Prognostic Impact of Initial Prostate-Specific Antigen in Metastatic Hormone-Sensitive Prostate Cancer Patients With Extensive Bone Metastases Under Androgen Receptor Signaling Inhibitor

Objectives: We evaluated the association between initial prostate-specific antigen (iPSA) levels and prognosis in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC) and extensive bone metastases treated with androgen receptor signaling inhibitors (ARSI). Subjects and Methods: This retrospective study included 276 de novo high-risk mHSPC patients with extensive bone metastases (extent of disease [EOD] score ≥ 2) who received ARSI as first-line therapy. The data were collected from institutions participating in the ULTRA Japan Study group. Patient data were collected from institutions affiliated with the ULTRAJ group. Patients were stratified into quartiles based on iPSA levels, and a cutoff value of 200 ng/mL was used for subgroup analysis. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan–Meier curves and Cox proportional hazards regression models. A restricted cubic spline analysis was conducted to evaluate the nonlinear association between iPSA levels and OS. Results: Kaplan–Meier analysis demonstrated significant associations between iPSA quartiles and OS (p = 0.030), with the lowest survival observed in the lowest iPSA group (Q1: < 200 ng/mL). A spline-based analysis suggested an inverted J-shaped association between iPSA and OS, with the lowest hazard ratio observed at 1664 ng/mL. Patients with iPSA < 200 ng/mL exhibited significantly shorter OS than those with higher levels (p = 0.015), while no significant difference in PFS was observed (p = 0.869). Conclusions: Initial PSA levels were associated with prognosis in high-risk mHSPC with extensive bone metastases. Although patients with relatively low iPSA had significantly shorter OS, those exhibited no significant difference in PFS, suggesting that patients with low iPSA could benefit from ARSI as the 1st line treatment.