Randomized trials previously reported a reduction in prostate cancer diagnoses in men taking 5-alpha reductase inhibitors (5-ARIs).20,21 However, it was recently estimated that treatment of 200 men with 5-ARIs would result in three fewer Gleason 6 and one additional Gleason 8 to 10 tumors,

leading the US Food and Drug Administration to rule against their use in chemoprevention.22 In one abstract, O’Brien and colleagues compared pathologic tumor features between men who were and were not taking 5ARIs prior to radical prostatectomy.23 In this clinical Inhibitors,research,lifescience,medical cohort, they observed that long-term 5-ARI use (> 3 years) was associated with greater odds of non-organconfined and high-grade disease in Inhibitors,research,lifescience,medical the prostatectomy specimen. Other researchers further evaluated the relationship between 5-ARI use and long-term survival outcomes. In an Pfizer Licensed Compound Library order abstract from Denmark, Kjellman and colleagues examined the rates of metastasis and disease-specific mortality in 5-ARI users.24 Specifically, they compared 199 men taking 5-ARIs to 613 men using alpha-blockers and 2806 men not taking either of these medications. Overall, 5-ARI users had a significantly increased risk of metastatic disease (odds ratio [OR] 1.14; 95% confidence interval [CI], 1.01–1.29), although the difference Inhibitors,research,lifescience,medical in prostate cancer

mortality did not reach statistical significance. Interestingly, alpha-blocker Inhibitors,research,lifescience,medical use

was associated with a significantly lower risk of both metastases (OR 0.89; 95% CI, 0.81–0.98) and disease-specific death (OR 0.78; 95% CI, 0.67–0.9). These results corroborate prior findings from the Finnish Prostate Cancer Screening Trial, in which 5-ARIs were associated with an increased risk and alphablockers with a decreased risk of high-grade prostate cancer.25 Statins represent another type of medication under investigation for a Inhibitors,research,lifescience,medical possible role in prostate cancer chemoprevention because of numerous epidemiologic studies suggesting a decreased risk of aggressive prostate cancer. Freedland and colleagues26 examined the association between statin use and biopsy findings in 6729 men from the Reduction of Dutasteride in Cancer Ketanserin Events (REDUCE) trial, of which 17.5% reported statin use. On multivariable analysis, there was no significant relationship between statin use with low-grade (P=.62) or high-grade (P=.34) prostate cancer detection on biopsy. A randomized study has not been performed to evaluate a role for statins for prostate cancer prevention. Nevertheless, these combined findings would suggest the need for ongoing active investigation into novel chemopreventive strategies. [Stacy Loeb, MD, Alan W.