Do disease status and race affect the efficacy of zoledronic acid in patients with prostate cancer? A systematic review and meta-analysis of randomized control trials

Abstract

Background Zoledronic acid (ZA) does not improve the overall survival (OS) of metastatic castration-resistant prostate cancer (mCRPC); however, little is known about the efficacy of ZA in to hormone-sensitive prostate cancer (HSPC), metastatic hormone-sensitive prostate cancer (mHSPC), and non- metastatic castration-resistant prostate cancer (nmCRPC). Therefore, we assessed the efficacy of ZA in patients with prostate cancer (PCa) and different disease statuses. Methods Fifteen eligible randomized-control trials (RCTs) with ZA intervention, including 8280 participants with HSPC, mHSPC, nmCRPC, and mCRPC, were analyzed. The primary and secondary outcome were overall survival(OS), and skeletal-related events (SREs), and bone mineral density (BMD). Results The participants included 8280 men (7856 non-Asian and 424 Asian). Seven trials yielded a pooled hazard ratio (HR) of 0.95 (0.88, 1.03; P = 0.19) for OS. Subgroup analysis revealed no significant improvement in OS in the HSPC, castration-resistant prostate cancer (CRPC), M0 and M1(bone metastasis) groups, with pooled HR (95%CI) of 0.96 (0.88,1.05), 0.78 (0.46,1.33), 0.95 (0.81,1.13), 0.85 (0.69,1.04) respectively. The Asian group exhibited improved in OS with an HR of 0.67 (0.48, 0.95; P = 0.02), whereas the non-Asian group showed no improvement in OS with an HR of 0.97 (0.90, 1.06; P = 0.52). Five trials yielded pooled odds ratio (OR) of 0.65 (0.45, 0.95; P = 0.02) for SREs. In the subgroup, SREs were significantly decreased in the M1 and Asian groups with ORs of 0.65 (0.45, 0.95; P = 0.02) and 0.42 (0.24, 0.71; P = 0.001), respectively. Six trials yielded a pooled mean difference (MD) of 8.08 (5.79, 10.37; P < 0.001) for BMD. In the HSPC we observed a stable improvement in increased BMD percentage with an MD (95%CI) of 6.65 (5.67, 7.62) (P = 0.001). Conclusions ZA intervention does not significantly improve OS in patients with prostate cancer (HSPC, CRPC, M0, M1) but probably improves OS in the Asian populations. M1 and Asian groups had exhibit a significant reduction in SREs regardless of the HSPC or CRPC status after ZA administration. Moreover, ZA treatment increases BMD percentage.