Efficacy and safety of darolutamide plus androgen deprivation therapy in de novo metastatic hormone-sensitive prostate cancer: A single-center retrospective study.

e17085 Background: ADT alone provides limited benefit in mHSPC, with most patients progressing to castration resistance. Darolutamide combined with ADT is a promising non-chemotherapy option. Real-world data in Chinese patients remain scarce. This study aimed to evaluate the efficacy and safety of darolutamide plus ADT in a real-world mHSPC cohort. Methods: This single-center retrospective study included 78 de novo mHSPC patients treated at Tianjin Cancer Hospital, with enrollment between January 29, 2024, and June 11, 2025. Darolutamide was initiated at a reduced dose (half of the full dose) for the first two weeks, and then escalated to the full recommended dose of 600 mg. For ADT treatment, goserelin microspheres, 3.6mg, every 28 days. The primary endpoint was PSA reduction at 6 months; secondary endpoints included PFS, time to CRPC, OS, and AEs. Results: Of the 78 patients, the median age was 71 years, and 91.0% had ECOG 0–1. 51 (65.4%) had a Gleason score (GS) of 6–8, and 27 (34.6%) had a score of 9–10. Visceral metastasis was present in 18 patients (23.1%), and bone metastasis in 47 patients (60.3%), 45 (57.7%) were low-volume and 33 (42.3%) were high-volume. The median baseline PSA was 46.77ng/ml. The median follow-up was 9.9 months (95%CI: 9.4–10.4). At 6 months, 98.7% of patients achieved a PSA reduction of ≥90%, and all had a reduction of ≥50%. PSA decreased to < 0.2 ng/ml in 65 patients (83.3%), with 43 (55.1%) with PSA < 0.02 ng/ml. Across subgroups defined by GS, visceral metastases, and tumor burden, all patients achieved PSA50, indicating consistent clinical benefit. However, the proportion achieving PSA < 0.2 ng/ml differed among subgroups: patients with GS 6–8 showed higher response rates than those with GS 9–10 (P < 0.05), and patients without visceral metastases achieved higher rates than those with visceral metastases (88.3% vs. 66.7%, P < 0.05). No significant difference was observed between high and low tumor burden groups. As of the cut-off date(June 11, 2025), 75 patients (96.2%) remained on treatment. Data for survival endpoints are immature at this time. AEs occurred in 24 patients (30.8%), with the most common being fatigue (11.5%) and hot flashes (10.3%). One patient experienced a grade 3 AE (hypertension), while others had grade 1–2 AEs. No unexpected safety signals were observed, and AEs were manageable. Conclusions: This ongoing single-center, large-sample real-world study suggests that darolutamide plus ADT is an effective and well-tolerated treatment option for Chinese mHSPC patients. Both patients with and without visceral metastases derived clinical benefit, with those without visceral metastases showing more pronounced improvements. Continued follow-up is necessary to assess long-term efficacy and safety.