Efficacy, Safety, and Cost‐Effectiveness of Reduced versus Full Initial Doses of Androgen Receptor Signaling Inhibitors in Non‐Metastatic Castration‐Resistant Prostate Cancer: A Multicenter Retrospective Study

Background The introduction of novel androgen receptor signaling inhibitors (ARSIs) has substantially transformed the systemic treatment landscape for non‐metastatic castration‐resistant prostate cancer (nmCRPC). Unfortunately, ARSI therapy is associated with considerable adverse events (AEs) and high medical costs. Dose reduction has been proposed as a potential strategy to improve tolerability and reduce costs; however, the efficacy, safety, and cost‐effectiveness of reduced‐dose ARSIs in patients with nmCRPC remain unclear. Methods This multicenter retrospective study included 251 patients with nmCRPC who underwent ARSI therapy. Patients were categorized into reduced‐dose ( n = 46) and full‐dose ( n = 205) groups according to the initial ARSI dose. The prostate‐specific antigen progression‐free survival (PSA‐PFS), metastasis‐free survival (MFS), and overall survival (OS) were compared between the groups. AEs and monthly medical costs for the first ARSI treatment were also evaluated. Results No significant differences in PSA‐PFS, MFS, or OS were observed between the two groups ( p = 0.307, p = 0.199, and p = 0.287, respectively). Multivariable analysis showed that the initial ARSI dose was not significantly associated with MFS ( p = 0.984). The incidence rates of any‐grade and grade ≥ 3 AEs did not significantly differ between the two groups ( p = 0.171 and P = 1.000, respectively). In contrast, the median monthly cost of the first ARSI treatment was significantly lower in the reduced‐dose group than in the full‐dose group ($998 vs. $1644, p < 0.001). Conclusions Reduced‐dose ARSI therapy was associated with comparable oncological outcomes to full‐dose therapy in patients with nmCRPC, while suggesting potential cost savings. Dose reduction may be considered a treatment option in selected populations, such as elderly patients, who were predominant in our cohort.