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BMJ No 7128 Volume 316
News Saturday 31 January 1998
Possible new test for detecting men at risk of prostate cancer
| Researchers in North America have discovered that measuring plasma concentrations of insulin-like growth factor-1 could help to identify men who are at high risk of developing prostate cancer. The research may also offer a clue to explain why some prostate cancers develop more aggressively than others (Science1998;279:563-5).
IGF-1 is a hormone produced in the liver that both stimulates cell growth and inhibits natural cell death (apoptosis) and is critical for normal biological development and growth. High concentrations of IGF-1 encourage a rapid turnover of cells, which in turn increases the risk of a random malignant transformation of these cells into a cancer. Dr June Chan, from the Harvard School of Public Health in Boston, and her colleagues worked on the hypothesis that as IGF-1 acts on the epithelial cells of the prostate gland, men with high circulating concentrations of IGF-1 may be at higher risk of developing prostate cancer than men with lower concentrations. |  | |
| Britain has no national screening programme for prostate cancer Photo: MARK HENLEY/IMPACT |
To test this theory, the team looked at men who are currently participating in the physicians' health study and identified all those who had developed prostate cancer since entering the study in 1982. They found that for 152 of these men they had enough frozen plasma left to measure both IGF-1 and prostate specific antigen concentrations. Prostate specific antigen is a marker of prostate cancer currently used to diagnose and monitor the disease. These cases were matched with 152 controls.
"The normal range of IGF-1 is very wide, and we found that men in the top 25% of our sample were 4.3 times more likely to develop prostate cancer than those in the bottom 25% of the range," said Dr Chan. "This appeared to be true regardless of the baseline prostate specific antigen level." The same correlation existed with both high and low grade cancers, and it looks likely to be even stronger for men over the age of 60.
Dr Michael Pollak, a clinical oncologist on the research team who is based at McGill University in Montreal, insists that this does not make measuring concentrations of prostate specific antigen redundant but suggests that IGF-1 concentrations taken in conjunction with specific antigen measurements may offer a much better prediction of risk than antigen measurements alone. Measuring circulating IGF-1 could therefore help to identify a high risk population of men, who should be monitored much more vigilantly than those men with IGF-1 concentrations at the lower end of the range.
Dr Pollak believes not only that IGF-1 is a significant risk factor for prostate cancer but that it may also determine the natural course of the disease. "So it may turn out that IGF-1 levels will be useful in advising clinicians when watchful waiting is inappropriate, and when they should offer immediate surgery or radiotherapy," he said. However, clinical features of overt cancer, such as capsule invasion, will obviously remain a critical determinant of when active treatment is necessary.
However, Dr John Muir Gray, director of research and development at Anglia and Oxford region of the NHS Executive and joint manager of the national screening committee, said: "There is no good quality evidence to show any benefits of prostate screening. All screening programmes do harm, and on the evidence we have so far, it would do more harm than good," he said. "The science of prognostication needs refining before we could take the results of studies like this seriously - all that glitters is not gold. Before this assay is used in clinical practice I'd want to see some concrete evidence that it results in a reduction in all cause mortality and deaths from prostate cancer."
Another implication of the study in Scienceis that a targeted risk reduction strategy may eventually become available. If the results are replicated with larger numbers of men then it may be possible to reduce the risk of prostate cancer by administering drugs that counteract the effects of IGF-1 in those men with the highest concentrations of the hormone.
The association of high IGF-1 and an increased risk of cancer is unlikely to be restricted to the prostate gland. Dr Pollak has also been involved in a study of breast cancer. Early results from the nurses health study, which were presented at the 1997 annual meeting of the American Association of Epidemiology in Edmonton, are highly suggestive of a similar magnitude of correlation between IGF-1 and the risk of premenopausal breast cancer.
Abi Berger
BMJ
Britain and the United States have very different approaches to prostate cancer. As yet Britain has no national screening programme for prostate cancer. This is largely because several unanswered questions remain about how prostate cancer is detected, the natural course of the disease, and how it should be treated when it is found.
However, in the United States asymptomatic screening for prostate cancer - which uses concentrations of prostate specific antigen as a screening tool - is widespread. Despite the lack of understanding about the natural course of the disease, the North American philosophy of screening is based on a fear of missing a single cancer, rather than on the anxiety caused by subjecting men to investigations and treatment which they may not need and which have potentially damaging side effects.
In Britain, measurement of prostate specific antigen is restricted to men who present with symptoms of prostate problems. According to the NHS Centre for Reviews and Dissemination in York, there are still no reliable evaluations of the effect of treatments for early prostate cancer on mortality. And without good evidence about useful treatments, there are no grounds to establish a national screening programme.
One randomised controlled trial of treatment for early prostate cancer (known as PRO6), set up by the Medical Research Council in 1994, was forced to close prematurely in 1996 because of a lack of patients. However, a new British trial is planned, funded by the NHS Health Technology Assessment programme.
Meanwhile, the Health Technology Assessment programme has shortlisted three proposals for a randomised controlled trial of prostatic specific antigen as a single screening tool for prostate cancer. This trial is likely to start at the end of 1998.
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