Real-World Experience with Triplet Therapy for High-Volume Metastatic Castration-Sensitive Prostate Cancer: A Retrospective Cohort Study from a Japanese Academic Hospital.

Background: Prostate cancer (PCa) significantly contributes to male cancer mortality. Triplet therapy shows promise for metastatic castration-sensitive prostate cancer (mCSPC), but real-world data are limited. This study aimed to evaluate the clinical outcomes of triplet therapy in real-world patients with mCSPC at an academic hospital in Japan.

Methods: We retrospectively analyzed the efficacy and safety of triplet therapy, comprising androgen deprivation therapy, docetaxel, and darolutamide, in patients with mCSPC at Nippon Medical School Hospital. Clinical outcomes, adverse events (AEs), prostate-specific antigen (PSA) responses, and progression to castration-resistant prostate cancer were assessed.

Results: Between January 2023 and June 2024, we identified 14 Japanese patients with mCSPC who received triplet therapy. All patients presented with synchronous high-volume metastases as defined by the CHAARTED criteria. The median follow-up period was 7.9 months. In terms of efficacy, all 14 patients achieved PSA reduction of > 90%, while 13 of them achieved reductions of > 99%. AEs were reported in all patients, with grade 3 or higher AEs occurring in 10 patients. One patient permanently discontinued treatment and 4 patients temporarily interrupted therapy due to AEs. During follow-up, biochemical progression was observed in 2 patients and radiological progression in 2 patients. Subsequent therapies were selected based on each patient's clinicopathological and genetic characteristics, with considerable variability in treatment approaches following progression.

Conclusions: While PSA responses were favorable and tolerability was generally high, progression patterns and subsequent therapies varied widely, highlighting the need for close monitoring and individualized treatment in patients with mCSPC receiving triplet therapy.