The effect of additional chemotherapy on high-risk prostate cancer: a systematic review and meta-analysis

OBJECTIVE: The role of additional chemotherapy in the treatment of high-risk prostate cancer (PCa) remains a controversy. This meta-analysis aimed to investigate the effect of additional chemotherapy on high-risk PCa. METHODS: Randomized controlled trials (RCTs) about additional chemotherapy for high-risk PCa were searched in PubMed, MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. We extracted HRs of overall survival (OS) and progression-free survival (PFS) for each trial and performed the meta-analysis using Review Manager 5.3. RESULTS: Eight RCTs involving 4,007 patients were included. Data from four trials, which could collect OS, showed that additional chemotherapy could not significantly improve the OS in patients with high-risk PCa (HR: 0.93; 95% CI: 0.79–1.09; P=0.37). However, the pooled analysis suggested significantly longer PFS in high-risk PCa patients treated with additional chemotherapy (HR: 0.81; 95% CI: 0.74–0.90; P<0.0001). The meta-analysis showed additional chemotherapy to androgen-deprivation therapy improved PFS (HR: 0.82; 95% CI: 0.74–0.91; P=0.0002). Greater improvement in PFS was found in high-risk PCa patients treated with additional docetaxel-based chemotherapy (HR: 0.73; 95% CI: 0.64–0.83; P<0.00001). No prolonged PFS was observed in high-risk PCa patients with non-docetaxel-based chemotherapy (HR: 0.97; 95% CI: 0.83–1.14; P=0.74). CONCLUSION: Additional chemotherapy, especially docetaxel-based chemotherapy, could significantly improve the PFS in high-risk PCa patients. More evidence about the effect of additional chemotherapy on OS is needed. Further investigations in PCa should also focus on the suitable population for chemotherapy as well as optimal use of chemotherapy.