Radiographic progression (RP) without prostate-specific antigen (PSA) elevation has emerged as a clinically important pattern in the androgen receptor pathway inhibitors (ARPI) era, but its prevalence and prognostic significance in real-world metastatic hormone-sensitive prostate cancer (mHSPC) cohorts remain unclear.
To assess the prevalence and prognostic implications of RP alone progression in mHSPC patients treated with first-line ARPIs.
We retrospectively analyzed 518 mHSPC patients treated with abiraterone acetate plus prednisolone, enzalutamide, or apalutamide. PSA progression was defined using PCWG3 criteria. Patients were categorized into PSA progression or RP alone progression groups, and clinical outcomes were compared.
Among 169 patients who developed castration-resistant prostate cancer (CRPC), 34 (20.1%) experienced RP alone. RP alone patients had significantly worse overall survival compared to those with PSA progression (median 21 vs. 39 months, p = 0.007), despite exhibiting deeper biochemical responses-PSA nadir (0.055 vs. 0.86 ng/mL, p < 0.001) and a higher rate of PSA nadir < 0.2 ng/mL (61.8% vs. 27.4%, p < 0.001). The baseline characteristic differing between groups was CHAARTED volume classification; high volume disease was markedly more common in RP alone patients (94.1% vs. 77.8%). In univariate and multivariate analyses of the overall cohort, CHAARTED high volume disease was identified as an independent risk factor for RP alone (HR 10.3, 95% CI 1.20-89.3; p = 0.034).
RP alone progression occurred in approximately one-fifth of patients and was associated with significantly poorer survival despite excellent PSA responses, underscoring the limitation of PSA-based monitoring and supporting routine imaging for early detection of PSA-incongruent disease progression in mHSPC.
The Prostate. 2026 Mar 15 [Epub ahead of print]
Takeshi Tsutsumi, Shogo Yamazaki, Takuya Matsuda, Takuya Tsujino, Taizo Uchimoto, Takafumi Yanagisawa, Keiichiro Mori, Wataru Fukuokaya, Masanobu Saruta, Atsuhiko Yoshizawa, Shingo Toyoda, Saizo Fujimoto, Kyosuke Nishio, Moritoshi Sakamoto, Tatsuo Fukushima, Ko Nakamura, Kazuki Nishimura, Keita Nakamori, Tomohisa Matsunaga, Yuki Yoshikawa, Ryoichi Maenosono, Kiyoshi Takahara, Teruo Inamoto, Takahiro Kimura, Kazutoshi Fujita, Kazumasa Komura, Haruhito Azuma
Department of Urology, Osaka Medical and Pharmaceutical University, Takatsuki City, Osaka, Japan., Department of Urology, The Jikei University School of Medicine, Tokyo, Japan., Department of Urology, Fujita-Health University School of Medicine, Toyoake City, Aichi, Japan., Department of Urology, Kindai University Faculty of Medicine, Sayama City, Osaka, Japan., Department of Urology, Kawasaki Medical School, Okayama, Japan., Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.