5α-Reductase Inhibitors and Chemoprevention: The PCPT and Beyond

Prostate cancer chemoprevention holds the promise of significantly impacting a substantial public health concern. Large-scale, randomised data demonstrate that the type 2 5α-reductase inhibitor (5-ARI) finasteride can significantly lower the risk of prostate cancer when taken daily for a period of 7 yr. This reduction has been shown, with population modelling, to translate into a substantial reduction in prostate cancer cases. In addition, ageing men also benefit positively with regard to benign prostatic hyperplasia outcomes, and may also have a reduced likelihood of a diagnosis of prostatitis. From a risk perspective, the adverse events profile of finasteride in the Prostate Cancer Prevention Trial (PCPT) suggests that long-term use is not associated with significant tolerability concerns. The major finding of concern from the PCPT was the excess proportion of Gleason 7-10 tumours observed with finasteride treatment, but further analyses of the data demonstrate that the effects of 5-ARIs on both prostate volume, and to a lesser extent prostate-specific antigen levels, can result in increased detection rates, especially of high-grade disease. The risk-benefit profile of 5-ARIs therefore appears favourable when all the evidence is scrutinised. Further analyses from the PCPT, and the outcomes from the Reduction by Dutasteride of Prostate Cancer Events study with its higher-risk population, should determine whether available resources for chemoprevention of prostate cancer should be focussed to those at greatest risk, or a more widespread approach considered.