The case for prostate cancer risk reduction by 5-alpha reductase inhibitors

Prostate cancer remains a significant public health problem. The current approach with prostate-specific antigen (PSA)-based screening has questionable effects on prostate cancer-specific mortality but is clearly associated with overdiagnosis of prostate cancer, especially relatively low-risk and low-volume tumors. Methods to decrease overdiagnosis include alterations in screening practices and, potentially, the use of 5-alpha reductase inhibitors. This article reviews the major trials that have evaluated 5-alpha reductase inhibitors in this setting: the Prostate Cancer Prevention Trial (PCPT) and the Reduction by Dutasteride Prostate Cancer Events Trial (REDUCE). Although these trials enrolled different patient populations, their findings are complementary and suggest a potential role for these agents in prostate cancer risk reduction. Use of 5-alpha reductase inhibitors results in an approximate 25% reduction in the detection of prostate cancer, reduces diagnosis of high-grade prostatic intraepithelial neoplasia (PIN), and improves benign prostatic hyperplasia (BPH)-related outcomes and the performance of PSA as a diagnostic test for aggressive prostate cancer. Side effects occur in a small percentage of men and consist of decreased sexual function and libido as well as gynecomastia. The risk of high-grade tumor development while receiving these agents is uncertain.