This is a book about the advances made in the treatment of cancer, especially in its management by medical means – a branch of medicine known as medical oncology. Anyone who writes a book about cancer must bear in mind that many of its readers will be patients who have the disease or their relatives and close friends. Some of them will read it in fearful anticipation of what they will learn and of the loss of hope it may entail. The author has a special responsibility to such readers. Yet, as the book shows, it is difficult, even for those treating cancer, to be calm and objective about the disease. Cancers are common, and often, but not always fatal. The disease inspires dread in the mind of the public. It also presents scientists and doctors with some of the most difficult problems in medicine.
The malignant transformation of cells is a process that involves events of great biological complexity, many of which are badly understood and the subject of vigorous debate. The treatment of cancers is becoming highly technical and changing fairly rapidly so that even specialists find it difficult to keep informed. Furthermore, the emotions which the subject arouses sometimes persuade clinicians to make premature or ill-founded claims for treatments – as in the case of Interferon or immunotherapy – and often lead to public controversy over tentative or speculative theories of causation, such as stress, diet, industrial poisons, food additives, viruses.
The problems which surround breast cancer are an example of these difficulties. The cause of the disease is unknown, although many factors, including geographical, reproductive and social influences, have been shown to produce a slight increase in risk. Attempts at early detection are still being evaluated, and it is not yet clear what benefit ‘screening’ will produce. The operative approach to the disease is changing from radical surgery to less mutilating procedures as it becomes more evident that survival is determined largely by whether the disease has spread before the surgeon operates. In recent years attempts have been made to conserve the breast by using radiotherapy but it is not yet clear in which women it is safe to do this. Lastly there is great interest in using chemotherapy (drugs which kill cancer cells) and hormone therapy after surgery in order to prevent recurrence, rather than reserving them until relapse has occurred.
The recognition that this and many other types of cancer have spread (metastasised) at the time of diagnosis has led to a considerable expansion of medical oncology, in which systemic treatments such as chemotherapy are used in an attempt to destroy cancer cells throughout the body, while local control of the primary tumour is achieved by the surgeon or radiotherapist. The specialty has grown rapidly in the USA, where it is considered the province of the physician. This is partly because surgeons and radiotherapists are regarded as specialising in local treatments while physicians traditionally deal with drugs of all types. It is also a reflection of the historically weak position of radiotherapy in the USA, where it has been given by the same doctors who are responsible for diagnostic radiology (chest X-rays and so forth). In the UK, radiotherapy has for many years been a strong and independent discipline. Here, after a long and complicated training, radiotherapists become highly expert in cancer management and, as a result, many of them see no reason why the responsibility for drug treatments should be assigned to physicians. Ideally, medical oncologists, radiotherapists and surgeons should all collaborate in patient management: in my own hospital I see patients jointly with my radiotherapist colleagues. For all these reasons – emotional, biological, clinical, political – writing about cancer is a difficult business and whoever attempts to do so has to cross some very difficult territory. Dr Israel, however, is not lacking in confidence. Indeed, he charges in, banner held high. Dr Israel, who is head of a medical oncology unit in Bobigny in France, has no doubt whatsoever that systemic treatments are working in most tumours and that the time will come when cancer is conquered – largely by the medical oncologists. He believes that there is an ‘intolerable discrepancy between the way in which cancer patients are treated today and the way in which they could be treated’.
In the first section of his book Dr Israel dwells in some detail on the natural history of malignant tumours and shows how, for many cancers, the tumour is far advanced in its lifespan (that is, has doubled in size more than 30 times) before it is clinically detectable – after a total of 40 doublings it is fatal. Since the potential for metastasis is presumably present early on, the benefit to be derived from detecting tumours ‘early’ by clinical examination may be marginal. This does not deter Dr Israel from recommending that ‘gynaecologists, gastroenterologists, specialists in disease of the lungs, the larynx, the urinary organs, and so forth, should examine the target organ in adults every six months or every year.’ The social and medical implications of this statement are such as to make it difficult to take seriously. Many scientists and oncologists would question other arguments in this section. For example, Dr Israel’s faith in the ability of tumours to excite a useful immune response in the host is not shared by many immunologists, and since this is central to his belief in the powers of ‘immunotherapy’ it should be taken with considerable reservations.
In the next section he deals with conventional treatments such as surgery and radiotherapy. While much of what he has to say concerning the limitations of these local treatments in dealing with a disease which may have spread is correct, I found many statements unguarded and overemphatic. He says, for instance, that a medical oncologist should see every patient before surgery and ‘elaborate a strategy’ for treatment: surgeons would be justified in asking what a medical oncologist had to offer, post-operatively, in the majority of cancers of the lung, in cancer of the large bowel, the uterus, pancreas and kidney, all of which are notoriously resistant to medical treatment.
Here we come to the core of the book and of Dr Israel’s thesis. Can medical oncologists deliver the goods? He reviews the action and nature of cytotoxic drugs and describes how they may be used both in advanced disease as palliation, but without hope of cure, and as a prophylactic against recurrence when given immediately after surgery. It is true that chemotherapy has made great advances and has achieved cures in certain uncommon, highly sensitive tumours. These include childhood leukaemia, solid tumours in children, lymphomas including Hodgkin’s disease in adults, and tumours of the testis. The chance of cure may be improved by early chemotherapy after surgery in breast and ovarian cancer but it is too early to be certain. There are, however, large numbers of advanced cancers in which the chances of a useful response with chemotherapy are almost negligible. Dr Israel believes that, even then, no one should be denied treatment in case it works. I understand his point of view but do not share it. The treatment is usually toxic, in spite of his over-optimistic reassurances that the toxicity has diminished in the last five years. Every physician worth his salt is reluctant to administer unpleasant treatment with a small chance of only temporary relief to an incurable patient.
In the chapter on immunotherapy, which is the other technique Dr Israel claims for the oncologist, there is little recognition of the uncertainties which surround this approach. There hasn’t been much reputable work to indicate that manipulation of the immune response as currently practised has any part to play in the management of malignancy. The use of vaccines of micro-organisms and of killed tumour cells has had its proponents, including himself, but the results are variable and unsatisfactory. The problem is that it now appears that, unlike tumours produced by chemicals or viruses in animals, spontaneous tumours do not excite specific immune responses which can be detected by current techniques. Immunotherapy of cancer will have no firm scientific basis until the techniques for detecting and analysing the immune response improve, or non-specific methods of attack are perfected.
In the last chapters Dr Israel discusses the ethical issues that arise in talking to cancer patients and in the conduct of clinical trials as well as those that surround charlatan remedies. The book is worth reading for this section alone: the work of an enthusiastic, humane and thoughtful physician who wants to help his patients and at the same time advance his subject. He has nothing but justified contempt for those who peddle instant remedies (laetrile, dietary restrictions, vaccines and so on) and who trade on the longings of vulnerable people. Clinical investigation, with all its difficulties and uncertainties, provides less instant comfort, but is the only way ahead. Where I find myself sometimes parting company with Dr Israel is in his evaluation of the data which have come from clinical trials. Many of these studies have methodological weaknesses, and it would be wise to adopt a more cautious attitude to some of the claims of chemotherapists and immunotherapists.
The book is highly personal in tone with repeated, self-congratulatory references to Dr Israel’s own work and to that of his colleagues and friends. The language is often imprecise and the arguments ill-ordered, and it is difficult to agree with Susan Sontag’s statement on the front cover that it is ‘by far the most intelligent, informative and useful book ever written on cancer’.