Do 5α-Reductase Inhibitors Alter Prostate Cancer Detection and What Are the Implications?

The 5α-reductase inhibitors (5-ARIs) have a number of effects on benign, hyperplastic, and malignant prostate epithelium. The extent of these effects appears to differ significantly among patients, and on average, appears less than that observed with luteinising hormone-releasing hormone (LHRH) agonist therapy. Indeed, the “characteristic changes” observed for hormonal therapy may not be so specific after all, if such changes can also be observed in men not receiving 5-ARIs or hormonal therapy. Although prostate specimens derived from men receiving a 5-ARI need to be interpreted with care, currently little evidence supports the original contention that use of a 5-ARI can result in significant misinterpretation of Gleason grade in those with prostate cancer. Data from the Prostate Cancer Prevention Trial (PCPT) strongly suggest that the reduction in prostate volume combined with changes in the performance of prostate-specific antigen (PSA) observed with 5-ARI treatment results in an excess detection of tumours, especially high-grade lesions, compared with untreated men. The effects of 5-ARIs on PSA appear to improve the predictive value of PSA as a diagnostic test for prostate cancer, possibly by differential suppression of PSA derived from cancerous and noncancerous tissue. New analyses, under development, are seeking to examine how this increased detection affects the reduction in risk of prostate cancer observed with 5-ARI therapy during the 7 yr of the PCPT.