Uchimoto Taizo, Iwatsuki Kengo, Komura Kazumasa, Fukuokaya Wataru, Adachi Takahiro, Hirasawa Yosuke, Hashimoto Takeshi, Yoshizawa Atsuhiko, Saruta Masanobu, Fujimoto Saizo, Minami Takafumi, Yamamoto Yutaka, Yamazaki Shogo, Takai Tomoaki, Sakamoto Moritoshi, Nakajima Yuki, Nishimura Kazuki, Maenosono Ryoichi, Tsujino Takuya, Nakamura Ko, Fukushima Tatsuo, Nishio Kyosuke, Yoshikawa Yuki, Yamamoto Shutaro, Iwatani Kosuke, Urabe Fumihiko, Mori Keiichiro, Yanagisawa Takafumi, Tsuduki Shunsuke, Takahara Kiyoshi, Inamoto Teruo, Fujita Kazutoshi, Kimura Takahiro, Ohno Yoshio, Shiroki Ryoichi, Azuma Haruhito
Department of Urology, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-Machi, Takatsuki City, Osaka, 569-8686, Japan.
Department of Urology, The Jikei University School of Medicine, 3-25-8, Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, Japan.
Int J Clin Oncol. 2025 Jan;30(1):123-133. doi: 10.1007/s10147-024-02649-2. Epub 2024 Oct 28.
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.
Data from the ULTRA-Japan study cohort from five academic institutes (496 mHSPC patients) were retrospectively analyzed.
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.
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.
雄激素受体信号抑制剂（ARSIs）成为转移性激素敏感性前列腺癌（mHSPC）的新治疗标准。在一线使用ARSIs时，去势抵抗时间（TTCR）是否具有预测价值尚不清楚。我们试图评估以TTCR为重点的一线ARSIs治疗的mHSPC患者的临床结局。
对来自五个学术机构的ULTRA-日本研究队列（496例mHSPC患者）的数据进行回顾性分析。
整个队列的中位总生存期（OS）为80个月，中位随访时间为18个月。496例患者中，分别有332例（67%）、82例（16.5%）和82例（16.5%）接受了一线醋酸阿比特龙+泼尼松、恩杂鲁胺和阿帕他胺治疗。在随访期间，共有155例（31%）被诊断为mCRPC，中位TTCR为10个月。在这155例患者中，TTCR>12个月是一线ARSIs治疗后OS更长的独立预测因素。对496例mHSPC患者启动一线ARSIs后的TTCR进行Cox回归分析，发现三个变量是TTCR缩短的独立预测因素，包括 Gleason评分（GS）≥9、疾病范围（EOD）≥2和肝转移的存在。
我们的结果表明，具有这三个特征的mHSPC患者可能对一线ARSIs（双联疗法）产生原发性耐药，因此需要考虑其他选择，如最近的三联疗法。
