Chemoprevention of prostate cancer in men with high-grade prostatic intraepithelial neoplasia (HGPIN): a systematic review and adjusted indirect treatment comparison

Background: High-grade prostatic intraepithelial neoplasia (HGPIN) is the precursor or premalignant form of prostate cancer. At least 30% patients with a confirmed HGPIN will develop prostate cancer within 1 year after repeated biopsy. HGPIN patients are the appropriate at-risk population for chemoprevention strategies investigation against prostate cancer. However the commonly used chemoprevention agents that targeted on hormonal imbalance or lifestyle-related factors showed varied results in HGPIN patients. Methods: Literature searches were conducted in PubMed, EMBASE and Cochrane library according to Cochrane guidelines before January 31(st), 2017. Direct metaanalysis were performed to summarize the efficacy of candidate chemopreventative agents Dutasteride, Flutamide, Toremifene, Selenium, Green tea components, Lycopene and natural food products combination. Adjusted indirect meta-analyses were employed to compare the relative efficacy of these candidate chemoprevention agents head-to-head. Results: The overall incidence of prostate cancer in HGPIN was slightly decreased by chemoprevention agents (25.7% vs 31.5%, RR = 0.92, 95% CI: 0.83-1.03, P = 0.183), with minor heterogeneity (I-2 = 22.3%,X-2=15.08, P = 0.237), but without statistical significance. Subgroup analysis showed that green tea catechins significantly decreased prostate cancer in HGPIN patients (7.60% vs 23.1%, RR = 0.39, 95% CI: 0.16-10.97, P P = 0.044), with moderate heterogeneity (I-2 = 47.9%,X-2 = 1.92, P = 0.166). The adjusted indirect meta-analysis favored green tea catechins over other chemoprevention agents, and significantly when compared to natural food products combination (RR = 0.355, 95% CI: 0.134-0.934). Conclusion: The overall efficacy of chemoprevention agents in HGPIN patients is limited. But Green tea catechins showed the superiority to decrease prostate cancer in HGPIN patients.