Real-World Clinical Outcomes of Darolutamide in Older Patients With Non-metastatic Castration-Resistant Prostate Cancer: A Multi-institutional Comparative Analysis of Efficacy and Tolerability.

Background There is still a lack of real-world data comparing clinical use of darolutamide, oncological outcomes, and safety profiles among older patients. We aimed to evaluate the real-world clinical outcomes of darolutamide in older patients with non-metastatic castration-resistant prostate cancer (nmCRPC) by comparing efficacy and tolerability across different age groups. Methods We retrospectively analyzed 36 patients with nmCRPC who received darolutamide at nine institutions. Patients were stratified into two age-based subgroups: ≥75 vs. <75 years and ≥80 vs. <80 years. Primary outcomes were oncological, including prostate-specific antigen (PSA) response (50% or 90% decline), progression-free survival (PFS), and overall survival (OS). Secondary outcomes included safety, adverse events (AEs), and rates of treatment interruption, discontinuation, and dose reduction. Results Twenty-five patients (69.4%) were aged ≥75 years, and 13 patients (36.1%) were aged ≥80 years. The overall PSA response rates were 88.9% for a 50% decline and 69.4% for a 90% decline. PSA response did not differ between age groups for either 75- or 80-year thresholds. No significant differences were observed in PFS or OS between subgroups. The incidence of all-grade and grade ≥3 AEs was comparable across age groups. However, patients aged ≥80 years showed significantly higher rates of dose reduction or treatment interruption (P = 0.016). Conclusions Darolutamide demonstrated high PSA response rates and favorable survival outcomes in elderly patients with nmCRPC. Its effectiveness was consistent across age subgroups. While overall safety profiles were similar, patients aged ≥80 years were more likely to need dose adjustments or temporary treatment interruptions, supporting the use of this drug in this population.