AUSSIE ONCOLOGISTS CRITICIZE CHEMOTHERAPY - PART ONE
An important paper has been published in the journal Clinical Oncology. This meta-analysis, entitled "The Contribution of Cytotoxic Chemotherapy to 5-year Survival in Adult Malignancies" set out to accurately quantify and assess the actual benefit conferred by chemotherapy in the treatment of adults with the commonest types of cancer. Although the paper has attracted some attention in Australia, the native country of the paper's authors, it has been greeted with complete silence on this side of the world.
All three of the paper's authors are oncologists. Lead author Associate Professor Graeme Morgan is a radiation oncologist at Royal North Shore Hospital in Sydney; Professor Robyn Ward is a medical oncologist at University of New South Wales/St. Vincent's Hospital. The third author, Dr. Michael Barton, is a radiation oncologist and a member of the Collaboration for Cancer Outcomes Research and Evaluation, Liverpool Health Service, Sydney. Prof. Ward is also a member of the Therapeutic Goods Authority of the Australian Federal Department of Health and Aging, the official body that advises the Australian government on the suitability and efficacy of drugs to be listed on the national Pharmaceutical Benefits Schedule (PBS) รขโฌโ€ roughly the equivalent of the US Food and Drug Administration.
Their meticulous study was based on an analysis of the results of all the randomized, controlled clinical trials (RCTs) performed in Australia and the US that reported a statistically significant increase in 5-year survival due to the use of chemotherapy in adult malignancies. Survival data were drawn from the Australian cancer registries and the US National Cancer Institute's Surveillance Epidemiology and End Results (SEER) registry spanning the period January 1990 until January 2004.
Wherever data were uncertain, the authors deliberately erred on the side of over-estimating the benefit of chemotherapy. Even so, the study concluded that overall, chemotherapy contributes just over 2 percent to improved survival in cancer patients.
Yet despite the mounting evidence of chemotherapy's lack of effectiveness in prolonging survival, oncologists continue to present chemotherapy as a rational and promising approach to cancer treatment.
"Some practitioners still remain optimistic that cytotoxic chemotherapy will significantly improve cancer survival," the authors wrote in their introduction. "However, despite the use of new and expensive single and combination drugs to improve response rates...there has been little impact from the use of newer regimens" (Morgan 2005).
The Australian authors continued: "...in lung cancer, the median survival has increased by only 2 months [during the past 20 years, ed.] and an overall survival benefit of less than 5 percent has been achieved in the adjuvant treatment of breast, colon and head and neck cancers."
The results of the study are summarized in two tables, reproduced below. Table 1 shows the results for Australian patients; Table 2 shows the results for US patients. The authors point out that the similarity of the figures for Australia and the US make it very likely that the recorded benefit of 2.5 percent or less would be mirrored in other developed countries also. (NB: We apologize for the poor image quality of these tables.)
Results for Australian patients
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Results for US patients
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Basically, the authors found that the contribution of chemotherapy to 5-year survival in adults was 2.3 percent in Australia, and 2.1 percent in the USA. They emphasize that, for reasons explained in detail in the study, these figures "should be regarded as the upper limit of effectiveness" (i.e., they are an optimistic rather than a pessimistic estimate).
Understanding Relative Risk
How is it possible that patients are routinely offered chemotherapy when the benefits to be gained by such an approach are generally so small? In their discussion, the authors address this crucial question and cite the tendency on the part of the medical profession to present the benefits of chemotherapy in statistical terms that, while technically accurate, are seldom clearly understood by patients.
For example, oncologists frequently express the benefits of chemotherapy in terms of what is called "relative risk" rather than giving a straight assessment of the likely impact on overall survival. Relative risk is a statistical means of expressing the benefit of receiving a medical intervention in a way that, while technically accurate, has the effect of making the intervention look considerably more beneficial than it truly is. If receiving a treatment causes a patient's risk to drop from 4 percent to 2 percent, this can be expressed as a decrease in relative risk of 50 percent. On face value that sounds good. But another, equally valid way of expressing this is to say that it offers a 2 percent reduction in absolute risk, which is less likely to convince patients to take the treatment. (My oncologist said that by taking chemo รขโฌล“you have a 30% chance of it not returning. But what he should have made sure that I understood is that by taking chemo รขโฌล“you have a 70% chance of re-occurrence!!!รขโฌย)
It is not only patients who are misled by the overuse of relative risk in reporting the results of medical interventions. Several studies have shown that physicians are also frequently beguiled by this kind of statistical sleight of hand. According to one such study, published in the British Medical Journal, physicians' views of the effectiveness of drugs, and their decision to prescribe such drugs, was significantly influenced by the way in which clinical trials of these drugs were reported. When results were expressed as a relative risk reduction, physicians believed the drugs were more effective and were strongly more inclined to prescribe than they were when the identical results were expressed as an absolute risk reduction (Bucher 1994).
Another study, published in the Journal of Clinical Oncology, demonstrated that the way in which survival benefits are presented specifically influenced the decision of medical professionals to recommend chemotherapy. Since 80 percent of patients chose what their oncologist recommends, the way in which the oncologist perceives and conveys the benefits of treatment is of vital importance. This study showed that when physicians are given relative risk reduction figures for a chemotherapy regimen, they are more likely to recommend it to their patients than when they are given the mathematically identical information expressed as an absolute risk reduction (Chao 2003).
The way that medical information is reported in the professional literature therefore clearly has an important influence on the treatment recommendations oncologists make. A drug that can be said, for example, to reduce cancer recurrence by 50 percent, is likely to get the attention and respect of oncologists and patients alike, even though the absolute risk may only be a small one - perhaps only 2 or 3 percent - and the reduction in absolute risk commensurately small.
TO BE CONCLUDED, WITH REFERENCES, NEXT WEEK
--Ralph W. Moss, Ph.D.