Efficacy, safety, and cost-effectiveness of reduced vs. full initial dose androgen receptor signaling inhibitors in non-metastatic castration-resistant prostate cancer: A multicenter retrospective study.

371 Background: The introduction of novel androgen receptor signaling inhibitors (ARSIs) has significantly transformed the systemic treatment landscape for non-metastatic castration-resistant prostate cancer (nmCRPC). However, ARSI therapy is associated with substantial adverse events (AEs) and increased medical costs. Dose reduction may offer a strategy to mitigate AEs and reduce costs, yet the efficacy, safety, and cost-effectiveness of reduced-dose ARSIs in nmCRPC remain unclear. Methods: This multicenter retrospective study included 251 patients with nmCRPC who received ARSI therapy. Patients were categorized into two groups based on the initial ARSI dose: reduced-dose group (n = 46) and full-dose group (n = 205). Prostate-specific antigen progression-free survival (PSA-PFS) and metastasis-free survival (MFS) were compared between groups. Monthly medical costs for first ARSI treatment were also evaluated. Results: The median age at nmCRPC diagnosis was 77 years, with a median follow-up of 46 months. The rates of any PSA response, PSA decline ≥50%, and PSA decline ≥90% were comparable between the full-dose and reduced-dose groups (85% vs. 89%, P = 0.640; 74% vs. 76%, P = 0.785; 46% vs. 35%, P = 0.171, respectively). No significant differences were observed in PSA-PFS ( P = 0.307) or MFS ( P = 0.199) between the groups. After adjusting for confounding variables, reduced initial dose ARSI use was not significantly associated with shorter MFS ( P = 0.984; hazard ratio: 0.992; 95% confidence interval: 0.467–2.107). The incidence of any-grade AEs and grade ≥3 AEs did not differ significantly between the groups (33% vs. 24%, P = 0.171; 3.9% vs. 4.3%, P = 1.000). Monthly medication costs for first ARSI treatment were significantly lower in the reduced-dose group compared to the full-dose group ($998 vs. $1,644, P < 0.001), representing an approximate 40% cost reduction. Conclusions: Reduced-dose ARSI therapy demonstrated comparable efficacy and safety to full-dose treatment in patients with nmCRPC, while significantly lowering medication costs. Dose reduction may be a viable strategy to enhance cost-effectiveness without compromising clinical outcomes.