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

• Published in: The Prostate Vol. 85; no. 14; pp. 1307 - 1314
• Main Authors: Fujimoto, Saizo, Morita, Tsuyoshi, Yamamoto, Yutaka, Saruta, Masanobu, Yoshizawa, Atsuhiko, Takahara, Kiyoshi, Tsujino, Takuya, Maenosono, Ryoichi, Yoshikawa, Yuki, Fukuokaya, Wataru, Yanagisawa, Takafumi, Kimura, Takahiro, Hashimoto, Takeshi, Hirasawa, Yosuke, Ohno, Yoshio, Fujita, Kazutoshi
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.10.2025
• Subjects: Aged; Aged, 80 and over; Androgen Antagonists - therapeutic use; Androgen Receptor Antagonists - therapeutic use; androgen receptor signaling inhibitor (ARSI); Androgen receptors; Androgens; Antigens; Bone cancer; bone metastases; Bone Neoplasms - blood; Bone Neoplasms - drug therapy; Bone Neoplasms - secondary; high‐risk metastatic prostate cancer; Humans; initial prostate‐specific antigen (initial PSA); Male; Medical prognosis; Metastases; Metastasis; metastatic hormone‐sensitive prostate cancer (mHSPC); Middle Aged; Prognosis; Progression-Free Survival; Prostate cancer; Prostate-Specific Antigen - blood; prostate‐specific antigen (PSA); Prostatic Neoplasms - blood; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - mortality; Prostatic Neoplasms - pathology; Receptors, Androgen - metabolism; Regression analysis; Retrospective Studies; Survival; ULTRA Japan study; metastatic hormone‐sensitive prostate cancer (mHSPC); prostate‐specific antigen (PSA); androgen receptor signaling inhibitor (ARSI); prostate cancer; high‐risk metastatic prostate cancer; ULTRA Japan study; bone metastases; initial prostate‐specific antigen (initial PSA)
• ISSN: 0270-4137; 1097-0045; 1097-0045
• DOI: 10.1002/pros.70017

ABSTRACT 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.