Who should receive a 5-ARI to prevent prostate cancer?

The “New” Prostate Cancer InfoLink has long argued that the potential of 5α-reductase inhibition (using finasteride and dutasteride) to prevent prostate cancer is under-appreciated and under-utilized. However, we also acknowledge a lack of good data to identify those patients for whom the benefits of prevention may outweigh the risks associated with the side effects of such treatment.

Vickers et al. have now reanalyzed data from the Prostate Cancer Prevention Trial  (PCPT) to see if it is possible to address this problem. In particular, they attempted to determine whether PSA levels could be used to identify a high-risk subgroup of patients for which the benefits of finasteride treatment outweigh the potential harms.

The authors used the raw data from the PCPT to model a series of chemopreventive treatment strategies: treat all men, treat no men, or treat a high-risk subgroup based on PSA level. They applied statistically methodology to “weight” the potential benefits (the reduction in cancer risk) and the potential harms (risk for prostate cancer treatment) of each strategy.

The results of their analysis are given below:

  • Of 9,058 men treated with finasteride in the PCPT, 1,957 were diagnosed with prostate cancer during the 7-year study.
  • For the endpoint of reducing the risk of all cancers, including both for-cause and end-of-study biopsies, the optimal strategy is to treat all or nearly all men (as initially demonstrated by the PCPT )
  • To reduce risk of cancers detected through routine care, treating men with a PSA level either > 1.3 or > 2 ng/ml is optimal.
  • Treating only men with a PSA level > 2 ng/ml reduced the prostate treatment rate by 83 percent and resulted in a cancer rate only 1.1 percent higher than treating all men.

The authors state two conclusions:

  • Clinicians wishing to reduce the risk of any biopsy-detectable prostate cancer should recommend finasteride to all men.
  • Clinicians who believe that it is unnecessary to prevent all cancers, but that preventing those readily detectable by screening would be desirable, would be best off recommending finasteride only to a high-risk subgroup.

Now it should be noted that analyses like this are based on assumptions, however sophisticated the assumptions may be. The “New” Prostate Cancer InfoLink believes that Vickers and his colleagues have at least offered clinicians a testable hypothesis that can be already put into practice and that probably does come close to offering a good strategic approach to the chemopreventive use of finasteride and perhaps dutasteride too. We doubt that even the authors would be surprised if there was some variance from the 83 percent risk reduction and the 1.1 percent increase in treatments suggested by their analysis based on treatment of men with a PSA of > 2 ng/ml. Perhaps a more appropriate question to ask is, what is the annual cost of treating all men with a PSA of 2 ng/ml with finasteride compared to the annual cost of diagnosis and management with active surveillance of all men found to have indolent prostate cancer that actually turns out to be indolent.

There are also other factors that might influence this decision, inclusive of family history and ethnicity. In other words, is it possible to use a combination of PSA level, family history, and ethnicity to even better predict the benefit of prostate cancer prevention with a 5-ARI?

2 Responses

  1. Though I am a strong proponent of the use of dutasteride/Avodart (preferably) or finasteride/Proscar to accompany antiandrogens and LHRH agonists in androgen deprivation therapy, I can understand reservations by men without any sign of prostate cancer in taking either of these medications with the intent to “prevent” prostate cancer when taking note of the side effects that can accompany the administration of these medications.

    One effect I suspect many patients are unaware of and are not advised about is that men treated with dutasteride or finasteride should not donate blood until at least 6 months have passed following their last dose. As noted in the below URL, the purpose of this deferred period is to prevent administration of dutasteride or finasteride to a pregnant female transfusion recipient. I suspect another major concern is the effect either dutasteride or finasteride has on sexual issues. And, of course, another concern is the possibility of breast enlargement. And yet another note of caution is that pregnant women should NOT handle either of these medications. These and other effects should be thoroughly explained to men prior to prescribing either 5AR inhibitor for “preventive” treatment.

    Side effects from dutasteride/Avodart:
    Use caution in prescribing dutasteride/Avodart or finasteride/Proscar to patients with liver disease. The effect of hepatic impairment on dutasteride pharmacokinetics has not been studied. Because dutasteride is extensively metabolized and has a half-life of 3 to 5 weeks, caution should be used in the administration of dutasteride to patients with liver disease. Since finasteride is also extensively metabolized in the liver, the same caution applies.

  2. This is a good assessment of the issues we will increasingly face with so many health interventions. It is another situation where the good of the one may not outweigh the good of the many. Ultimately, economics may be the ultimate basis on which to make public policy decisions but the individual is less likely to care about costs. For now, it is probably safe to say that most men are probably not being informed about the effects of the drug nor asked what they would like to do about it.

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