April 1, 2010
Pitfalls in Prostate Cancer Prevention
My regular readers know the controversies and challenges posed by prostate cancer. It is very common. Over half the men who die at advanced age of other causes will have prostate cancer on autopsy. It is very slow. From the time that prostate cancer is detectable on biopsy to the time that it causes symptoms or shortens life can be as long as a decade. It is not very lethal. Because it tends to affect older men, most men diagnosed with it tend to die of other causes. Though it does kill tens of thousands of men annually, it kills fewer (and older) people than colon cancer, lung cancer or breast cancer (or traffic accidents).
This confluence of a very common but very indolent disease that strikes mostly older men has made screening, diagnosis and treatment very challenging. Should we be testing for a disease that lots of people will get but that most people won’t be harmed by? No one knows yet.
These challenges have prompted some researchers to consider prevention. What if instead of testing, diagnosing and treating we could give men at high risk of prostate cancer a medicine that made prostate cancer less likely? To be more cynical, the finances are also tempting since many more “at risk” men would have to take a preventive medicine than would actually get prostate cancer.
A large study published in this week’s New England Journal of Medicine shows that dutasteride, sold under the brand name Avodart, can decrease the incidence of prostate cancer in some men. This has received much media attention. (See links below.) But let’s review the details before prescribing it to your uncle and grandpa.
The study enrolled over 8,000 men who were thought to be at high risk for prostate cancer because of their age or an elevated PSA. (PSA is a not-very-accurate blood test used to test for prostate cancer.) They all had a prostate biopsy at the beginning of the study and only those with negative biopsies (i.e. no detectable cancer) were enrolled. Half the men were randomized to take Avodart daily, and half to placebo. All the men had prostate biopsies two years and four years after enrollment. The study sought to find if there was a difference in the numbers of prostate cancers found in the biopsies of the two groups.
Sure enough, Avodart seemed to decrease the incidence of prostate cancer found in the biopsies. 20% of the men taking Avodart were found to have prostate cancer versus 25% of the men taking placebo. But so what? Not a single person in either group died of prostate cancer, and they wouldn’t have been expected to since the study lasted four years and prostate cancer takes much longer than that to cause harm.
There’s absolutely no way to know if the men taking Avodart will live longer or be spared the symptoms of prostate cancer without following them for a much longer time. There is good reason to suspect that the men taking Avodart won’t do much better than the men taking placebo. The number of very aggressive tumors (as measured by their Gleason score, a quantitative score related to the tumors’ microscopic appearance) was the same in each group. It was only the least aggressive tumors that were decreased in the Avodart group.
Moreover, about 5% more men in the Avodart group than in the placebo group developed problems with libido or with erections. So for every 20 men who take Avodart rather than placebo for 4 years, one fewer man develops prostate cancer on biopsy which may or may not ever harm him, but one additional man develops sexual side effects. Add to that a small additional risk (about half a percent) of heart failure in the Avodart group, and the numbers are very discouraging.
An editorial in the same issue of the New England Journal of Medicine concludes that Avodart should not yet be prescribed for prostate cancer prevention. We need to know much more about the outcomes of men who take it for decades, not years.
New England Journal of Medicine article: Effect of Dutasteride on the Risk of Prostate Cancer
New England Journal of Medicine editorial: Chemoprevention of Prostate Cancer
Los Angeles Times article: Prostate drug may work as a preventive
Associated Press article: Study finds possible heart risk with prostate drug
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