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

// Kang Cui 1,* , Xiangnan Li 2,* , Yabing Du 1,* , Xiance Tang 3 , Seiji Arai 4,5 , Yiwei Geng 1 , Ying Xi 1 , Han Xu 6 , Yue Zhou 7 , Wang Ma 1 and Tengfei Zhang 1 1 Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China 2 Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China 3 Department of Medical Affairs, Henan Cancer Hospital, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China 4 Department of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States 5 Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Japan 6 Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China 7 Deparmtent of B-Ultrasound, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China * These authors have contributed equally to this work Correspondence to: Tengfei Zhang, email: // Wang Ma, email: // Keywords : HGPIN, prostate cancer, chemoprevention, adjusted indirect meta-analysis, green tea catechins Received : February 12, 2017 Accepted : March 06, 2017 Published : March 15, 2017 Abstract 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 meta-analysis 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%, 𝟀 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%, 𝟀 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.