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

Background Doublet therapy of androgen deprivation therapy (ADT) with androgen receptor signaling inhibitor (ARSI) or triplet therapy of ADT with docetaxel and ARSI represent possible treatment options in patients with metastatic castration-sensitive prostate cancer (mCSCaP). However, real-world data comparing these 2 treatments are lacking. Our objective was to compare prostate-specific antigen (PSA) kinetics between doublet and triplet therapy in patients with mCSCaP. Methods We retrospectively analyzed systemic treatment-naïve mCSCaP patients treated in Japan between 2018 and 2024. The patients received either doublet or triplet therapy. PSA nadir (≤ 0.02 ng/ml) and PSA response rates (≥ 90%, ≥ 99% reduction from baseline at 3 months) were assessed. Propensity score matching (2:1 ratio) was used to balance patient characteristics. Results After matching 768 patients with mCSCaP, 188 patients were included in the doublet and 94 in the triplet therapy groups. At 12 months, the proportion of patients achieving PSA ≤ 0.02 ng/ml was significantly higher in the triplet group than in the doublet group (P ' 0.05), particularly among those with high-volume disease. PSA response ≥ 99% at 3 months was comparable between the 2 groups (P = 0.08). Treatment related adverse events (TRAEs) of grade ≥ 3 were more frequent with triplet therapy. Conclusions Triplet therapy may offer superior PSA decline in patients with high-volume disease, however, this benefit comes at the cost of increased toxicity. Treatment choice should consider disease volume and patient tolerability.