The Predictive Role of the Gleason Score in Determining Prognosis to Systematic Treatment in Metastatic Castration-Sensitive Prostate Cancer

Background: Gleason scores of 8 or higher indicate a poorer prognosis in metastatic castration-sensitive prostate cancer (mCSPC). This study aims to perform a systematic review and network meta-analysis (NMA) to compare overall survival (OS) and progression-free survival (PFS) among combination therapies with androgen receptor signaling inhibitors (ARSIs) in mCSPC patients, stratified by Gleason score ≥8 and <8. Methods: A literature search was conducted across PubMed, Embase, and Web of Science, using a PRISMA-guided systematic search strategy, covering January 2013 to June 2024. Results: Twelve studies including 12,652 patients were included in the NMAs. In the overall population, most ARSI combination therapies improved survival outcomes, except for orteronel + androgen deprivation therapy (ADT). In the Gleason score ≥8 subgroup, all ARSI combination therapies improved OS, with rezvilutamide showing the highest probability of being the best treatment for OS (HR 0.48, 95% CI 0.31–0.76, P-scores 0.88). In the Gleason score <8 subgroup, only darolutamide + docetaxel + ADT (HR 0.49, 95% CI 0.29–0.81) and apalutamide + ADT (HR 0.67, 95% CI 0.46–0.98) improved OS. Conclusions: ARSI combination therapy is effective for mCSPC patients with Gleason score ≥8, but further investigation is needed to confirm its efficacy in patients with Gleason score <8.