Screening for Predictive Factors of Efficacy of Second‐Generation Androgen Receptor Axis‐Targeted Agents in Patients With High‐Risk Metastatic Hormone‐Sensitive Prostate Cancer

ABSTRACT Background Differences in the effectiveness of second‐generation androgen receptor axis‐targeted agents (ARATs) in high‐risk metastatic hormone‐sensitive prostate cancer (mHSPC) remain unclear. This study aimed to identify the factors influencing the efficacy of ARATs in patients with high‐risk mHSPC and compare their long‐term effectiveness. Methods Four hundred and sixty‐six patients with mHSPC treated with ARATs were retrospectively recruited from our hospital and affiliated hospitals of the Kindai Oncology Study Group and Kyoto Prefectural University of Medicine Oncology Study Group between December 2013 and March 2024. Cox proportional hazards analysis was performed to identify prognostic factors for overall survival in patients with mHSPC. Propensity score matching was used to adjust for the differences in clinical backgrounds of the patients. Results Univariate and multivariable analyses revealed that Gleason pattern 5 and pretreatment ALP levels were notable prognostic factors for overall survival in patients with mHSPC treated with ARATs. In the subgroup of patients with high‐risk mHSPC with Gleason pattern 5, apalutamide and enzalutamide showed significantly better outcomes in terms of PSA‐PFS, PFS2, and overall survival compared to abiraterone acetate though selection bias and the small number of patients may be associated with the results in this study. Univariate and multivariable analyses suggested that ARATs selection (ABI vs. APA or ENZ) may serve as an independent predictor of overall survival in patients with high‐risk mHSPC with Gleason pattern 5 treated with ARATs. Conclusion Gleason pattern 5 may be a predictive factor for ARAT efficacy in patients with high‐risk mHSPCs.