Abstract
BACKGROUND: Metastatic hormone-sensitive prostate cancer (mHSPC) is an aggressive disease with a poor prognosis. Current treatment guidelines recommend combining androgen receptor axis-targeted therapies (ARATs) with androgen deprivation therapy (ADT) for mHSPC. While individual ARATs have shown success, few studies directly compare their effects. AIM: To compare the safety and clinical outcomes of abiraterone acetate (abiraterone) and apalutamide in chemotherapy-naïve mHSPC patients, focusing on prostate-specific antigen (PSA) kinetics, safety, and survival outcomes. METHOD: A retrospective, single-centre study included 107 chemotherapy-naïve mHSPC patients treated with abiraterone or apalutamide plus ADT. PSA levels were measured at baseline and during treatment. Primary outcomes were PSA progression-free survival (PSA-PFS) and overall survival (OS). Adverse events were recorded. Inverse probability treatment weighting adjusted baseline differences. RESULTS: Median PSA-PFS significantly favoured apalutamide (log-rank p = 0.015). Achieving PSA ≤ 0.02 ng/mL was strongly associated with delayed progression (HR 0.07, 95% CI 0.02-0.28; p < 0.001). OS did not differ significantly between groups (p = 0.504). Apalutamide achieved lower median nadir PSA (0.02 ng/mL vs. 0.23 ng/mL, p < 0.001) and shorter mean time to nadir (4.5 vs. 7.2 months, p = 0.001), with more patients reaching ultralow PSA levels (≤ 0.02 ng/mL) during follow-up. Adverse events occurred more frequently with apalutamide (71.2% vs. 46.5%, p = 0.015), with fatigue and rash being the most common. CONCLUSION: Apalutamide demonstrated deeper and more sustained PSA reductions, translating into delayed disease progression compared to abiraterone. Both treatments were generally well tolerated, though adverse events were more prevalent with apalutamide.