The prevention of prostate cancer with 5α-reductase inhibitors (5-ARIs)

In late February 2009, the American Society for Clinical Oncology (ASCO) and the American Urological Association (AUA) published a joint guideline that made two core recommendations regarding the prevention of prostate cancer. These recommendations are based on an extensive review of all the available literature, but most specifically the data from the Prostate Cancer Prevention Trial (PCPT).

We have to assume that at the time of writing of this guideline, the authors were also already aware of the then unannounced results of the REDUCE trial.

The two core recommendations in the guideline are as follows:

  • Men with a PSA score of 3.0 ng/ml or below who are screened regularly (or plan to get yearly PSA tests) and currently show no signs of prostate cancer are encouraged to talk with their doctor about the risks and benefits of taking a 5-ARI to further prevent their likelihood of getting prostate cancer.
  • Men who are already taking a 5-ARI for other conditions should talk to their doctor about continuing to use this drug for the prevention of prostate cancer.

This guideline represents the first time ever that any medical organization has issued any guideline suggesting that it may be possible to prevent prostate cancer, and the way in which the guideline expresses its two recommendations reflects the caution of the guideline committee in making these recommendations.

What is a 5-ARI? There are two 5-ARIs currently approved in the USA for the treatment of benign prostatic hyperplasia: finasteride (originally marketed as Proscar but now available generically) and dutasteride (Avodart/GlaxoSmithKline). The guideline does not differentiate between the potential of these two agents to prevent development of prostate cancer.

Why did it take so long for ASCO and the AUA to issue this guideline? The PCPT trial was competed years ago!

There were data in the results on the Prostate Cancer Prevention Trial that suggested the possibility that long-term finasteride therapy might be inducing an increased risk for higher-grade prostate cancer among the men who did get prostate cancer in the PCPT. The results of the REDUCE trial both confirmed the results of the PCPT trial (in a group of men at somewhat higher risk for development of prostate cancer) and also indicated a very small increase in risk for development of aggressive forms of the disease.

Now The “New” Prostate Cancer InfoLink is not as constrained by the caution of the joint guideline committee, and we would like to add some information for readers that was not explicitly addressed in the full text of this guideline.

The “New” Prostate Cancer InfoLink believes that the new guideline is particularly important for men who meet any one of the following criteria:

  1. You are 45 years or older and have a family history of prostate cancer (father, brother, or grandfather).
  2. You are of African American or Afro-Caribbean ethnicity, aged 40 years or older, with a low PSA and no specific signs or symptoms suggestive of prostate cancer.
  3. You are a man who had a baseline PSA value > 1.5 ng/ml at age 35-45 years of age.
  4. You are a man of any race of 50 or older who has no specific signs or symptoms of prostate cancer but who already needs or is already having treatment for BPH with a 5-ARI.
  5. You are a man of any race of 50 years or older whose fear and anxiety about the possibility of definitive therapy for prostate cancer at some time later in life is such that you are liable to avoid regular testing to ensure early diagnosis of this disease.

Criteria 1-3 above are all known to place individual patients at increased risk for prostate cancer. Criterion 4 is specific to the second recommendation of the ASCO/AUA guideline committee. Criterion 5 addresses the subset of men whose fear of treatment places them at the greatest risk for avoiding early diagnosis and therefore at the highest risk for later diagnosis with progressive and incurable disease.

For all such patients, the ability to take a 5-ARI opens the door to potential avoidance of not just prostate cancer but also unnecessary biopsies.

Having said that, we also know that 5-ARI treatment significant lowers PSA levels in patients receiving this drug. This suggests to us that patients being treated with a 5-ARI for the prevention of prostate cancer should also talk to their doctors about the value of regular (perhaps annual) PSA tests assessed using an ultrasensitive PSA test in order to monitor any changes in PSA levels with the greatest possible level of accuracy.

So let’s look at the pros and the cons of 5-ARI therapy to prevent prostate cancer. On the “plus” side:

  • Daily finasteride or dutasteride therapy very definitely reduces risk for prostate cancer — by about 25 percent.
  • Certainly tens of thousands (and probably millions) of men have taken 5-ARIs daily  for years to treat benign prostatic hyperplasia or BPH (an enlarged prostate), and there has been no suggestion that these men have demonstrated increased risk for diagnosis with either prostate cancer or higher grades of prostate cancer in the 15 years since finasteride was first approved.
  • The original authors of the PCPT have suggested sound potential explanations for why there appears to have been an increased risk for high grades of prostate cancer in the PCPT, while suggesting that this may not actually be the case.

And on the minus side:

  • Long-term daily use of finasteride or dutasteride in men over 55 appears may increase risk for higher grades of prostate cancer in some men who actually get diagnosed with prostate cancer, but this opinion is now held by a minority of physicians who actually specialize in the management of prostate cancer.

The “New” Prostate Cancer InfoLink has long argued in favor of an appropriate guideline that recommended the appropriate use of either finasteride alone or 5-ARIs in general for the prevention of prostate cancer, based on the data from the PCPT. The guideline as written is by no means as emphatic as we would have hoped for, but this is understandable under the circumstances.

We would make the final point that if sufficient men were to take advantage of this guideline and talk to their doctors about the potential of using 5-ARI therapy to cut their individual risk of prostate cancer, we might reduce the annual incidence of prostate cancer in the USA from nearly 200,000 per year to more like 150,000 per year, and the annual number of deaths from > 26,000 to more like 21,400 in a matter of years.

Content on this page last reviewed and updated March 26, 2011
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