Triplet therapy with darolutamide and docetaxel for metastatic castration-sensitive prostate cancer: a multicenter real-world study

Abstract Background Triplet therapy with darolutamide and docetaxel has reshaped the treatment landscape of metastatic castration-sensitive prostate cancer (mCSPC). However, real-world evidence regarding its oncological outcomes and toxicity remains limited. Methods We retrospectively reviewed 112 consecutive patients with mCSPC who were treated with triplet therapy. A deep prostate-specific antigen (PSA) response was defined as a PSA level < 0.2 ng/ml or a ≥ 90% decline from baseline. Castration-resistant prostate cancer (CRPC)-free survival was used as the survival endpoint. Clinicopathological factors associated with CRPC-free survival were analysed using a Cox proportional hazards model. Treatment-related adverse events (AEs) were comprehensively documented by type and grade. Results During a median follow-up of 17.1 months, 15 patients developed CRPC and four died of prostate cancer; 1-year CRPC-free survival and overall survival rates were 89.8% (95% confidence interval, 83.9%–96.0%) and 98.8% (96.5%–100%), respectively. A deep PSA response was achieved in 73.2% of patients (PSA nadir <0.2 ng/ml) and in 96.4% (PSA ≥ 90% decline). In both the univariable and multivariable analyses, no baseline factor was significantly associated with CRPC-free survival. Grade ≥ 3 hematologic AEs occurred in 75.0% of patients. Among the 31 patients who discontinued docetaxel, 26 discontinued due to non-hematologic AEs. Conclusions Triplet therapy demonstrated substantial clinical activity in real-world patients with mCSPC, with high rates of deep PSA response despite frequent AEs. These findings support the feasibility of triplet therapy in routine practice. Given the substantial toxicity burden, careful patient selection and proactive AE management remain important.