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

期刊论文
发表日期：

2024年10月28日

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

摘要

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.