Abstract
First-line treatment options for patients with metastatic hormone-sensitive prostate cancer (HSPC) are divided into two groups: androgen receptor signaling inhibitor (ARSI)-based doublet therapy and triplet therapy (which includes chemotherapy in addition to doublet therapy). However, differences in therapeutic efficacy between the two groups remain unclear. The aim of the study was to perform a comparative analysis between the two groups and to identify predictors of treatment response. We retrospectively recruited 500 patients with mHSPC treated with doublet or triplet therapy from our hospital and affiliated hospitals between 2013 and 2025. The cohort of patients with mHSPC treated with doublet therapy received ABI, ENZ, or APA in combination with a luteinizing hormone-releasing hormone analog, such as androgen deprivation therapy (ADT). The cohort of those treated with triplet therapy received darolutamide plus ADT and docetaxel. Cox proportional hazards regression analysis was performed to identify prognostic factors of overall survival in patients with mHSPC. Propensity score matching was used to adjust the clinical background of patients. The outcome (prostate-specific antigen-progression-free survival, second progression-free survival, and overall survival (OS)) of triplet therapy was significantly better than that of doublet therapy in matched high-risk patients with mHSPC. Univariate and multivariate analyses of OS in matched patients with high-risk mHSPC treated with triplet or doublet therapy suggested that treatment choice (triplet or doublet), pretreatment LDH levels, and presence of Gleason pattern 5 influenced OS in patients with high-risk mHSPC. Subgroup analysis suggested that LDH levels and the presence of Gleason pattern 5 may be predictive factors of the treatment of patients with mHSPC. Our results showed that triplet therapy achieved a better outcome than doublet therapy in patients with mHSPC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-44627-w.