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. 2025 Aug 19.
doi: 10.1111/iju.70197. Online ahead of print.

Prognostic Impact of Time to Castration Resistance on Overall Survival in Patients With Metastatic Castration-Sensitive Prostate Cancer

Hiroaki Iwamoto  1 , Tomohiro Hori  1 , Takahiro Inaba  1 , Ryunosuke Nakagawa  1 , Taiki Kamijima  1 , Hiroshi Kano  1 , Tomoyuki Makino  1 , Renato Naito  1 , Hiroshi Yaegashi  1 , Takahiro Nohara  1 , Kazuyoshi Shigehara  1 , Kouji Izumi  1 , Atsushi Mizokami  1
Affiliations

Prognostic Impact of Time to Castration Resistance on Overall Survival in Patients With Metastatic Castration-Sensitive Prostate Cancer

Hiroaki Iwamoto et al. Int J Urol. .

Abstract

Objectives: Treatment strategies for metastatic castration-sensitive prostate cancer (mCSPC) have advanced significantly, yet the prognostic impact of time to castration resistance (TTCR) on overall survival (OS) remains unclear. This retrospective study aimed to evaluate the relationship between TTCR and OS.

Methods: Among 218 patients diagnosed with pure prostatic adenocarcinoma and treated with combined androgen blockade therapy at Kanazawa University Hospital between 2000 and 2020, 160 who progressed to metastatic castration-resistant prostate cancer (mCRPC) were included. OS was evaluated from initial diagnosis (OS-PC) and from mCRPC progression (OS-CRPC). TTCR was stratified into four groups. Kaplan-Meier analysis and log-rank tests were used to assess survival. Outcomes were further analyzed based on the use of androgen receptor signaling inhibitors (ARSIs) post-mCRPC progression.

Results: The median follow-up was 50.1 months. Median OS-PC and OS-CRPC were 70.6 and 48.1 months, respectively. Shorter TTCR and Gleason pattern 5 were associated with worse OS-PC. ALP (IFCC) > 130 IU/L, LDH (IFCC) > 300 IU/L, and shorter TTCR predicted poorer OS-CRPC. Among patients with TTCR ≥ 12 months, ARSI use post-mCRPC progression was significantly associated with improved OS-PC and OS-CRPC. In contrast, for patients with TTCR < 12 months, ARSI treatment improved OS-CRPC but not OS-PC.

Conclusions: Short TTCR was linked to reduced OS-PC and OS-CRPC. ARSI therapy after mCRPC progression provided substantial survival benefits, particularly in patients with TTCR ≥ 12 months. These findings may help reconsider the role of CAB in Asians, including Japanese.

Keywords: androgen deprivation therapy; combined androgen blockade; metastatic castration‐sensitive prostate cancer; novel androgen receptor signaling inhibitor; overall survival; time to castration resistance.

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