1. The use of 5α-reductase inhibitors (5ARIs) was not associated with increased risk of developing high-grade or lethal prostate cancer.
2. 5ARI use was associated with a decreased incidence of low-risk and overall prostate cancer.
Evidence Rating Level: 2 (Good)
Study Rundown: 5ARIs have previously been associated with a decreased incidence of prostate cancer in large randomized control trials; however, the same trials also demonstrated an increased risk of high-grade prostate cancer. The authors of this paper prospectively followed 38,058 men from 1996 to 2010 to further elucidate the relationship between 5ARI use and the incidence of high-grade prostate cancer. This study demonstrated that 5ARI use was not associated with an increased risk of high-grade (HR: 0.97; 95% CI:0.64-1.46) or lethal (HR: 0.99; 95% CI: 0.58-1.69) prostate cancer. Furthermore, no associations were found between duration of 5ARI use and the incidence of high-grade prostate cancer. This study also supports the results of previous randomized controlled trials that demonstrated that 5ARI use was associated with a significant decrease in the overall incidence of prostate cancer (HR: 0.77; 95%CI: 0.57-0.95). The strength of this study is the prospective design along with the long follow-up period, but all participants in this study were Caucasian males, which limit the generalizability of this result.
In-Depth [prospective study]: This prospective observational study followed 38,058 men from 1996 to 2010 as part of the Health Professionals Follow-up Study in Boston, Massachusetts. In 448,803 person-years of follow-up, there were 289 cases of lethal and 456 cases of high-grade (Gleeson score 8-10) prostate cancer. Use of 5ARIs was reported by 2878 (7.6%) participants. Cox proportional hazard models demonstrated no significant association between use of 5ARIs and high-grade or lethal prostate cancer (HR: 0.99; 95% CI: 0.58-1.69). No associations were detected when the definition of high-grade cancer were expanded to include Gleeson score 7 (HR: 1.07; 95% CI: 0.79-1.45). Increased duration of 5ARI use was significantly associated with a decrease in overall prostate cancer (HR for 1 additional year of use: 0.95; 95% CI: 0.92-0.99); however no association was found between duration of use and high-grade prostate cancer.
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