5-ARIs in prevention of prostate cancer — an update


The recent publication of an article on trends in the prescription of finasteride has re-stimulated the debate on the use of 5α-reductase inhibitors (5-ARIs) like finasteride and dutasteride in the prevention of prostate cancer.

It was in 2003 that the original results of the Prostate Cancer Prevention Trial (PCPT) were published in the New England Journal of Medicine. Those results showed a 25 percent reduction in the risk for prostate cancer in men > 55 years of age who received finasteride as opposed to a placebo (a sugar pill).

The new article by Hamilton et al. in Cancer Epidemiology, Biomarkers and Prevention is based on an assessment of the trends for prescriptions of finasteride at Veterans Health Administration (VHA) clinics between January 2000 and December 2005.  However, it wasn’t until 2009 that the American Urological Association and the American Society for Clinical Oncology published a joint guideline suggesting the potential appropriateness of 5-ARIs in the prevention of prostate cancer.

Hamilton et al. report that by 2005, urologists and primary care physicians still weren’t prescribing finasteride with enthusiasm for the prevention of prostate cancer. This is hardly a big surprise. A thorough discussion of the paper by Hamilton et al. and related issues is presented in an article on Medscape, and we recommend this article to the interested reader. In 2005 the finasteride data were only a year or so old, and there was controversy about the possibility of a slight increase in risk for more advanced forms of prostate cancer among patients being treated with finasteride. Today, 5 years later, extensive analysis has demonstrated that that apparent increase in risk is not real, and a second trial, the REDUCE trial, has shown that dutasteride has an almost analogous effect on risk for prostate cancer as finasteride — in a slightly higher risk group of patients.

What is of concern to The “New” Prostate Cancer InfoLink is the continuing split in the urologic oncology community (and in the larger medical community) about the value of 5-ARIs in the prevention of prostate cancer. Some in the urology community continue to argue either that the effect demonstrated in the PCPT trial and in the REDUCE trial is “not real” or that the value of this type of therapy is still not sufficiently substantiated. This continuing unwillingness of some senior members of the urologic oncology community to support the data from the PCPT — at least for those patients at a significant risk for a subsequent diagnosis of prostate cancer — is worrisome.

For decades we have treated men with high blood pressure with all sorts of therapies to reduce their risk for cardiovascular illnesses. We give men statins to prevent heart attacks. Men stay on these drugs for decades. Do these drugs have side effects? Yes, of course they do, but most clinicians consider that the benefit of preventing serious cardiovascular disease is worth the relatively small risks associated with the side effects. And that’s just one general area where preventive drug therapy has become completely accepted and customary.

In the case of the 5-ARIs, there is > 20 years of experience in giving these drugs as treatments to men who have benign prostatic hyperplasia (BPH). The adverse effects associated with these drugs appear to be well-defined, and limited to a relatively small subset of patients. Furthermore, those side effects appear to be reversible if the patient finds the side effects difficult or unacceptable to live with.

The “New” Prostate Cancer InfoLink does not think that every man with a PSA > 2.5 or 3.0 ng/ml needs to get treatment with a 5-ARI to lower his risk for prostate cancer. But we do think there are definable groups of patients for whom preventive therapy is a real opportunity. We would suggest that such definable risk groups include men with at least two widely accepted risk factors (e.g., a family history of prostate cancer and an PSA level of > 2.5 ng/ml).

The differences of opinion within the urologic oncology may not be serving the best interests of patients who might benefit the most from the failure to reach a consensus about the potential of 5-ARIs as preventive agents in the management of prostate cancer risk. It is beyond our simple capabilities to be able to resolve these differences of opinion, but it seems odd to us that the AUA and ASCO can draft and disseminate a guideline to their members, and yet the actual acceptance of that guidance is stalled by the opinion of a subset of the community.

It is hardly surprising that the primary care community has yet to “get” the message about the potential of 5-ARIs when the specialist prostate cancer community is still debating the issue 7 years after publication of the PCPT data. And it makes one wonder how many men have received a radical prostatectomy or radiation therapy for low-risk prostate cancer this year whose health might have been better managed with a daily pill that could have saved them from an unnecessary biopsy.

2 Responses

  1. Bravo! Well explained. Time for a wake-up call and catch-up time for those urologists and oncologists who have been dragging their feet in keeping up with their colleagues who have dedicated much of their time to particular research and study of medications that can serve not only to prevent the development of prostate cancer, but to also prolong the lives of those whose cancer has already failed the usual treatment options. It will be physicians like these, in consort with the scientific research community, who will one day determine that elusive marker that will totally stop prostate cancer from even beginning development.

  2. Bravo from me too!

    Thanks for a nice presentation of this important topic.

    Regarding the question of which men should take one of these drugs for prevention — an important and somewhat challenging issue at this point, how about considering that men with indications of “hereditary” prostate cancer should take one of the drugs, even if that is the only risk factor. I’m using “hereditary” in the technical sense, as a more risky subset of the familial risk pattern.

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