5-Alpha Reductase Inhibitors in Prostate Cancer

TLDR: The authors question the validity of a basic assumption of the study, namely, that rising PSA after radical therapy is indicative of recurrent or residual PCa, and expand on a number of points raised in the editorial.

Abstract: We agree with the introductory comments in the editorial by Ehdaie and Touijer [1]. Our understanding of the role of endocrine factors, such as androgen synthesis, in the tissue of castration-resistant prostate cancer (PCa) has improved rapidly and may result in more effective ways of interacting with the androgen receptor with the promise of rapid clinical application. We also agree that despite availability of data from several randomized controlled trials [2–4] ,p rogress with respect to the application of 5-alpha reductase inhibitors (5-ARIs) for PCa prevention has been less convincing. However, the finding of rising prostate-specific antigen (PSA) after potentially curative management of PCa is one of the conditions with which clinicians are most frequently confronted, and no first-line evidence-based treatment is available. We are therefore confronted with a difficult question: How much uncertainty around treatment decisions is acceptable in a situation of ignorance of the best management of proven minimal PCa progression? We would like to expand on a number of points raised in the editorial [1]. The authors question the validity of a basic assumption of our study [5], namely, that rising PSA after radical therapy is indicative of recurrent or residual PCa. They argue that the effect on PSA doubling time seen in our study may be in part due to ‘‘PSA changes in benign prostatic tissue,’’ presumably left behind after radiotherapy (RT) or radical prostatectomy (RP). Although this possibility cannot be entirely excluded, our data do not support it. Residual benign prostatic tissue left behind at RP is an extremely rare event in the hands of any surgeon; after RT, benign PSA-producing tissue always remains. Data from the REDUCE study showed stability of PSA values over a 2-yr period in 2566 men treated with placebo and without a