Progress against cancer

Print edition : August 09, 1997

There have been significant gains in cancer treatment; at the same time, no effort should be spared to provide state-of-the-art treatment to all those who need it.

IN medicine, especially in the treatment of cancer, the concept of progress is difficult to define. If the yardstick to measure progress is the impact that recent scientific information has made on the overall control and cure of cancer, then the last 25 years, which witnessed an explosion in basic scientific knowledge, have seen significant changes in the approach to cancer control and cure. From an era of total fatalism in the 1960s, when cancer was considered incurable and invariably fatal, today we talk not only of cure and long-term survival but of prevention and control.

Conceptual influences have played a major role in these achievements: a better understanding of the natural history and evolution of disease, of the definition and concepts of early-stage disease, and of micro metastases, occult disease and minimal residual disease. Studies in fundamental biology and molecular biology techniques have not only enhanced diagnostic capabilities but have also played a significant role in cancer prevention and treatment. All these have contributed in no small measure to the formulation of therapeutic strategies based on the biology of the tumour set against the backdrop of the host milieu.

An overview of all this will be voluminous. I shall confine myself to a few areas of progress relevant to common cancers in India, and as may be of interest and relevance generally.

In the outpatient lobby of the Cancer Institute in Chennai. South India's first comprehensive cancer centre and the country's second, the Institute has consistently laid emphasis on advanced medical care and research in the field, bringing refined scientific technology and patient care to the poorest in the land.-K. GAJENDRAN

BY SPECIAL ARRANGEMENT

Dr. S. Muthulakshmi Reddy (1886-1968), the first woman in India to graduate in medicine in 1912. In 1955 she founded the Cancer Institute in Chennai. Dr. Muthulakshmi Reddy, who was a member and vice-president of the Madras Legislative Assembly during 1927-30, resigned from the Assembly in protest against the arrest of Mahatma Gandhi at Dandi in 1930.

THE commonest cancers in India are those affecting the mouth, the throat and the stomach in the case of men and the uterine cervix and the breast in the case of women. The transition of a normal epithelium to a cancerous one is a gradual process, spread over decades, passing through distinct and well defined phases. The study of the evolution of cervical cancer through phases of mild, moderate and severe dysplasia to cancer-in-situ (pre-cancer stage) and on to invasive cancer was made possible by the introduction of cytology, the study of cells. When dysplasia is detected, it is possible to reverse it by treatment and prevent progression to cancer. Such epithelial change can be recognised in the cervix, the oral cavity, the bronchial epithelium, the oesophagus and the bladder. This understanding and facility laid the foundations of preventive oncology and the concept of health screening to identify asymptomatic lesions in an effort to prevent cancer.

Cancer prevention can be primary or secondary. Primary prevention involves the removal of carcinogenic or implicated causative factors such as tobacco, improvements in education and water supply and a balanced diet. Most of these involve a change in lifestyle. This needs social and legislative action, and any impact can be felt only after a long period.

Secondary prevention is therefore of utmost importance. This involves the identification and treatment of asymptomatic individuals with either pre-clinical or early cancer by means of health screening. Screening is a significant step in cancer control, the objective being detection at the pre-cancer stage so that pre-cancerous lesions do not progress into cancer as in cervical cancer. In case of very early detection of cancer in the pre-palpable, pre-visual stage, cure to the extent of 80 per cent to 90 per cent is possible. The use of specific tumour markers can identify women at high risk of breast cancer. The identification of familial risk in colon cancer and PSA (prostate specific antigen) for prostatic cancer is also possible.

Today, early detection is that which is done only cytologically, or even better, at the molecular level. The necessary techniques are available for all this. The cancers that can be detected through screening programme are uterine cervix, breast, colorectum and prostate. The greatest impact of screening programmes has been on cervical cancer and breast cancer.

SCREENING mammography has effectively increased the number of cases detected in the early and very early stages, sometimes even before it is palpable to the most experienced fingers. The lesion can be detected when it is just a few millimetres in size or seen only as specks of calcification. Cancer so detected has a cure rate of over 95 per cent. The benefit is not just in terms of cure and survival but cure without morbidity. The lesions are excised by sterotaxic surgery without causing any mutilation.

Mammographic detection of breast lesions is possible two to four years before clinical detection is possible. Extensive screening programmes involving thousands of women in affluent countries such as the United Kingdom and the United States have documented significant benefits in terms of both early detection and improved survival in the case of breast cancer for women over 40.

Screening mammography is not advised before the age of 40 except under special circumstances. Screening of the contralateral breast in women who have had cancer of the breast and in women with a family history of breast cancer is essential.

Studies have shown that a woman with a family history of breast cancer either in her mother or sister (first degree relatives) or aunt or cousin (second degree relatives) has a higher risk of developing breast cancer than one who has no such family history. The risk is three-fold when one first degree relative has had cancer, six-fold when two first degree relatives have had cancer. It is 1.5 times for second degree relatives.

Over the past decade, molecular genetics has thrown considerable light on the nature of breast cancer and risk identification. Breast cancer is now known to be caused by an abnormality in the DNA of the breast epithelium and the causative gene has been identified.

Breast cancer occurring in families is now known to be caused by abnormalities in two genes - BRCA 1 and BRCA 2. BRCA 1 abnormality increases the risk of ovarian cancer as well.

It is possible today to study genetic markers of cancer susceptibility. The benefits of such study would include reduction in uncertainty since everyone need not be a carrier of the hereditary predisposition; non-carriers can thus be identified. When carriers are identified they could be counselled on treatment options and may be considered for targeted chemoprevention.

Married women over the age of 30 constitute the risk group for uterine cervical cancer. Those in the lower socio-economic group and sex workers are particularly susceptible. More recently, the human papilloma virus has been implicated in cervical carcinogenesis. It is reported that 96 per cent of those with cervical dysplasias are HPV positive. HIV positive women are at high risk for HPV infection and therefore have increased risk of cervical cancer.

Large-scale screening programmes using the Pap smear have shown that annual screening can reduce the risk of a woman developing cancer by 93.5 per cent; screening once every three years reduces the risk by 91.2 per cent. It is, therefore, recommended that low-risk women can have the screening once in three years and high-risk women once a year.

An annual gynaecological examination and PaP smear is recommended for all sexually active women. It is an outpatient procedure and the cost is minimal. Treatment for the pre-cancer stages in the case of the cervix involves only improvement in genital hygiene in addition to local conservative management, at most a hysterectomy.

THE concept of diet as a possible etiologic factor in certain cancers was derived from the differential world pattern of cancer incidence and confirmed by basic carcinogenesis studies. The implicated diet factors are calorie intake, fat content, fibre content and micro-nutrients. Cancers of the colorectum, breast, stomach, ovary, endometrium, lungs and so on are all considered to be influenced by dietary factors. International trials and chemo prevention trials are under way in the affluent countries.

Chemoprevention attempts to block the initial initiation of the carcinogenic process or to arrest or reverse the progress of premalignant lesion before it becomes invasive.

Trials involving thousands of patients are now exploring the possibility of prevention of cancer of the breast, the colon, the prostate and the lungs. The agents being assessed are retinoids, tamoxifen, antioxidents, and so on.

Cruciferous vegetables such as broccoli and yellow and green vegetables such as carrot and greens, contain agents that block the activation of carcinogens and thus prevent DNA damage. These help protect people against cancer.

Apart from techniques such as computerised tomography (CT) scan, nuclear imaging, magnetic resonance imaging (MRI), ultrasound scan, fibre optic endoscopy, and so on that are routine investigations today, the discovery of tumour markers, biological markers and genetic markers along with immunophenotyping and immuno histochemistry, polymerase chain reaction (PCR) to study minimal residual disease have enhanced diagnostic capabilities multifold.

Tumour markers are biological or biochemical substances produced by tumour cells that can be detected in the serum of patients. They can be specific or non-specific.

Specific tumour markers such as HCG have revolutioned the overall outlook and treatment in gestational trophoblastic tumours (chorio carcinoma). If adequately and properly monitored after a molar pregnancy, no patient need be lost to chorio carcinoma.

Most of the other tumour markers, such as alfa-feto protein for testicular cancers, PSA for prostatic cancer, CA 125 for ovarian cancer, CEA for colon cancer and many others have been found useful in treatment planning and in monitoring patients after treatment. PSA has been extensively studied as a screening assay for early detection of prostatic carcinoma in men.

PCR has revolutioned the capability to detect tumour cells. Using PCR, it is now possible to detect one tumour cell amidst a million normal cells. This has improved the sensitivity of staging procedures and the detection of minimal residual disease. Blood cancers and other cancers including breast cancer will benefit from these applications. Using PCR technology it is now possible to detect pre-malignant and early malignant lesions, as in bowel cancers.

Advances in various areas of basic research have been responsible for advances in prevention and early detection as in Pap smear, mammography, evaluation of cancer susceptibility, tumour markers and therapeutic care.

The most gratifying achievements are the chemotherapeutic cure of paediatric leukaemias, with a rise in cure rate in childhood cancers from 20 per cent in 1960 to over 70 per cent in the 1990s. Cure of Hodgkin's disease and testicular cancers are other success stories.

The introduction of effective drug therapy and the concept of multimodal treatment based on the biological needs of the tumour and the host has been responsible for significant improvement in many cancers. It has brought at least 14 types of cancer within the scope of cure. In many others, such as osteosarcomas, soft tissue sarcomas and breast cancer, it has enhanced survival.

One remarkable achievement of chemotherapy and multimodal therapy is organ conservation. It has made possible the replacement of radical surgery by more conservative surgery, laying prime stress on organ preservation and functional rehabilitation in cancer management, where mutilating and emotionally traumatising surgery was the only option 20 years ago.

Today, bone sarcomas are being treated and cured through limb conservation surgery with provision of custom-made prostheses. Planned limited surgery can replace mutilating breast removal; the larynx and the bladder need not be sacrificed in laryngeal and bladder cancers and colostomy can be avoided in rectal cancers. However, all this is possible only if the disease is in its early stages. Early detection therefore assumes vital importance.

Biological response modifiers including interferon, immunotherapy, hematopoietic growth factors and other advances in supportive care have extended the scope of cancer therapy and added a new dimension to cancer care. Bone marrow transplantation, by itself a milestone in therapeutic oncology, has been rendered safe.

Tumour targeting, akin to the use of a homing missile, is a promising approach. Molecular drug designing, based on abnormalities seen in tumour cells, is yielding newer drugs that are under evaluation. Gene therapy in the form of corrective replacement therapy (as for the p53 gene), oncogene inhibitory therapy, virally directed enzyme prodrug therapy (the Trojan horse approach), boosting the immune system using cytokine genes, have all shown promise.

NOTWITHSTANDING all the progress made, a large number of patients still go uncured for a variety of reasons, including delayed diagnosis, improper initial treatment and lacunae in existing knowledge. The hospice movement, the new concept of continuing care, is a remarkable blend of humanity and science, discarding the obsolete idea of mercy refuge. Continuing care consists of maintaining the quality of life, psychospiritual support and pain relief. This allows the afflicted individual to fade away gently and almost imperceptibly, and to do so with dignity.

No doubt there have been significant triumphs in the war against cancer over the last 25 years. The cure of many childhood cancers, Hodgkin's disease and testicular tumours, organ conservation in breast, larynx and bladder cancers are no mean achievements. Today one out of three cancer cases are cured and two out of three have the potential to be cured.

Yet if one were to assess overall progress in terms of mortality, there has been no substantial gain. Many people are alive and well today as a result of cancer research and better cancer care. Too many still do not have access to the knowledge and resources that are available. We need efforts to bring the fruits of research to all .

In the meantime, no effort should be spared to provide state-of-the-art treatment based on the achievements of the last 25 years to all who need it, irrespective of social class or nationality.

A letter from the Editor


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