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?