Gleason score and docetaxel response in advanced hormone-sensitive prostate cancer: The lower the better

Abstract

Aim: Recently, three randomized controlled trials evaluated the addition of docetaxel to ADT in advanced hormone-sensitive prostate cancer (aHSPC). Interestingly, all trials showed a trend towards improved OS in the subgroup of patients with Gleason <8 tumors. We herein performed a meta-analysis of these trials to assess the OS benefit of docetaxel in different Gleason score groups (<8 vs ≥8). Material and Method: We searched the Pubmed and Medline databases and ASCO conference proceedings (through February 1st 2018) for relevant trials. For each study, median OS values and hazard ratios (HR) with 95% confidence intervals (CI) collected across different Gleason score groups. We combined the HRs from each of the three eligible trials in the meta-analysis using the random-effect model. Results: Three eligible studies were included in the analyses (CHAARTED, GETUG-AFU-15, and STAMPEDE). In the meta-analysis of three studies, docetaxel-based chemotherapy plus ADT was associated with improved OS [HR: 0.74; 95% CI: 0.62-0.87; p<0.001]. Among patients with tumor Gleason score <8, addition of docetaxel to ADT significantly improved overall survival [HR: 0.66, 95% CI: 0.52–0.85, p=0.001]. Although there was a trend towards improved OS with docetaxel in patients with Gleason score of ≥8, the magnitude of risk reduction was lower and did not achieve statistical significance [HR: 0.81, 95% CI: 0.64–1.02, p=0.066]. Conclusion: In this meta-analysis, OS benefit with the addition of docetaxel to ADT was more prominent in Gleason score <8 tumors. We propose that Gleason score can be a useful criteria for treatment selection in patients with aHSPC. Keywords: Hormone-sensitive, prostate cancer, docetaxel, gleason score