic anatomy of the cervix and the vagina, as will the midwife and the nurse. The traditional birth attendant will need
-279-
Manual on the prevention and control of common cancers
more intensive training. The non-gynaecologist will also need to acquire competency in recognizing gross deviations from the normal appearance of the cervix. Certain abnormalities may require biopsy.
What is necessary in the collecting centres/clinics? 1) An examining table where the women can be placed in the dorsal lithotomy or lateral position. This may be improvised. 2) Provision for privacy. 3) A good source of light. 4) Vaginal specula. 5) Sterilization facilities. 6) Materials: • • • • •
glass slides; pencil to identify slides; fixative like 95 per cent alcohol, equal parts of 95 per cent alcohol, ether and spraycyte; Ayre spatula; and forms for entering relevant data.
The volume of specimens should be sufficient to justify the employment of at least two cytoscreeners, to ensure that quality control programmes can be put in place. Adequate volume ensures the occurrence and recognition of abnormalities.
Cytology laboratory For purposes of effective quality control, the cytology laboratory must be centralized. It should be manned by: 1) A cytopathologist who acts as director of the laboratory and is responsible for the final cytological diagnosis of all specimens received. He/she plans and implements strategies for quality control.
-280-
Cervical Cancer
2) A cytotechnologist who acts as cytoscreener and supervisor of the cytotechnician. 3) A cytotechnician who prepares the slides -- sorts, fixes and stains them for reading by the cytotechnologist. He/she also cleans and maintains the microscope and other laboratory equipment. 4) A secretary who must be computer literate. He/she performs all the secretarial duties in the laboratory -- receiving the specimens (and requests), recording them, typing the results, sending them out and filing copies in the laboratory. The laboratory may be hospital-based to avoid the problem of too much initial financial outlay. It must be well lit and well ventilated and must have sufficient space for microscopic work, slide preparation, slide and report filing, and administrative, teaching and research activities. Cytology reports should not only be accurate but promptly communicated.
Secondary prevention - early diagnosis Early diagnosis and curative treatment Although a cervical cytological screening programme is the ideal method of reducing mortality through secondary prevention, this can be supplemented by earlier diagnosis of symptomatic cases. In countries where a cytological screening programme is not yet feasible, the following early detection measures will help considerably: • encouraging and training health professionals to be alert to the signs and symptoms of cancer; instituting campaigns to make the public aware of the symptoms of the disease and of the benefits of early diagnosis; where appropriate, introducing measures to promote early diagnosis of common cancers that are potentially curable if diagnosed early.
•
•
The main features of early detection for cancer of the cervix are summarized diagrammatically in Figure 17.2.
-281-
Manual on the prevention and control of common cancers
Figure 17.2: Secondary prevention - downstaging for cancer of the cervix Implementation Establish health education for awareness of the disease Establish a clear policy to examine women >35 years of age Identify women aged 35-59 years Train primary health care workers to examine cervix and identify abnormalities Ensure link between identification of abnormality and referral for diagnosis, treatment, and follow-up Establish information system for monitoring and evaluation
Detectable preclinical phase (DPCP)
Birth
Onset of sexual activity
Dysplasia
Carcinoma in situ
Invasive cancer
Death
Average age: ~13 18 Examinations here unlikely to find cancers ~8% of cancers 35 Examinations here are cost-effective 50 55 years
~92% of cancers
Process measures >80% of women aged 35-59 years received education on cancer of the cervix >80% of primary health care workers informed of the benefits of downstaging for cancer of the cervix Impact measure >80% of women aged 35-59 years examined at least once Outcome measures Short term: >30% of cervical cancers discovered by examination Medium term: >30% reduction in proportion of cases of invasive cervical cancer with advanced (stage II+) disease Long term: >30% reduction in cervical cancer mortality
Source: National cancer control programmes, Geneva, WHO, 1996
-282-
Cervical Cancer
The most important symptom of cancer of the cervix is vaginal bleeding which can be postcoital and/or intermenstrual. This occurs even in the very early stages of the disease. Foul smelling vaginal discharge may also be an early symptom. Pain is not an early symptom. Symptomatic women should have an initial speculum examination of the cervix as soon as possible.
Physical findings Classic physical findings include: 1) A fungating or cauliflower-like mass arising from either lip or all of the cervix, which bleeds easily when touched. There may be necrotic areas. 2) An ulceration, often with raised and indurated edges, also involving either the lip or all of the cervix. It also bleeds easily. There may also be necrotic areas. 3) Roughening or "erosion" around the external os. may not bleed when touched. This may or
Procedural considerations Some important procedural considerations are: 1) No oily lubricant should be used. If the vagina is dry (as in elderly women) and insertion of the speculum produces pain, normal saline solution, or even water, may be used. 2) No sexual intercourse should be engaged in for at least 24 hours before the procedure. This is not absolute. 3) No bleeding should be evident. This is also not absolute. While the abundance of red blood cells may mask abnormal/malignant cells, exfoliation may be greatest at the time of bleeding. Occasionally, the growth of the tumour may be towards the endocervix. In this case, while the ectocervix may be smooth and unremarkable, the entire cervix may be felt to be bulky or barrel-shaped, particularly on rectal examination.
-283-
Manual on the prevention and control of common cancers
Management of abnormalities It is the responsibility of primary-health-care workers to ensure that those women discovered to have an abnormality on cervical smear or on visual inspection of the cervix are referred for appropriate diagnosis and management. This can be one of the major points of failure for cervical cancer screening programmes. In the early cases, when the lesion is not obvious, the following steps are taken. Following an abnormal cervical cytological result, colposcopy is performed and biopsy taken from the most serious looking area. For those classified cytologically as CIN I, a repeat smear at six months is appropriate, with referral for colposcopy only if there is evidence of cytological progression. If the abnormal area can be seen in its entirety, the result of biopsy may be taken as definitive. If the upper margin of the abnormal area cannot be seen (i.e., if this extends into the cervical canal) endocervival curretage is performed. If endocervical curettage shows malignancy, conization is performed to establish the presence or absence of invasion. The cervix is very strategically located. It is very accessible to the examining finger and routine diagnostic procedures. The staging (measurement of the extent of spread) of cancer of the cervix is clinical. It is based on the findings following a careful physical examination that is primarily focused on the pelvis, and certain diagnostic procedures like colposcopy, endocervical curettage, conization, cystoscopy, intraveneous pyelography, proctosigmoidoscopy, biopsy of inguinal or supraclavicular nodes (when suspicious), chest X-ray and bone survey. Computerized tomography scanning and magnetic resonance imaging, though effective in detecting metastases, are still very expensive and of limited availability. Their use in clinical staging is not routine. The original clinical stage record is retained regardless of subsequent developments, such as the finding of more extensive disease on definitive surgery. This is very important in reporting incidences by stage of the disease and evaluating the results of treatment. The International Federation of Gynaecologists and Obstetricians (FIGO) has adopted the clinical staging of cancer of the cervix shown in Appendix 11. The pelvic examination should preferably be done under anaesthetic. However, since this cannot be easily implemented, anaesthesia, except in very rare circumstances, is not required.
-284-
Cervical Cancer
Treatment of invasive cancer At the present time, the treatment of choice for patients with invasive cancer of the cervix is radiation. It is, in general, applicable to all stages of the disease, from stage I to stage IV. In young, good-risk patients with early stages of the disease up to Ila, surgery, in the form of radical hysterectomy and bilateral pelvic lymphadenectomy, is equally effective. Both external and intracavitary radiation are used. By a proper combination of the two, an ideal dose distribution to the pelvis is achieved. In the early stages, when most of the disease is still centrally located, the treatment is principally intracavitary radiation, supplemented laterally by external radiation. As the disease progresses and spreads peripherally, there is a gradual shift in emphasis in favour of external radiation. Radical hysterectomy and bilateral pelvic lymphadenectomy is an alternative treatment for stages Ib and IIa. It is performed on young, goodrisk patients. It has the advantage of allowing for direct assessment of spread (surgical staging), easier preservation of ovarian function (in radical hysterectomy, the ovaries may be preserved) and maintaining the integrity of the vaginal epithelium. Radical hysterectomy entails removal of the whole uterus, usually both tubes and ovaries, a wide portion of the parametria almost to the pelvic wall, and the upper half or two-thirds of the vagina. The search continues for effective systemic therapies that will show reduced mortality or even improved locoregional control.
Palliative treatment In the late stages, when the tumour involves bone or spinal nerve roots, pain becomes a major problem, particularly the severe hip and leg pains unique to the terminal stages of this disease. In many countries, the recommendation of the World Health Organization for cancer pain control has been adopted. It is effective, simple and inexpensive. It consists of oral administration of drugs "by the clock" rather than "on demand". With certain modifications, drugs are progressively increased from non-opioids to mild opioids to strong opioids.
-285-
Manual on the prevention and control of common cancers
What the health worker should do Health Education The Core Cancer Health Education Module recommended for the Region (see Chapter 6 - Health education) includes 1) promoting cancer awareness of safe sexual practices that will prevent the transmission of the infectious agent that causes cervical cancer, and the ability of the cervical cytological test (Pap smear) to detect early cervical cancer, and 2) persuading the target population to participate in a population-based cervical cytological screening programme when this is in place.
Early Detection The following are the steps in taking a cervical smear: 1) After preliminary counselling, the woman is placed in the dorsal lithotomy position and properly draped. 2) After examining the vulva, the vaginal speculum is inserted. If a bivalve speculum is used, the blades must initially be side by side (i.e., the long diameter of the instrument must be aligned with the antero-posterior diameter of the introitus). As the instrument is gently pushed in, it is rotated so that when fully inserted, the blades are directly against the anterior and the posterior vagina. Care should be taken that pressure is consistently on the posterior vagina. If necessary, the lower vagina is gently pressed with one or two fingers to make insertion more comfortable. The blades are separated only when the instrument is fully inserted. 3) With a good source of light, the cervix, in its entirety, is visible. Gross abnormalities, including bleeding, and/or discharge, are noted.
-286-
Cervical Cancer
4) A wooden (or plastic) Ayre spatula is inserted, with the longer tip at the external os. This is rotated 360 degrees in a sweeping/scraping motion. No portion of the squamo-columnar junction should be spared. 5) The material that sticks to the spatula is then spread thinly and evenly over a wide area of a clean and pre-labelled glass slide. The spatula is held parallel to the slide to effect an even distribution of the cellular material. The glass slide may be pre-cleaned with acetone, ether, xylol or alcohol. The procedure of spreading the material over the glass slide is the same as if a tongue depressor was used. If a cotton tipped applicator is used it is rolled over the glass slide. 6) After the smear is made, the slide is immediately dipped in or sprayed with fixative. It should not be allowed to dry. 7) The speculum is gently removed, again with a gentle rotating motion and with pressure being applied more to the posterior vagina. 8) After checking the labelling, the slide is sent to the processing laboratory. 9) A disposable speculum is discarded, or a reusable speculum is properly sterilized. To increase the accuracy of the smear, certain precautions prior to the procedure must be observed: 1) No internal examination should be performed. 2) No vaginal douche should be given. Symptomatic women (e.g. postcoital or intermenstrual vaginal bleeding, foul vaginal discharge) should have an examination as soon as possible. The examination is the same as in taking the cervical smear. If a lesion is seen which looks suspiciously like cervical cancer, a health worker may perform a punch biopsy of the lesion. If not, the patient should be referred accordingly.
-287-
Manual on the prevention and control of common cancers
Palliative care The most distressing complaint of women with advanced cervical cancer is pain, mostly localized to the pelvic area. Fortunately the majority can be satisfactorily relieved by following the WHO Method of cancer pain relief. Terminal uraemia is often welcomed as the patient's suffering diminishes, and priority should be given to providing psychosocial and spiritual support for the patient and her family.
-288-
Cervical Cancer
References and suggested readings 1. 2. 3. 4. Eddy DM. Secondary prevention of cancer: an overview. Bulletin of the World Health Organization, l986, 84(3): 421-429. Control of cancer of the cervix uteri. Organization, l986, 64(4): 607-618. Bulletin of the World Health
Cytological screening in the control of cervical cancer: technical guidelines. Geneva, World Health Organization, l988. Fleming ID, Cooper JS, Henson DE, Hutter RVP, Kennedy BJ, Murphy GP, O’Sullivan B, Sabin LH, Yarbro JW (editors) AJCC Cancer Staging Manual. Fifth edition. American Joint Committee on Cancer; Lippincott-Raven, 1997. Hakama M, Miller AB, Day NE (editors) Screening for cancer of the uterine cervix. Lyon, International Agency for Research on Cancer, l986 (IARC Scientific Publication No. 76). Miller AB. Cervical cancer screening programmes: managerial guidelines. Geneva, World Health Organization, l992. Muñoz, Bosch FX, Jensen OM (editors ) Human Papillomavirus and cervical cancer. Lyon, International Agency for Research on Cancer, l989 (IARC Scientific Publications No. 94). National cancer control programmes: policies and managerial guidelines. Geneva, World Health Organization, l993. Pisani P, Parkin DM, Muñoz N, Ferlay J. Cancer and infection: estimates of the attributable fraction in l990. (submitted for publication).
5.
7. 7.
8. 9.
10. Stjernsward J, Eddy D, Luthra U, Stanley K. Plotting a new course for cervical cancer screening in developing countries. World Health Forum, l987, 8:42-45. 11. Tomatis L (editor) Cancer: causes, occurrence and control. Lyon, International Agency for Research on Cancer, l990 (IARC Scientific Publications No. l00). 12. Ulmer HU, Hossfeld DK. Love RR. Cancer of the uterine cervix and endometrium and gestational trophoblastic disease. In: Love RR (editor) Manual of clinical oncology. Sixth edition. International Union Against Cancer, Springer-Verlag; l994: 369-386.
-289-
Manual on the prevention and control of common cancers
13. Van Parijs LG. Public education in cancer prevention. Bulletin of the World Health Organization, l986, 64(6): 917-927.
-290-
Glossary Active treatment (Anticancer treatment) treatment which removes or destroys cancer cells (e.g. surgery, radiotherapy, chemo-therapy), in contrast to palliative treatment which aims to relieve symptoms without necessarily affecting the cancer cells. active treatment intended to improve survival following curative treatment (e.g. adjuvant chemotherapy following mastectomy for curable breast cancer). any of several mycotoxins that are produced by molds in stored grain and food meals (e.g. corn). prepared usually by smearing the betel leaf with slaked lime and ground pieces of areca nut. Crushed leaves of cured tobacco may be added. The ingredients are folded in the betel leaf and chewed. a form of radiotherapy that delivers local irradiation from sources in contact with or near target tissue. It can be intracavitary (e.g. cervix cancer), or interstitial (e.g. breast cancer), and given through implants, molds, seeds, needles and applicators. a processed foodstuff made of grains. examination of the tissues of the cervix and vagina by means of an instrument (coloscope) with a magnifying glass. these are the most available and cheapest sources of energy that can be used by man, and are contained in grains and other staples such as potatoes and yams. the microscopic examination of cells, usually contained in fluid in normal body secretion. cellular deviations from the normal in the
Adjuvant therapy
Aflatoxin Betel-quid
Brachytherapy
Cereal Colposcopy
Complex carbohydrates
Cytology
Dysplasia
Manual on the prevention and control of common cancers
epithelium, carcinoma. Epidemiology Genome Grains
and
considered
a
precursor
to
the study of the distribution and determinants of disease. the complete set of genes of an individual organism. the seeds or fruits of various food plants. In commercial and statutory usage includes other plants (e.g. soybean). individuals who are unable to get rid of the virus. They develop chronic hepatitis that often leads to cirrhosis and a high risk of primary liver cancer. the microscopic examination of tissues removed from the suspected cancer itself or from its spread. abnormal increase in the number of normal cells in normal arrangement in a tissues. the fruits or seeds of a wide variety of herbs, shrubs and trees bearing nodules on the roots that contain nitrogen-fixing bacteria (e.g. peas, beans). a widely cultivated annual leguminous plant with flat edible seeds. a radiological technique which can detect preclinical breast cancer (i.e. before the cancer is palpable). in relation to the Single Convention on Narcotic Drugs, 1961, in which the term is used in a legal sense (and not in a pharmacologocal sense) includes substances that are not narcotics, from a pharmacological sense (e.g. marijuana, cocaine) refers to morphine, codeine and other natural and synthetic drugs whose effects are mediated by specific receptors in the central and peripheral nervous sysytems. affording relief, but not cure.
Hepatitis B carriers Histology Hyperplasia Legumes
Lentils Mammography
Narcotic
Opioid
Palliative
Physical dependence
the neuroadaptation of the body to the presence of an opioid, and characterized by the onset of acute symptoms and signs of withdrawal if the opioid is -292-
Glossary
stopped or an opioid antagonist is administered. Precancerous lesions which eventually become cancerous if the initiating factor is not removed (e.g. oral leukoplakia in betel quid chewers). decreasing the incidence (new cases) of cancer by means of avoiding the risk factors most of which are environmental, such as smoking and unhealthy diet. decreasing the mortality from cancer by means of early detection and treatment. a behavioural pattern characterized by a craving for the mood-altering effects of a drug, and an overwhelming preoccupation with obtaining and using the drug. the edible seeds of many leguminous crops (e.g. peas, beans, lentils). the clinically detectable re-appearance of cancer in an individual, following a period after active treatment when the cancer cannot be detected. Recurrence can be local or distant. a period during which cancer cannot be clinically detected in an individual, usually following active anticancer treatment. a test for early squamous cell cancer using iodine solutions on the suspected area. Normal epithelium turns brown, while cancerous tissue turned white or yellow. Cancer cells do not contain glycogen and do not stain with iodine. testing asymptomatic detection of cancers. individuals for early
Prevention, primary
Prevention, secondary Psychological dependence (drug addiction) Pulses Recurrence
Remission
Schiller's test
Screening Tolerance
increased resistance to the usual effect of a drug as a result of long-term continuous use. Results in the need for higher doses to achieve the same pharmacological effect. short, fleshy underground stems o f some plants, some of which are edible (e.g. potato, taro, yam, cassava). made of entire ground grain kernels, in contrast to
Tubers
Whole grain
-293-
Manual on the prevention and control of common cancers
processed grains which lose many nutritional contents during processing.
-294-
Appendices: Appendix 1: Appendix 2: Appendix 3: Appendix 4: Appendix 5: Appendix 6: Appendix 7: Appendix 8: Appendix 9: Appendix 10: Appendix 11: Population - based cancer registries which are members of the International Association of Cancer Registries Antineoplastic and immunosuppressant drugs and drugs used in palliative care Clinical staging of oral cancer Clinical staging of nasopharyngeal cancer Clinical staging of oesophageal cancer Clinical staging of stomach cancer Clinical staging of colonic and rectal cancer Clinical staging of liver cancer Clinical staging of lung cancer Clinical staging of breast cancer Clinical staging of cervical cancer
Manual on the prevention and control of common cancers
Appendix 1 Population - based cancer registries which are members of the International Association of Cancer Registries Australian Paediatric Cancer ACT Cancer Registry Northern Territory Cancer Registry Queensland Cancer Registry South Australian Cancer Registry Tasmanian Cancer Registry Victoria Cancer Registry Western Australia Cancer Registry Beijing Cancer Registry Qidong Cancer Registry Shanghai Cancer Registry Tianjin Cancer Registry Zhongshan Cancer Registry Fiji Cancer Registry Registre du Cancer Health Statistics Department of Child Health Epidemiology and Population Health Epidemiology and Statistics Branch Epidemiology and Prevention Unit (NCD) S. Australian Health Commission Menzies Centre for Population Health Research CHIL GEN GEN POPU POPU POPU AUSTRALIA AUSTRALIA ACT AUSTRALIA Northern Territory AUSTRALIA Queensland AUSTRALIA South Australia AUSTRALIA Tasmania AUSTRALIA Victoria AUSTRALIA Western Australia CHINA Beijing CHINA Qidong CHINA Shanghai CHINA Tianjin
GEN GEN
POPU POPU
GEN
POPU
GEN GEN
POPU POPU
Department of Cancer Epidemiology Qidong Liver Cancer Institute Shanghai Cancer Institute Department of Epidemiology & Biostatistics Cancer Research Institute of Zhongshan City Ministry of Health Direction de la Sante Publique
GEN GEN GEN GEN
POPU POPU POPU POPU
GEN
POPU
CHINA Zhongshan City FIJI FRENCH POLYNESIA
GEN GEN
POPU POPU
-296-
Manual on the prevention and control of common cancers
Hong Kong Cancer Registry Aichi Cancer Registry Fukui Cancer Registry Fukuoka Cancer Registry Hiroshima Cancer Registry Hyogo Cancer Registry Kanagawa Cancer Registry Miyagi Prefectural Cancer Registry Nagasaki Prefectural Center Osaka Cancer Registry Saga Prefectural Cancer Registry Tottori Cancer Registry Yamagata Cancer Registry Malaysian Childhood Cancer Cancer Registry of Malaysia Registre du Cancer de Nouvelle New Zealand Cancer Registry Wasikato Tumour Registry
c/o Radiotherapy & Oncology Department Division of Epidemiology Fukui Medical Association Fukuoka Cancer Registry Radiation Effects Research Foundation (RERF) Hyogo Medical Center for Adults Kanagawa Cancer Center
GEN GEN GEN GEN GEN
POPU POPU POPU POPU POPU
HONG KONG JAPAN Aichi (Nagoya) JAPAN Fukui JAPAN Fukuoka JAPAN Hiroshima JAPAN Hyogo (Akashi) JAPAN Kanagawa (Yokohama) JAPAN Miyagi (Sendai) JAPAN Nagasaki JAPAN Osaka JAPAN Saga
GEN GEN
POPU POPU
GEN RERF Department of Field Research Department of Community Health Science Department of Hygiene Yamagata Center for Adults Malaysian Childhood Cancer Study Group Disease Control Unit 2nd Floor, Block E Institut Pasteur de Noumea NZ Health Information Service GEN GEN GEN
POPU POPU POPU POPU
GEN GEN CHIL GEN GEN GEN GEN
POPU POPU POPU POPU POPU POPU POPU
JAPAN Tottori (Yonago) JAPAN Yamagata MALAYSIA MALAYSIA Kuala Lumpur NEW CALEDONIA NEW ZEALAND NEW ZEALAND Wasikato
-297-
Manual on the prevention and control of common cancers
Papua New GuineaTumour Metro Cebu Population - Based Manila Cancer Registry DOH - Rizal Cancer Registry Central Cancer Registry Kangwha Cancer Registry Seoul Cancer Registry Singapore Cancer Registry Vanuatu Cancer Registry Registre du Cancer de Hanoi Ho Chi Minh City Cancer Registry
Hispathology Department Eduardo J. Aboitiz Cancer Center Philippine Cancer Society Rizal Medical Center
GEN GEN GEN GEN GEN
POPU POPU POPU POPU POPU POPU
PAPUA NEW GUINEA PHILIPPINES Cebu PHILIPPINES Manila PHILIPPINES Rizal KOREA (Republic of) KOREA (Republic of) Kangwha KOREA (Republic of) Seoul SINGAPORE VANUATU VIET NAM Hanoi VIET NAM Ho Chi Minh City
Department of Preventive Medicine and Public Department of Surgery
GEN
GEN
POPU
c/o Department of Pathology Ministry of Health Hopital Benh Vien K Institute of Oncology
GEN GEN GEN GEN
POPU POPU POPU POPU
-298-
Manual on the prevention and control of common cancers
Appendix 2 Antineoplastic and immunosuppressant drugs and drugs used in palliative care 1. Immunosuppressant drugs Route of administration, forms and strengths a tablet, 50 mg powder for injection, l00 mg (as sodium salt) in vial capsule, 25 mg concentrate for injection, 50 mg/ml in 1-ml ampoule
Drug dosage =azathioprine ciclosporin b
2.
Cytotoxic drugs Route of administration, forms and strengths a powder for injection, l0 000 IU in vial powder for injection, l5 mg (as sulfate) in vial tablet, 15 mg injection, 3 mg/ml in l0-ml ampoule powder for injection, l0 mg (hydrochloride) in vial powder for injection, l0 mg, 50 mg in vial tablet, 25 mg powder for injection, 500 mg in vial powder for injection, l00 mg in vial powder for injection, l00 mg in vial powder for injection, 500 mg in vial powder for injection, 10 mg, 50 mg (hydrochloride) in vial capsule, l00 mg injection, 20 mg/ml in 5-ml ampoule injection, 50 mg/ml in 5-ml ampoule tablet, 50 mg (as hydrochloride) tablet, 50 mg tablet, 2.5 mg (as sodium salt) powder for injection, 50 mg (as sodium salt) in vial capsule, 50 mg (as hydrochloride) powder for injection, l0 mg (sulfate) in vial powder for injection, l mg, 5 mg (sulfate) in vial
Drug asparaginase bleomycin calcium folinate chlormethine cisplatin cyclophosphamide cytarabine dacarbazine dactinomycin doxorubicin etoposide fluorouracil levamisole mercaptopurine methotrexate procarbazine vinblastine vincristine
-299-
Manual on the prevention and control of common cancers
3.
Hormones and antihormones Route of administration, forms and strengths a tablet, 5 mg powder for injection, 20 mg, 25 mg (as sodium phosphate or sodium succinate) in vial tablet, l0 mg, 20 mg (as citrate)
Drug =prednisolone tamoxifen a
b =
When the strength is specified in terms of a selected salt or ester, this is mentioned in brackets; when it refers to the active moiety, the name of the salt or ester in brackets is preceded by the word "as". For organ transplantation. Example of a therapeutic group.
Source: The Use of Essential Drugs. Sixth Report of the WHO Expert Commitee. Geneva, World Health Organization, 1995 (WHO Technical Report Series No. 850).
-300-
Manual on the prevention and control of common cancers
Appendix 3 Clinical staging of lung cancer
T - Primary Tumour TX Primary tumour cannot be assessed; tumour can be proven by the presence of malignant cells in sputum or bronchial washings but not visualized by imaging or bronchoscopy No evidence or primary tumour Carcinoma in situ Tumour ≤3 cm in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e. not in the main bronchus) Tumour with any of the following features of size or extent: >3 cm in greatest dimension Involves main bronchus ≥2 cm distal to the carina Invades visceral pleura Associated with atelectasis or obstructus pneumonitis, that extends to the hilar region but does not involve the entire lung T3 Tumour of any size that directly invades any of the following: chest wall (including superior sulcus tumours), diaphragm, mediastinal pleura, parietal paricardium; or tumour in the main bronchus <2 cm distal to the carina, but without involvement of the carina; or associated atelectasis or obstructive pneumonitis of the entire lung. Tumour of any size that invades any of the following: mediastinum, heart, great vessels, trachea, oesophagus, vertebral body, carina; or tumour with malignant pleural effusion.
TO Tis T1
T2
T4
N - Regional lymph nodes NX NO N1 Regional lymph nodes cannot be assessed No regional lymph node metastasis Metastasis to ipsilateral peribronchial and/or ipsilateral hilar lymph nodes, and intrapulmonary nodes including involvement by direct etension of the primary tumour. Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s)
N2
-301-
Manual on the prevention and control of common cancers
N3
Metastasis to contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s)
M - Distant Metastasis MX MO M1 Stage grouping Occult Carcinoma Stage 0 Stage IA Stage IB Stage IIA Stage IIB TX Tis T1 T2 T1 T2 T3 Stage IIIA T1 T2 T3 T3 Stage IIIB Any T T4 Stage IV Any T NO NO NO NO N1 N1 NO N2 N2 NI N2 N3 Any N Any N MO MO MO MO MO MO MO MO MO MO MO MO MO M1 Distant metastasis cannot be assessed No distant metastasis Distant metastasis
-302-
Manual on the prevention and control of common cancers
Appendix 4 Clinical staging of cervical cancer
Stage O Stage 1
Carcinoma in situ The carcinoma is strictly confined to the cervix (extension to the corpus is disregarded). Stage Ia Microinvasive disease with lesion not grossly visible (All gross lesions, even if with superficial invasion, are staged as Ib) The depth of invasion should not be more than 5 mm from the base of the epithelium, either surface or glandular, from which it originates. Vascular space involvement, either venous or lymphatic, should not alter the staging. Stage Ia1 The depth of stromal invasion should not exceed 3 mm and the horizontal diameter should not exceed 7 mm The depth of stromal invasion is greater than 3 mm but should not exceed 5 mm and the horizontal diameter should not exceed 7 mm.
Stage Ia2
Stage Ib
Clinical lesions confined to the cervix or preclinical lesions greater than Ia Stage Ib1 Stage Ib2 Clinical lesions not greater than 4 cm in diameter Clinical lesions greater than 4 cm in diameter
Stage II
The carcinoma extends beyond the cervix, to the parametria, but has not reached the pelvic wall. The carcinoma extends to the vagina, but has not reached the lower third. Stage IIa Stage IIb Without obvious parametrial involvement. With obvious parametrial involvement.
Stage III
The carcinoma extends to the pelvic wall. On rectal examination, there is no cancer-free space between the tumour and the pelvic wall. The tumour involves the lower third of the vagina. All cases with hydronephrosis or nonfunctioning kidney are included, unless they are known to be due to some other cause. Stage IIIa Stage IIIb Without extension to the pelvic wall. With extension to the pelvic wall and/or hydronephrosis or nonfunctioning kidney.
-303-
Manual on the prevention and control of common cancers
Stage IV
The carcinoma extends beyond the true pelvis or clinically involves the mucose of the bladder or the rectum. A bullous oedema as such does permit a case to be alloted to Stage IV. Stage IVa Stage IVb Spread to adjacent organs Spread to distant organs.
Stage Grouping Stage O Stage 1A1 Stage 1A2 Stage 1B1 Stage 1B2 Stage IIA Stage IIB Stage IIIA Stage IIIB Tis T1a1 T1a2 T1b1 T1b2 T2a T2b T3a T1 T2 T3a T3b Stage IVA Stage IVB T4 Any T NO NO NO NO NO NO NO NO N1 N1 N1 Any N Any N Any N MO MO MO MO MO MO MO MO MO MO MO MO MO M1
-304-
Manual on the prevention and control of common cancers
Appendix 5 Clinical staging of oral cancer Definition of TNM Primary Tumour (T) TX TO Tis T1 T2 T3 T4 (lip) Primary tumour cannot be assessed No evidence of primary tumour Carcinoma in situ Tumour 2 cm or less in greatest dimension Tumour more than 2 cm but not more than 4 cm in greatest dimension Tumour more than 4 cm in greatest dimension Tumour invades adjacent structures (e.g. through cortical bone,inferior alveolar nerve, floor of mouth, skin of face) Tumour invades adjacent structures (e.g. through cortical bone, into deep (extrinsic) muscle of tongue, maxillary sinus, skin. Superficial erosion alone of bone/tooth socket by gingival primary is not sufficient to classify as T4)
T4 (Oral cavity)
Regional Lymph Nodes
(N) NX NO N1 N2 Regional lymph nodes cannot be assessed No regional lymph node metastasis Metastasis in a single ipsilateral lymph node, more than 3 cm or less in greatest dimension Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension; or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension N2a Metastasis in single ipsilateral lymph node more than 3 cm but not more than 6 cm in greatest dimension Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension
N2b
-305-
Manual on the prevention and control of common cancers
N2c
Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension
N3 Distant Metastasis (M) MX MO M1 Stage Grouping Stage 0 Stage I Stage II Stage III Tis T1 T2 T3 T1 T2 T3 Stage IVA T4 T4 Any T Stage IVB Stage IVC Any T Any T
Metastasis in a lymph node more than 6 cm in greatest dimension
Distant metastasis cannot be assesed No distant metastasis Distant metastasis
NO NO NO NO N1 N1 N1 NO N1 N2 N3 Any N
MO MO MO MO MO MO MO MO MO MO MO M1
-306-
Manual on the prevention and control of common cancers
Appendix 6 Clinical staging of liver cancer Definition of TNM Primary Tumour (T) TX TO T1 T2 Primary tumour cannot be assessed No evidence of primary tumour Solitary tumour 2 cm or less in greatest dimension without vascular invasion Solitary tumour 2 cm or less in greatest dimension with vascular invasion, or multiple tumours limited to one lobe, none more than, 2 cm in greatest dimension without vascular invasion, or a solitary tumour more than 2 cm in greatest dimension without vascular invasion Solitary tumour more than 2 cm in greatest dimension with vascular invasion, or multiple tumours limited to one lobe, none more than 2 cm in greatest dimension with vascular invasion, or multiple tumours limited to one lobe, any more than 2 cm in greatest dimension, with or without vascular invasion Multiple tumours in more than one lobe or tumour(s) involve(s) a major branch of portal or hepatic vein (s) or invasion of adjacent organs other than the gallbladder or perforation of the visceral peritoneum
T3
T4
Regional Lymph Nodes
(N) NX NO N1 Regional lymph nodes cannot be assessed No regional lymph node metastasis Regional lymph node metastasis
Distant Metastasis
(M) MX MO M1 Presence of distant metastasis cannot be assessed No distant metastasis Distant metastasis
-307-
Manual on the prevention and control of common cancers
Stage Grouping Stage 1 Stage II Stage IIIA Stage IIIB T1 T2 T3 T1 T2 T3 Stage IVA Stage IVB T4 Any T NO NO NO N1 N1 NI Any N Any N MO MO MO MO MO MO MO M1
-308-
Manual on the prevention and control of common cancers
Appendix 7 Clinical staging of breast cancer Definition of TNM Definitions for classifying the primary tumour (T) are the same for clinical and for pathologic classification. The telescoping method of classification can be applied. If the measurement is made by physical examination, the examiner will use the major headings (T1, T2, or T3). If other measurements, such as mammographic or pathologic, are used, the telescoped subsets of T1 can be used. Primary Tumour (T) TX TO Tis* Primary tumour cannot be assessed No evidence of primary tumour Carcinoma in situ: intraductal carcinoma, lobular carcinoma in situ, or Paget’s disease of the nipple without tumour. Tumour 2 cm or less in greatest dimension T1mic T1a T1b T1c T2 T3 T4+ Microinvasion 0.1 cm or less in greatest dimension More than 0.1 but not more than 0.5 cm in greatest dimension More than 0.5 cm but not more than 1 cm in greatest dimension More than 1 cm but not more than 2 cm in greatest dimension
T1
Tumour more than 2 cm but not more than 5 cm in greatest dimension Tumour more than 5 cm in greatest dimension Tumour of any size with direct extension to (a) chest wall or (b) skin, only as described below. T4a T4b Extension to chest wall Edema (including peau d’orange) or ulceration of the skin of the breast or satellite skin nodules confined to the same breast Both (T4a and T4b) Inflammatory carcinoma
T4c T4d
*Note: Paget’s disease associated with a tumour is classified according to the size of the tumour.
-309-
Manual on the prevention and control of common cancers
+Note: Chest wall includes ribs, intercostal muscles, and serratus anterior muscle but not pectoral muscle. Regional Lymph Nodes (N) NX NO N1 N2 N3 Pathologic Classification (pN) pNx pNO pN1 Regional lymph nodes cannot be assessed (e,g, previously removed or not removed for pathologic study) No regional lymph node metastasis Metastasis to movable ipsilateral axillary lymph node(s) pN1a pN1b Only micrometastasis (none larger than 0.2 cm) Metastasis to lymph node(s), any larger than 0.2 cm pN1bi Metastasis in 1 to 3 lymph nodes, any more than 0.2 cm and all less than 2 cm in greatest dimension Metastasis to 4 or more lymph nodes, any more than 0.2 cm in greatest dimension Extension of tumour beyond the capsule of a lymph node metastasis less than 2 cm in greatest dimension Metastasis to a lymph node 2 cm or more in greatest dimension Regional lymph nodes cannot be assessed (e.g. previously removed) No regional lymph node metastasis Metastasis to movable ipsilateral axillary lymph node (s) Metastasis to ipsilateral axillary lymph node(s) fixed to one another or to other structures Metastasis to ipsilateral internal mammary lymph node(s)
pN1bii
pN1biii
pN1biv pN2 pN3 Distant Metastasis (M) MX
Metastasis to ipsilateral axillary lymph nodes that are fixed to one another or to other structures Metastasis to ipsilateral internal mammary lymph node(s)
Distant metastasis cannot be assessed
-310-
Manual on the prevention and control of common cancers
MO M1
No distant metastasis Distant metastasis (includes metastasis to ipsilateral supraclavicular lymph node[s])
Stage grouping Stage O Stage I Stage IIA Tis T1* TO T1* T2 Stage IIB T2 T3 Stage IIIA TO T1* T2 T3 Stage IIIB T4 Any T Stage IV Any T NO NO N1 N1** NO N1 NO N2 N2 N2 N1, N2 Any N N3 Any N MO MO MO MO MO MO MO MO MO MO MO MO MO M1
*Note: T1 includes T1mic **Note: The prognosis of patients with pN1a is similar to that of patients with pNO.
-311-
Manual on the prevention and control of common cancers
Appendix 8 Clinical staging of stomach cancer Definition of TNM Primary Tumour (T) TX TO Tis T1 T2 T3 Primary tumour cannot be assessed No evidence of primary tumour Carcinoma in situ: intraepithelial tumour without invasion of the lamina propria Tumour invades the lamina propria or submucosa Tumour invades the muscularis propria of the subserosa* Tumour penetrates the serosa (visceral peritoneum) without invasion of adjacent structures + Tumour invades adjacent structures ++
T4
*Note: A tumour may penetrate the muscularis propria with extension into the gastrocolic or gastrohepatic ligaments or into the greater of lesser omentum without perforation of the visceral peritoneum covering these structures. In this case, the tumour is classified T2. If there is perforation of the visceral perinoneum covering the gastric ligaments or omentum, the tumour should be classified T3. +
The adjacent structures of the stomach are the spleen, transverse colon, liver, diaphragm, pancreas, abdominal wall, adrenal gland, kidney, small intestine, and retroperitoneum. ++
Intramural extension to the doudenum or esophagus is classified by the depth of greatest invasion in any of these sites, including stomach. Regional Lymph Nodes (N) NX NO N1 N2 N3 Distant Metastasis (M) MX MO Distant metastasis cannot be assessed No distant metastasis Regional lymph node(s) cannot be assessed No regional lymph node metastasis Metastasis in 1 to 6 regional lymph nodes Metastasis in 7 to 15 regional lymph nodes Metastasis in more than 15 regional lymph nodes
-312-
Manual on the prevention and control of common cancers
M1
Distant metastasis
Stage grouping Stage 0 Stage IA Stage 1B Tis T1 T1 T2 Stage II T1 T2 T3 Stage IIIA T2 T3 T4 Stage IIIB Stage IV T3 T4 T1 T2 T3 T4 T4 Any T NO NO N1 NO N2 N1 NO N2 N1 NO N2 N1 N3 N3 N3 N2 N3 Any N MO MO MO MO MO MO MO MO MO MO MO MO MO MO MO MO MO M1
-313-
Manual on the prevention and control of common cancers
Appendix 9 Clinical staging of colonic and rectal cancer Definition of TNM The same classification is used for both clinical and pathologic staging. Primary Tumour (T) TX TO Tis T1 T2 T3 Primary tumour cannot be assessed No evidence of primary tumour Carcinoma in situ: intraepithelial or invasion of lamina propria* Tumour invades submucosa Tumour invades muscularis propria Tumour invades through the muscularis propria into the subserosa, or into nonperitonealized pericolic or perirectal tissues Tumour perforates the visceral peritoneum, or directly invades other organs or structures.**
T4
*Note: Tis includes cancer cells confined within the glandular basement membrane (intraepithelial) or lamina propria (intramucosal) with no extension through the muscularis mucosae into the submucosa. **Note: Direct invasion in T4 includes invasion of other segments of the colorectum by way of the serosa’ for example, invasion of the sigmoid colon by a carcinoma of the cecum. Regional Lymph Nodes (N) NX NO N1 N2 Distant Metastasis (M) MX MO M1 Presence of distant metastasis cannot be assessed No distant metastasis Distant metastasis Regional lymph nodes cannot be assessed No regional lymph node metastasis Metastasis in 1 to 3 regional lymph nodes Metastasis in 4 or more regional lymph nodes
-314-
Manual on the prevention and control of common cancers
Stage Grouping AJCC/UICC Stage O Stage 1 Tis T1 T2 Stage II T3 T4 Stage III Any T Any T Stage IV Any T NO NO NO NO NO N1 N2 Any N MO MO MO MO MO MO MO M1 Dukes* A B C -
* Dukes B is a composite of better (T3, NO, MO) and worse (T4, NO, MO) prognostic groups as is Dukes C (Any T, N1, MO) and (Any T, N2, MO)
-315-
Manual on the prevention and control of common cancers
Appendix 10 Clinical staging of oesophageal cancer Definition of TNM Primary Tumour (T) TX TO Tis Ti T2 T3 T4 Regional Lymph Nodes (N) NX NO N1 Distant metastasis (M) MX MO M1 Distant metastasis cannot be assessed No distant metastasis Distant metastasis Regional lymph nodes cannot be assessed No regional lymph node metastasis Regional lymph node metastasis Primary tumour cannot be assessed No evidence of primary tumour Carcinoma in situ Tumour invades lamina propria or submucosa Tumour invades muscularis propria Tumour invades adventitia Tumour invades adjacent structures
Tumours of the lower thoracic oesophagus: M1a M1b Metastasis in celiac lymph nodes Other distant metastasis
Tumours of the midthoracic oesophagus M1a M1b Not applicable Nonregional lymph nodes and/or other distant metastasis
Tumours of the upper thoracic oesophagus M1a M1b Metastasis in cervical nodes Other distant metastasis
-316-
Manual on the prevention and control of common cancers
Stage Grouping Stage O Stage I Stage IIA Tis T1 T2 T3 Stage IIB T1 T2 Stage III T3 T4 Stage IV Stage IVA Stage IVB Any T Any T Any T NO NO NO NO N1 N1 N1 Any N Any N Any N Any N MO MO MO MO MO MO MO MO M1 M1a M1b
-317-
Manual on the prevention and control of common cancers
Appendix 11 Clinical staging of nasopharyngeal cancer Definition of TNM Primary Tumour (T) TX TO Tis TI T2 Primary tumour cannot be assessed No evidence of primary tumour Carcinoma in situ Tumour confined to nasopharynx Tumour extends to soft tissues of oropharynx and/or nasal fossa T2a T2b T3 T4 without parapharyngeal extension with parapharyngeal extension
Tumour invadesbony structures and/or paanasal sinuses Tumourwith intracranial extension and/or involvement of cranial nerves, infratemporal fossa, hybopharynx, or orbit
Regional Lymph Nodes
(N) NX NO N1 Regional lymph nodes cannot be assessed No regional lymph node metastasis Unilateral metastasis in lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossa Bilateral metastasis in lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossa Metastasis in a lymph node(s) N3a N3b N2c greater rhan 6 cm in dimension extension to the supraclavicular fossa Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greater dimension.
N2
N3
-318-
Manual on the prevention and control of common cancers
Distant Metastasis
(M) MX MO MI Presence of distant metastasis cannot be assessed No distant metastasis Distant metastasis
Stage grouping Stage O Stage I Stage IIA Stage IIB Tis T1 T2a T1 T2 T2a T2b T2b Stage III T1 T2a T2b T3 T3 Stage IVA T4 T4 T4 Stage IVB Stage IVC Any T Any T NO NO NO N1 N1 N1 NO N1 N2 N2 N2 NO N2 NO N1 N2 N3 Any N MO MO MO MO MO MO MO MO MO MO MO MO MO MO MO MO MO M1
-319-
Appendices: Appendix 1: Appendix 2: Appendix 3: Appendix 4: Appendix 5: Appendix 6: Appendix 7: Appendix 8: Appendix 9: Appendix 10: Appendix 11: Population - based cancer registries which are members of the International Association of Cancer Registries Antineoplastic and immunosuppressant drugs and drugs used in palliative care Clinical staging of oral cancer Clinical staging of nasopharyngeal cancer Clinical staging of oesophageal cancer Clinical staging of stomach cancer Clinical staging of colonic and rectal cancer Clinical staging of liver cancer Clinical staging of lung cancer Clinical staging of breast cancer Clinical staging of cervical cancer
Manual on the prevention and control of common cancers
Appendix 1 Population - based cancer registries which are members of the International Association of Cancer Registries Name Australian Paediatric Cancer ACT Cancer Registry Northern Territory Cancer Registry Queensland Cancer Registry South Australian Cancer Registry Tasmanian Cancer Registry Victoria Cancer Registry Western Australia Cancer Registry Beijing Cancer Registry Qidong Cancer Registry Shanghai Cancer Registry Tianjin Cancer Registry Zhongshan Cancer Registry Fiji Cancer Registry Registre du Cancer Hong Kong Cancer Registry Aichi Cancer Registry Fukui Cancer Registry Fukuoka Cancer Registry Hiroshima Cancer Registry Hyogo Cancer Registry Kanagawa Cancer Registry Miyagi Prefectural Cancer Registry Nagasaki Prefectural Cancer Registry Osaka Cancer Registry Saga Prefectural Cancer Registry Population CHIL GEN GEN GEN GEN GEN GEN GEN GEN GEN GEN GEN GEN GEN GEN GEN GEN GEN GEN GEN GEN GEN GEN GEN GEN GEN AUSTRALIA AUSTRALIA ACT AUSTRALIA Northern Territory AUSTRALIA Queensland AUSTRALIA South Australia AUSTRALIA Tasmania AUSTRALIA Victoria AUSTRALIA Western Australia CHINA Beijing CHINA Qidong CHINA Shanghai CHINA Tianjin CHINA Zhongshan City FIJI FRENCH POLYNESIA HONG KONG JAPAN Aichi (Nagoya) JAPAN Fukui JAPAN Fukuoka JAPAN Hiroshima JAPAN Hyogo (Akashi) JAPAN Kanagawa (Yokohama) JAPAN Miyagi (Sendai) JAPAN Nagasaki JAPAN Osaka JAPAN Saga Place
-296-
Manual on the prevention and control of common cancers
Tottori Cancer Registry Yamagata Cancer Registry Malaysian Childhood Cancer Registry Cancer Registry of Malaysia Registre du Cancer de Nouvelle New Zealand Cancer Registry Wasikato Tumour Registry Papua New GuineaTumour Registry Metro Cebu Cancer Registry Population - Based Manila Cancer Registry Department of Health - Rizal Cancer Registry Central Cancer Registry Kangwha Cancer Registry Seoul Cancer Registry Singapore Cancer Registry Vanuatu Cancer Registry Registre du Cancer de Hanoi Ho Chi Minh City Cancer Registry CHIL= Children GEN = General
GEN GEN CHIL GEN GEN GEN GEN GEN GEN GEN GEN GEN GEN GEN GEN GEN GEN GEN
JAPAN Tottori (Yonago) JAPAN Yamagata MALAYSIA MALAYSIA Kuala Lumpur NEW CALEDONIA NEW ZEALAND NEW ZEALAND Wasikato PAPUA NEW GUINEA PHILIPPINES Cebu PHILIPPINES Manila PHILIPPINES Rizal KOREA (Republic of) KOREA (Republic of) Kangwha KOREA (Republic of) Seoul SINGAPORE VANUATU VIET NAM Hanoi VIET NAM Ho Chi Minh City
-297-
Manual on the prevention and control of common cancers
Appendix 2 Antineoplastic and immunosuppressant drugs and drugs used in palliative care 1. Immunosuppressant drugs Route of administration, forms and strengths a tablet, 50 mg powder for injection, l00 mg (as sodium salt) in vial capsule, 25 mg concentrate for injection, 50 mg/ml in 1-ml ampoule
Drug dosage =azathioprine ciclosporin b
2.
Cytotoxic drugs Route of administration, forms and strengths a powder for injection, 10 000 IU in vial powder for injection, 15 mg (as sulfate) in vial tablet, 15 mg injection, 3 mg/ml in 10-ml ampoule powder for injection, 10 mg (hydrochloride) in vial powder for injection, 10 mg, 50 mg in vial tablet, 25 mg powder for injection, 500 mg in vial powder for injection, 100 mg in vial powder for injection, 100 mg in vial powder for injection, 500 mg in vial powder for injection, 10 mg, 50 mg (hydrochloride) in vial capsule, 100 mg injection, 20 mg/ml in 5-ml ampoule injection, 50 mg/ml in 5-ml ampoule tablet, 50 mg (as hydrochloride) tablet, 50 mg tablet, 2.5 mg (as sodium salt) powder for injection, 50 mg (as sodium salt) in vial capsule, 50 mg (as hydrochloride) powder for injection, 10 mg (sulfate) in vial powder for injection, 1 mg, 5 mg (sulfate) in vial
Drug asparaginase bleomycin calcium folinate chlormethine cisplatin cyclophosphamide cytarabine dacarbazine dactinomycin doxorubicin etoposide fluorouracil levamisole mercaptopurine methotrexate procarbazine vinblastine vincristine
-298-
Manual on the prevention and control of common cancers
3.
Hormones and antihormones Route of administration, forms and strengths a tablet, 5 mg powder for injection, 20 mg, 25 mg (as sodium phosphate or sodium succinate) in vial tablet, l0 mg, 20 mg (as citrate)
Drug =prednisolone tamoxifen a
b =
When the strength is specified in terms of a selected salt or ester, this is mentioned in brackets; when it refers to the active moiety, the name of the salt or ester in brackets is preceded by the word "as". For organ transplantation. Example of a therapeutic group.
Source: The Use of Essential Drugs. Sixth Report of the WHO Expert Committee. Geneva, World Health Organization, 1995 (WHO Technical Report Series No. 850).
-299-
Manual on the prevention and control of common cancers
Appendix 3 Clinical staging of oral cancer Definition of TNM Primary Tumour (T) TX TO Tis T1 T2 T3 T4 (lip) Primary tumour cannot be assessed No evidence of primary tumour Carcinoma in situ Tumour 2 cm or less in greatest dimension Tumour more than 2 cm but not more than 4 cm in greatest dimension Tumour more than 4 cm in greatest dimension Tumour invades adjacent structures (e.g. through cortical bone,inferior alveolar nerve, floor of mouth, skin of face) Tumour invades adjacent structures (e.g. through cortical bone, into deep (extrinsic) muscle of tongue, maxillary sinus, skin. Superficial erosion alone of bone/tooth socket by gingival primary is not sufficient to classify as T4)
T4 (Oral cavity)
Regional Lymph Nodes
(N) NX NO N1 N2 Regional lymph nodes cannot be assessed No regional lymph node metastasis Metastasis in a single ipsilateral lymph node, more than 3 cm or less in greatest dimension Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension; or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension N2a Metastasis in single ipsilateral lymph node more than 3 cm but not more than 6 cm in greatest dimension Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension
N2b
-300-
Manual on the prevention and control of common cancers
N2c
Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension
N3 Distant Metastasis (M) MX MO M1 Stage Grouping Stage 0 Stage I Stage II Stage III Tis T1 T2 T3 T1 T2 T3 Stage IVA T4 T4 Any T Stage IVB Stage IVC Any T Any T
Metastasis in a lymph node more than 6 cm in greatest dimension
Distant metastasis cannot be assesed No distant metastasis Distant metastasis
NO NO NO NO N1 N1 N1 NO N1 N2 N3 Any N
MO MO MO MO MO MO MO MO MO MO MO M1
-301-
Manual on the prevention and control of common cancers
Appendix 4 Clinical staging of nasopharyngeal cancer Definition of TNM Primary Tumour (T) TX TO Tis TI T2 Primary tumour cannot be assessed No evidence of primary tumour Carcinoma in situ Tumour confined to nasopharynx Tumour extends to soft tissues of oropharynx and/or nasal fossa T2a T2b T3 T4 without parapharyngeal extension with parapharyngeal extension
Tumour invadesbony structures and/or paanasal sinuses Tumourwith intracranial extension and/or involvement of cranial nerves, infratemporal fossa, hybopharynx, or orbit
Regional Lymph Nodes
(N) NX NO N1 Regional lymph nodes cannot be assessed No regional lymph node metastasis Unilateral metastasis in lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossa Bilateral metastasis in lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossa Metastasis in a lymph node(s) N3a N3b N2c greater rhan 6 cm in dimension extension to the supraclavicular fossa Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greater dimension.
N2
N3
-302-
Manual on the prevention and control of common cancers
Distant Metastasis
(M) MX MO MI Presence of distant metastasis cannot be assessed No distant metastasis Distant metastasis
Stage grouping Stage O Stage I Stage IIA Stage IIB Tis T1 T2a T1 T2 T2a T2b T2b Stage III T1 T2a T2b T3 T3 Stage IVA T4 T4 T4 Stage IVB Stage IVC Any T Any T NO NO NO N1 N1 N1 NO N1 N2 N2 N2 NO N2 NO N1 N2 N3 Any N MO MO MO MO MO MO MO MO MO MO MO MO MO MO MO MO MO M1
-303-
Manual on the prevention and control of common cancers
Appendix 5 Clinical staging of oesophageal cancer Definition of TNM Primary Tumour (T) TX TO Tis Ti T2 T3 T4 Regional Lymph Nodes (N) NX NO N1 Distant metastasis (M) MX MO M1 Distant metastasis cannot be assessed No distant metastasis Distant metastasis Regional lymph nodes cannot be assessed No regional lymph node metastasis Regional lymph node metastasis Primary tumour cannot be assessed No evidence of primary tumour Carcinoma in situ Tumour invades lamina propria or submucosa Tumour invades muscularis propria Tumour invades adventitia Tumour invades adjacent structures
Tumours of the lower thoracic oesophagus: M1a M1b Metastasis in celiac lymph nodes Other distant metastasis
Tumours of the midthoracic oesophagus M1a M1b Not applicable Nonregional lymph nodes and/or other distant metastasis
Tumours of the upper thoracic oesophagus M1a M1b Metastasis in cervical nodes Other distant metastasis
-304-
Manual on the prevention and control of common cancers
Stage Grouping Stage O Stage I Stage IIA Tis T1 T2 T3 Stage IIB T1 T2 Stage III T3 T4 Stage IV Stage IVA Stage IVB Any T Any T Any T NO NO NO NO N1 N1 N1 Any N Any N Any N Any N MO MO MO MO MO MO MO MO M1 M1a M1b
-305-
Manual on the prevention and control of common cancers
Appendix 6 Clinical staging of stomach cancer Definition of TNM Primary Tumour (T) TX TO Tis T1 T2 T3 Primary tumour cannot be assessed No evidence of primary tumour Carcinoma in situ: intraepithelial tumour without invasion of the lamina propria Tumour invades the lamina propria or submucosa Tumour invades the muscularis propria of the subserosa* Tumour penetrates the serosa (visceral peritoneum) without invasion of adjacent structures + Tumour invades adjacent structures ++
T4
*Note: A tumour may penetrate the muscularis propria with extension into the gastrocolic or gastrohepatic ligaments or into the greater of lesser omentum without perforation of the visceral peritoneum covering these structures. In this case, the tumour is classified T2. If there is perforation of the visceral perinoneum covering the gastric ligaments or omentum, the tumour should be classified T3. +
The adjacent structures of the stomach are the spleen, transverse colon, liver, diaphragm, pancreas, abdominal wall, adrenal gland, kidney, small intestine, and retroperitoneum. ++
Intramural extension to the doudenum or esophagus is classified by the depth of greatest invasion in any of these sites, including stomach. Regional Lymph Nodes (N) NX NO N1 N2 N3 Distant Metastasis (M) MX MO Distant metastasis cannot be assessed No distant metastasis Regional lymph node(s) cannot be assessed No regional lymph node metastasis Metastasis in 1 to 6 regional lymph nodes Metastasis in 7 to 15 regional lymph nodes Metastasis in more than 15 regional lymph nodes
-306-
Manual on the prevention and control of common cancers
M1
Distant metastasis
Stage grouping Stage 0 Stage IA Stage 1B Tis T1 T1 T2 Stage II T1 T2 T3 Stage IIIA T2 T3 T4 Stage IIIB Stage IV T3 T4 T1 T2 T3 T4 T4 Any T NO NO N1 NO N2 N1 NO N2 N1 NO N2 N1 N3 N3 N3 N2 N3 Any N MO MO MO MO MO MO MO MO MO MO MO MO MO MO MO MO MO M1
-307-
Manual on the prevention and control of common cancers
Appendix 7 Clinical staging of colonic and rectal cancer Definition of TNM The same classification is used for both clinical and pathologic staging. Primary Tumour (T) TX TO Tis T1 T2 T3 Primary tumour cannot be assessed No evidence of primary tumour Carcinoma in situ: intraepithelial or invasion of lamina propria* Tumour invades submucosa Tumour invades muscularis propria Tumour invades through the muscularis propria into the subserosa, or into nonperitonealized pericolic or perirectal tissues Tumour perforates the visceral peritoneum, or directly invades other organs or structures.**
T4
*Note: Tis includes cancer cells confined within the glandular basement membrane (intraepithelial) or lamina propria (intramucosal) with no extension through the muscularis mucosae into the submucosa. **Note: Direct invasion in T4 includes invasion of other segments of the colorectum by way of the serosa’ for example, invasion of the sigmoid colon by a carcinoma of the cecum. Regional Lymph Nodes (N) NX NO N1 N2 Distant Metastasis (M) MX MO M1 Presence of distant metastasis cannot be assessed No distant metastasis Distant metastasis Regional lymph nodes cannot be assessed No regional lymph node metastasis Metastasis in 1 to 3 regional lymph nodes Metastasis in 4 or more regional lymph nodes
-308-
Manual on the prevention and control of common cancers
Stage Grouping AJCC/UICC Stage O Stage I Tis T1 T2 Stage II T3 T4 Stage III Any T Any T Stage IV Any T NO NO NO NO NO N1 N2 Any N MO MO MO MO MO MO MO M1 Dukes* A B C -
* Dukes B is a composite of better (T3, NO, MO) and worse (T4, NO, MO) prognostic groups as is Dukes C (Any T, N1, MO) and (Any T, N2, MO)
-309-
Manual on the prevention and control of common cancers
Appendix 8 Clinical staging of liver cancer Definition of TNM Primary Tumour (T) TX TO T1 T2 Primary tumour cannot be assessed No evidence of primary tumour Solitary tumour 2 cm or less in greatest dimension without vascular invasion Solitary tumour 2 cm or less in greatest dimension with vascular invasion, or multiple tumours limited to one lobe, none more than, 2 cm in greatest dimension without vascular invasion, or a solitary tumour more than 2 cm in greatest dimension without vascular invasion Solitary tumour more than 2 cm in greatest dimension with vascular invasion, or multiple tumours limited to one lobe, none more than 2 cm in greatest dimension with vascular invasion, or multiple tumours limited to one lobe, any more than 2 cm in greatest dimension, with or without vascular invasion Multiple tumours in more than one lobe or tumour(s) involve(s) a major branch of portal or hepatic vein (s) or invasion of adjacent organs other than the gallbladder or perforation of the visceral peritoneum
T3
T4
Regional Lymph Nodes
(N) NX NO N1 Regional lymph nodes cannot be assessed No regional lymph node metastasis Regional lymph node metastasis
Distant Metastasis
(M) MX MO M1 Presence of distant metastasis cannot be assessed No distant metastasis Distant metastasis
-310-
Manual on the prevention and control of common cancers
Stage Grouping Stage 1 Stage II Stage IIIA Stage IIIB T1 T2 T3 T1 T2 T3 Stage IVA Stage IVB T4 Any T NO NO NO N1 N1 NI Any N Any N MO MO MO MO MO MO MO M1
-311-
Manual on the prevention and control of common cancers
Appendix 9 Clinical staging of lung cancer
T - Primary Tumour TX Primary tumour cannot be assessed; tumour can be proven by the presence of malignant cells in sputum or bronchial washings but not visualized by imaging or bronchoscopy No evidence or primary tumour Carcinoma in situ Tumour ≤3 cm in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e. not in the main bronchus) Tumour with any of the following features of size or extent: >3 cm in greatest dimension Involves main bronchus ≥2 cm distal to the carina Invades visceral pleura Associated with atelectasis or obstructus pneumonitis, that extends to the hilar region but does not involve the entire lung T3 Tumour of any size that directly invades any of the following: chest wall (including superior sulcus tumours), diaphragm, mediastinal pleura, parietal paricardium; or tumour in the main bronchus <2 cm distal to the carina, but without involvement of the carina; or associated atelectasis or obstructive pneumonitis of the entire lung. Tumour of any size that invades any of the following: mediastinum, heart, great vessels, trachea, oesophagus, vertebral body, carina; or tumour with malignant pleural effusion.
TO Tis T1
T2
T4
N - Regional lymph nodes NX NO N1 Regional lymph nodes cannot be assessed No regional lymph node metastasis Metastasis to ipsilateral peribronchial and/or ipsilateral hilar lymph nodes, and intrapulmonary nodes including involvement by direct etension of the primary tumour. Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s)
N2
-312-
Manual on the prevention and control of common cancers
N3
Metastasis to contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s)
M - Distant Metastasis MX MO M1 Stage grouping Occult Carcinoma Stage 0 Stage IA Stage IB Stage IIA Stage IIB TX Tis T1 T2 T1 T2 T3 Stage IIIA T1 T2 T3 T3 Stage IIIB Any T T4 Stage IV Any T NO NO NO NO N1 N1 NO N2 N2 NI N2 N3 Any N Any N MO MO MO MO MO MO MO MO MO MO MO MO MO M1 Distant metastasis cannot be assessed No distant metastasis Distant metastasis
-313-
Manual on the prevention and control of common cancers
Appendix 10 Clinical staging of breast cancer Definition of TNM Definitions for classifying the primary tumour (T) are the same for clinical and for pathologic classification. The telescoping method of classification can be applied. If the measurement is made by physical examination, the examiner will use the major headings (T1, T2, or T3). If other measurements, such as mammographic or pathologic, are used, the telescoped subsets of T1 can be used. Primary Tumour (T) TX TO Tis* Primary tumour cannot be assessed No evidence of primary tumour Carcinoma in situ: intraductal carcinoma, lobular carcinoma in situ, or Paget’s disease of the nipple without tumour. Tumour 2 cm or less in greatest dimension T1mic T1a T1b T1c T2 T3 T4+ Microinvasion 0.1 cm or less in greatest dimension More than 0.1 but not more than 0.5 cm in greatest dimension More than 0.5 cm but not more than 1 cm in greatest dimension More than 1 cm but not more than 2 cm in greatest dimension
T1
Tumour more than 2 cm but not more than 5 cm in greatest dimension Tumour more than 5 cm in greatest dimension Tumour of any size with direct extension to (a) chest wall or (b) skin, only as described below. T4a T4b Extension to chest wall Edema (including peau d’orange) or ulceration of the skin of the breast or satellite skin nodules confined to the same breast Both (T4a and T4b) Inflammatory carcinoma
T4c T4d
*Note: Paget’s disease associated with a tumour is classified according to the size of the tumour.
-314-
Manual on the prevention and control of common cancers
+Note: Chest wall includes ribs, intercostal muscles, and serratus anterior muscle but not pectoral muscle. Regional Lymph Nodes (N) NX NO N1 N2 N3 Pathologic Classification (pN) pNx pNO pN1 Regional lymph nodes cannot be assessed (e,g, previously removed or not removed for pathologic study) No regional lymph node metastasis Metastasis to movable ipsilateral axillary lymph node(s) pN1a pN1b Only micrometastasis (none larger than 0.2 cm) Metastasis to lymph node(s), any larger than 0.2 cm pN1bi Metastasis in 1 to 3 lymph nodes, any more than 0.2 cm and all less than 2 cm in greatest dimension Metastasis to 4 or more lymph nodes, any more than 0.2 cm in greatest dimension Extension of tumour beyond the capsule of a lymph node metastasis less than 2 cm in greatest dimension Metastasis to a lymph node 2 cm or more in greatest dimension Regional lymph nodes cannot be assessed (e.g. previously removed) No regional lymph node metastasis Metastasis to movable ipsilateral axillary lymph node (s) Metastasis to ipsilateral axillary lymph node(s) fixed to one another or to other structures Metastasis to ipsilateral internal mammary lymph node(s)
pN1bii
pN1biii
pN1biv pN2 pN3 Distant Metastasis (M) MX
Metastasis to ipsilateral axillary lymph nodes that are fixed to one another or to other structures Metastasis to ipsilateral internal mammary lymph node(s)
Distant metastasis cannot be assessed
-315-
Manual on the prevention and control of common cancers
MO M1
No distant metastasis Distant metastasis (includes metastasis to ipsilateral supraclavicular lymph node[s])
Stage grouping Stage O Stage I Stage IIA Tis T1* TO T1* T2 Stage IIB T2 T3 Stage IIIA TO T1* T2 T3 Stage IIIB T4 Any T Stage IV Any T NO NO N1 N1** NO N1 NO N2 N2 N2 N1, N2 Any N N3 Any N MO MO MO MO MO MO MO MO MO MO MO MO MO M1
*Note: T1 includes T1mic **Note: The prognosis of patients with pN1a is similar to that of patients with pNO.
-316-
Manual on the prevention and control of common cancers
Appendix 11 Clinical staging of cervical cancer
Stage O Stage 1
Carcinoma in situ The carcinoma is strictly confined to the cervix (extension to the corpus is disregarded). Stage 1a Microinvasive disease with lesion not grossly visible (All gross lesions, even if with superficial invasion, are staged as Ib) The depth of invasion should not be more than 5 mm from the base of the epithelium, either surface or glandular, from which it originates. Vascular space involvement, either venous or lymphatic, should not alter the staging. Stage Ia1 The depth of stromal invasion should not exceed 3 mm and the horizontal diameter should not exceed 7 mm The depth of stromal invasion is greater than 3 mm but should not exceed 5 mm and the horizontal diameter should not exceed 7 mm.
Stage Ia2
Stage Ib
Clinical lesions confined to the cervix or preclinical lesions greater than Ia Stage Ib1 Stage Ib2 Clinical lesions not greater than 4 cm in diameter Clinical lesions greater than 4 cm in diameter
Stage II
The carcinoma extends beyond the cervix, to the parametria, but has not reached the pelvic wall. The carcinoma extends to the vagina, but has not reached the lower third. Stage IIa Stage IIb Without obvious parametrial involvement. With obvious parametrial involvement.
Stage III
The carcinoma extends to the pelvic wall. On rectal examination, there is no cancer-free space between the tumour and the pelvic wall. The tumour involves the lower third of the vagina. All cases with hydronephrosis or nonfunctioning kidney are included, unless they are known to be due to some other cause. Stage IIIa Stage IIIb Without extension to the pelvic wall. With extension to the pelvic wall and/or hydronephrosis or nonfunctioning kidney.
-317-
Manual on the prevention and control of common cancers
Stage IV
The carcinoma extends beyond the true pelvis or clinically involves the mucose of the bladder or the rectum. A bullous oedema as such does permit a case to be alloted to Stage IV. Stage IVa Stage IVb Spread to adjacent organs Spread to distant organs.
Stage Grouping Stage O Stage 1A1 Stage 1A2 Stage 1B1 Stage 1B2 Stage IIA Stage IIB Stage IIIA Stage IIIB Tis T1a1 T1a2 T1b1 T1b2 T2a T2b T3a T1 T2 T3a T3b Stage IVA Stage IVB T4 Any T NO NO NO NO NO NO NO NO N1 N1 N1 Any N Any N Any N MO MO MO MO MO MO MO MO MO MO MO MO MO M1
-318-