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. 2025 Jan;30(1):123-133.
doi: 10.1007/s10147-024-02649-2. Epub 2024 Oct 28.

Predicting time to castration resistance with androgen-receptor signaling inhibitors in hormone-sensitive prostate cancer: data from ULTRA-Japan Consortium

Taizo Uchimoto #  1 , Kengo Iwatsuki #  1 , Kazumasa Komura  2 , Wataru Fukuokaya  3 , Takahiro Adachi  4 , Yosuke Hirasawa  4 , Takeshi Hashimoto  4 , Atsuhiko Yoshizawa  5 , Masanobu Saruta  5 , Saizo Fujimoto  6 , Takafumi Minami  6 , Yutaka Yamamoto  6 , Shogo Yamazaki  1 , Tomoaki Takai  1 , Moritoshi Sakamoto  1 , Yuki Nakajima  1 , Kazuki Nishimura  1 , Ryoichi Maenosono  1 , Takuya Tsujino  1 , Ko Nakamura  1 , Tatsuo Fukushima  1 , Kyosuke Nishio  1 , Yuki Yoshikawa  1 , Shutaro Yamamoto  3 , Kosuke Iwatani  3 , Fumihiko Urabe  3 , Keiichiro Mori  3 , Takafumi Yanagisawa  3 , Shunsuke Tsuduki  3 , Kiyoshi Takahara  5 , Teruo Inamoto  1 , Kazutoshi Fujita  6 , Takahiro Kimura  7 , Yoshio Ohno  4 , Ryoichi Shiroki  5 , Haruhito Azuma  1
Affiliations

Predicting time to castration resistance with androgen-receptor signaling inhibitors in hormone-sensitive prostate cancer: data from ULTRA-Japan Consortium

Taizo Uchimoto et al. Int J Clin Oncol. 2025 Jan.

Abstract

Background: Androgen-receptor signaling inhibitors (ARSIs) become the new standard of care for metastatic hormone-sensitive prostate cancer (mHSPC). It is unknown whether time to castration resistance (TTCR), when using the first-line ARSIs, offers predictive value in mHSPC. We sought to assess the clinical outcomes for mHSPC patients treated with first-line ARSIs focusing on the TTCR.

Methods: Data from the ULTRA-Japan study cohort from five academic institutes (496 mHSPC patients) were retrospectively analyzed.

Results: The median overall survival (OS) in the total cohort was 80 months with a median follow-up of 18 months. Of 496 patients, 332 (67%), 82 (16.5%), and 82 (16.5%) were treated with first-line abiraterone acetate + prednisone, enzalutamide, and apalutamide, respectively. During the follow-up, a total of 155 (31%) were diagnosed with mCRPC with a median TTCR of 10 months. In those 155 patients, TTCR > 12 months is an independent predictor of longer OS from the first-line ARSIs. Cox regression analysis of the TTCR from initiating first-line ARSI in 496 mHSPC patients revealed three variables as independent predictors of shorter TTCR, including Gleason's score (GS) ≥ 9, the extent of disease (EOD) ≥ 2, and the presence of liver metastasis.

Conclusion: Our results indicate that mHSPC patients with those three features are likely to have primary resistance to first-line ARSIs (doublet therapy), thus requiring consideration of other options, such as the recent triplet approach.

Keywords: Abiraterone acetate; Androgen-receptor signaling inhibitors; Apalutamide; Enzalutamide; Metastatic hormone-sensitive prostate cancer; Time to castration resistance.

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Conflict of interest statement

Declarations. Conflict of interest: Komura K has received honoraria from Astellas. Fujita K has received honoraria from Bristol Myers Squibb, Merck Sharp & Dohme (MSD), AstraZeneca, Takeda, Astellas, Janssen, Ono, and Ferring Pharmaceutical Co., Ltd. Kimura K has received honoraria from Astellas, AstraZeneca, Bayer, Janssen, Sanofi and Takeda Pharmaceutical Co., Ltd. Ethical approval: This article was approved by Institutional Review Board of Osaka Medical and Pharmaceutical University (approval number: RIN-750-2571, approved on 24th January 2020).

References

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