Abstract
The use of 5α-reductase inhibitors (5α-RIs) as prostate cancer chemoprevention agents is controversial. Two large randomized trials, the Prostate Cancer Prevention Trial (PCPT) and the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) Trial, have both shown a decreased incidence of prostate cancer in patients administered with 5α-RIs. Both studies showed, however, an increased risk of higher-grade prostate cancer. Numerous studies have since analyzed the inherent biases in these landmark studies and have used mathematical modeling to estimate the true incidence of prostate cancer and the risk for high-grade prostate cancer in patients undergoing 5α-RI treatment. All primary publications associated with the PCPT and REDUCE studies were reviewed in detail. Pertinent references from the above publications were assessed and a literature search of all published articles associated with PCPT, REDUCE or 5α-RIs as chemopreventative agents through October 2013 was performed using Pubmed/Medline. PCPT and REDUCE both showed a significant decrease in the incidence of prostate cancer following the administration of 5α-reductase inhibitor, as compared with placebo, suggesting that 5α-RIs may be effective agents for prostate cancer chemoprevention. Inherent biases in the design of these two studies may have caused an artificial increase in the number of high-grade cancers reported. Mathematical models, that integrated data from these trials, revealed neither an increased nor decreased risk of high-grade disease when taking these biases into consideration. Moderately strong evidence exists that 5α-RIs may reduce the risk of prostate cancer. PCPT and REDUCE showed a decreased prevalence of prostate cancer in patients taking 5α-RIs. Urologists should have a working knowledge of these studies and discuss with patients the risks and benefits of 5α-RI treatment. Further studies to evaluate the cost-effectiveness of chemoprevention with 5α-RIs and appropriate patient selection are warranted.
Highlights
The use of 5α‐reductase inhibitors (5α‐RIs) as prostate cancer chemoprevention agents is controversial
The results of Prostate Cancer Prevention Trial (PCPT) and Reduction by Dutasteride of Prostate Cancer Events (REDUCE) showed a significant reduction in the overall incidence of prostate cancer in patients administered with 5α‐RIs, but there was an increased incidence of high grade tumors in the treatment arm of both studies
Debates have revolved around the number of patients excluded from the final analysis of the PCPT, increased sensitivity and specificity of prostate cancer detection in biopsies on patients in the treatment arms of each study and inherent selection biases in both studies
Summary
Administered with 5α‐RIs, but there was an increased incidence of high grade tumors in the treatment arm of both studies. There was no significant increase, in the high‐grade cancer detected in the finasteride group as compared with the placebo (4.8 vs 4.2%, P=0.012) Another potential bias in these studies is the increased sensitivity and specificity of the prostate biopsy in the treatment arms of each study. These results showed no significant differences in prostate cancer mortality in these studies, with a trend towards an increased risk using the original PCPT date, and a trend towards decreased risk using the adjusted PCPT and REDUCE data These data were corroborated by a more recent updated analysis of patients from the PCPT, which showed no significant differences in overall survival between the placebo and treatment groups [27]. The estimation of prostate cancer prevalence showed a decreased risk of overall and high‐grade disease in the finasteride arm as compared with the placebo, resulting in a 27% relative risk reduction for high‐grade tumors (95% confidence interval, 0.56‐0.96; P=0.02) [19]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
