Comprehensive Evaluation of Androgen Receptor Pathway Inhibitors in Metastatic Castration-Sensitive Prostate Cancer: A Multicenter Inverse Probability of Treatment Weighting-Based Study

IF 2.4 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer Pub Date : 2025-12-01 Epub Date: 2025-09-16 DOI:10.1016/j.clgc.2025.102437

Keita Kobayashi , Takanori Tokunaga , Kazuhiro Nagao , Koki Fujikawa , Kazuo Oba , Kimio Takai , Hiroaki Matsumoto , Shigeru Sakano , Satoshi Shirataki , Yasuhide Tei , Masanori Tabara , Satoru Yoshihiro , Seiji Yano , Hideaki Ito , Seiji Kitahara , Chietaka Ohmi , Jumpei Akao , Koji Shiraishi

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Abstract

Introduction

Androgen receptor pathway inhibitor (ARPI) plus androgen deprivation therapy (ADT) is a guideline-endorsed standard for metastatic castration-sensitive prostate cancer (mCSPC). Robust comparative data on individual ARPIs and their subsequent management after castration resistance remain limited.

Methods

This multicenter retrospective study included consecutive patients who received first-line ARPI for mCSPC between January 2018 and December 2023. Inverse probability of treatment weighting (IPTW) balanced the baseline clinicopathological variables across the abiraterone (n = 136), enzalutamide (n = 80), and apalutamide (n = 58) cohorts. PSA response subgroups were defined as early response (PSA <0.2 ng/mL by 3 months and sustained for 12 months), delayed response (first attainment ≥6 months, sustained for 12 months), early relapse (attainment but rebound ≥0.2 ng/mL within 12 months), and nonresponse (no attainment).

Results

Among 274 evaluable male patients, apalutamide yielded more grade ≥2 toxicities and dose modifications, although grade ≥3 events were comparable across arms. After IPTW, time to castration-resistant prostate cancer (CRPC) and overall survival (OS) did not differ among the ARPIs (P = .657, P = .286), and PSA ≤0.2 ng/mL conversion rates at 1, 3, 6, and 12 months were similar. Patients with early and delayed responses showed equivalent times to CRPC, whereas patients with early relapse and nonresponse experienced a significantly shorter time to CRPC and OS (P < 0.001). Eighty-one patients developed CRPC; first-line docetaxel (n = 35) and ARPI (n = 26) achieved comparable OS (P = .849).

Conclusion

The efficacies of abiraterone, enzalutamide, and apalutamide were equivalent if the baseline imbalances were mitigated. Sustained PSA suppression <0.2 ng/mL for 12 months predicts favorable outcomes, regardless of the speed of decline, whereas failure to achieve or maintain this threshold is associated with poorer prognosis. The choice between docetaxel and alternative ARPI for first-line treatment of metastatic CRPC showed no survival differences.

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雄激素受体途径抑制剂在转移性去势敏感前列腺癌中的综合评价：一项基于治疗权重的多中心反概率研究。

简介：雄激素受体途径抑制剂（ARPI）加雄激素剥夺疗法（ADT）是转移性去势敏感前列腺癌（mCSPC）的标准治疗方法。关于个体arpi及其在去势抵抗后的后续处理的可靠比较数据仍然有限。方法：这项多中心回顾性研究纳入了2018年1月至2023年12月期间接受mCSPC一线ARPI治疗的连续患者。治疗加权逆概率（IPTW）平衡了阿比特龙（n = 136）、恩杂鲁胺（n = 80）和阿帕鲁胺（n = 58）队列的基线临床病理变量。PSA反应亚组被定义为早期反应(PSA结果：在274例可评估的男性患者中，阿帕鲁胺产生更多≥2级毒性和剂量改变，尽管≥3级事件在两组之间具有可比性。IPTW后，arpi之间发生去势抵抗性前列腺癌（CRPC）的时间和总生存期（OS）没有差异（P = 0.657, P = 0.286）， PSA≤0.2 ng/mL转化率在1、3、6和12个月相似。早期和延迟反应的患者到CRPC的时间相当，而早期复发和无反应的患者到CRPC和OS的时间明显更短（P < 0.001）。81例发生CRPC；一线多西他赛（n = 35）和ARPI （n = 26）获得了相当的OS （P = 0.849）。结论：如果基线失衡得到缓解，阿比特龙、恩杂鲁胺和阿帕鲁胺的疗效是相等的。持续的PSA抑制

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来源期刊

Clinical genitourinary cancer 医学-泌尿学与肾脏学

CiteScore

5.20

自引率

6.20%

发文量

201

审稿时长

54 days

期刊介绍： Clinical Genitourinary Cancer is a peer-reviewed journal that publishes original articles describing various aspects of clinical and translational research in genitourinary cancers. Clinical Genitourinary Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of genitourinary cancers. The main emphasis is on recent scientific developments in all areas related to genitourinary malignancies. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.