Comparison of prostate-specific antigen kinetics between androgen receptor signaling inhibitor doublet therapy and androgen receptor signaling inhibitor with docetaxel triplet therapy in patients with metastatic castration-sensitive prostate cancer.

159 Background: Doublet therapy consisting of androgen deprivation therapy (ADT) plus an androgen receptor signaling inhibitor (ARSI), or triplet therapy of ADT with docetaxel and ARSI, are recommended treatment options for metastatic castration-sensitive prostate cancer (mCSPC). However, real-world comparative data between these regimens are limited. This study aimed to compare prostate-specific antigen (PSA) kinetics between doublet and triplet therapy in patients with mCSPC. Methods: We retrospectively analyzed systemic treatment–naïve patients with mCSPC treated in Japan between 2018 and 2024 using a multi-institutional database. Patients received either doublet (ADT + ARSI) or triplet (ADT + docetaxel + ARSI) therapy. PSA nadir (≤0.02 ng/mL) and PSA response rates (≥90% and ≥99% decline from baseline at 3 months) were evaluated. Propensity score matching (2:1 ratio) was applied to adjust for baseline characteristics including age, disease volume, and visceral metastasis. Results: After matching 768 patients, 188 were included in the doublet and 94 in the triplet group. At 12 months, the proportion achieving PSA ≤ 0.02 ng/mL was significantly higher in the triplet group (p < 0.05), particularly in those with high-volume disease. PSA response ≥ 99% at 3 months was comparable between groups (p = 0.08). In contrast, triplet therapy showed favorable PSA kinetics in low-volume disease (p < 0.05). Grade ≥ 3 treatment-related adverse events occurred more frequently with triplet therapy. Conclusions: Triplet therapy demonstrated deeper PSA declines in selected subgroups but was associated with higher toxicity. Treatment selection should consider disease volume, comorbidities, and patient tolerability. Clinical trial information: R04-250 .