BackgroundOptimal drug selection for metastatic hormone-sensitive prostate cancer (mHSPC) remains unclear. We therefore assessed the clinical outcomes of mHSPC treated with new-generation androgen receptor pathway inhibitors (ARSIs) and identified risk factors associated with the prognosis of mHSPC. MethodsWe retrospectively reviewed 324 patients with mHSPC who were treated with ARSIs, including abiraterone acetate, enzalutamide, and apalutamide, between January 2018 and December 2022. In addition to assessing the prostate-specific antigen (PSA) response and overall survival (OS) during ARSI treatment, we investigated several potential risk factors for a poor OS in patients with mHSPC. ResultsPatients with a ≥ 90% PSA reduction (hazard ratio [HR]: 0.24, 95% confidence interval [CI], 0.10-0.58; P = .002) and those whose PSA declined to ≤ 0.2 ng/mL (HR: 0.22, 95% CI, 0.08-0.63; P = .005) showed significantly better OS than other patients. Gleason grade group 5 (GG5), presence of liver metastasis, and an LDH ≥ 250 U/L were identified as prognostic factors significantly associated with a poor OS, with HRs of 2.31 (95% CI, 1.02-5.20; P = .044), 7.87 (95% CI, 2.61-23.8; P < .001) and 3.21 (95% CI, 1.43-7.23; P = .005). ConclusionWe identified GG5, the presence of liver metastasis, and elevated LDH at the diagnosis as significant factors predicting the OS of mHSPC, but the choice of ARSIs did not affect the prognosis. The potential prognostic impact of these markers requires further investigation.