Department of Urology, Hamamatsu University Hospital, Shizuoka, Japan.
Department of Urology, Chutoen General Medical Center, Shizuoka, Japan.
Eur Urol Oncol. 2024 Jun;7(3):625-632. doi: 10.1016/j.euo.2023.12.013. Epub 2024 Jan 30.
Androgen deprivation therapy (ADT), administered alone, as combined androgen blockade (CAB) or as ADT plus androgen receptor signalling inhibitors (ARSIs) or ADT plus docetaxel, is the standard treatment for metastatic hormone-naïve prostate cancer (mHNPC) in Japanese real-world practice.
To investigate treatment patterns and clinical outcomes in LATITUDE criteria high-risk mHNPC.
DESIGN, SETTING, AND PARTICIPANTS: The longitudinal, multicentre, J-ROCK registry study enrolled patients initiating ADT in Japan after May 2019, and categorised them as cohort 1 (ADT or CAB) or cohort 2 (ADT plus ARSIs or docetaxel).
Prostate-specific antigen (PSA) response, progression-free survival (PFS), time to castrate-resistant prostate cancer (CRPC), overall survival (OS), and safety were evaluated. PFS, time to CRPC, and OS were estimated via the Kaplan-Meier method and between-cohort comparisons via multivariate Cox regression models.
In total, 974 patients were included (cohort 1: 38.1%, cohort 2: 61.9%). CAB was preferred (67.4%) to ADT alone in cohort 1, and abiraterone acetate plus prednisolone was used most frequently in cohort 2 (59.4%). The proportion of patients with ≥50%/≥90% PSA decline or who achieved PSA ≤0.2/≤0.1 ng/ml tended to be higher in cohort 2. PFS (adjusted hazard ratio 0.42; 95% confidence interval [CI] 0.31-0.55), time to CRPC (0.28; 95% CI 0.23-0.36), and OS (0.54; 95% CI 0.35-0.82) were longer in cohort 2. In cohorts 1 and 2, adverse drug reactions of special interest (ADRSIs) occurred in 1.3% and 15.1%, and fatal adverse events occurred in 1.9% and 1.7%, respectively. Limitations included nonrandomised design, varying time since marketing authorisation for ARSIs, and limited safety assessments.
ADT plus ARSIs or docetaxel was used more frequently to treat high-risk mHNPC than standard ADT/CAB and was associated with more favourable clinical outcomes. Although ADRSIs were reported more in cohort 2, the safety profile was considered tolerable.
Although many treatment options are available for high-risk metastatic prostate cancer, there are limited reports on real-world clinical experience with different therapies outside of the clinical trial setting. In this study, we compared clinical and safety outcomes with different treatment regimens, using a large series of patients with high-risk metastatic hormone-naïve prostate cancer across Japan. We found that androgen deprivation therapy in combination with newer androgen receptor signalling inhibitors resulted in improved response compared with androgen deprivation therapy alone or in combination with a first-generation antiandrogen.
雄激素剥夺疗法（ADT）单独使用、联合雄激素阻断（CAB）或 ADT 加雄激素受体信号抑制剂（ARSIs）或 ADT 加多西他赛，是日本真实世界实践中治疗转移性去势敏感型前列腺癌（mHNPC）的标准治疗方法。
研究 LATITUDE 标准高危 mHNPC 的治疗模式和临床结局。
设计、地点和参与者：这项纵向、多中心的 J-ROCK 登记研究纳入了 2019 年 5 月后在日本开始 ADT 的患者，并将他们分为队列 1（ADT 或 CAB）或队列 2（ADT 加 ARSIs 或多西他赛）。
评估前列腺特异性抗原（PSA）反应、无进展生存期（PFS）、去势抵抗性前列腺癌（CRPC）时间、总生存期（OS）和安全性。通过 Kaplan-Meier 方法估计 PFS、CRPC 时间和 OS，并通过多变量 Cox 回归模型进行队列间比较。
共纳入 974 例患者（队列 1：38.1%，队列 2：61.9%）。在队列 1 中，CAB 比 ADT 单独使用更受欢迎（67.4%），而在队列 2 中，阿比特龙联合泼尼松最常用（59.4%）。队列 2 中≥50%/≥90% PSA 下降或 PSA≤0.2/≤0.1ng/ml 的患者比例较高。队列 2 的 PFS（调整后的危险比 0.42；95%置信区间[CI]0.31-0.55）、CRPC 时间（0.28；95%CI0.23-0.36）和 OS（0.54；95%CI0.35-0.82）更长。在队列 1 和 2 中，分别有 1.3%和 15.1%发生药物不良反应（ADRIs），1.9%和 1.7%发生致命不良事件。局限性包括非随机设计、ARSIs 的上市时间不同以及安全性评估有限。
与标准 ADT/CAB 相比，ADT 加 ARSIs 或多西他赛更常用于治疗高危 mHNPC，且与更有利的临床结局相关。尽管队列 2 中报告了更多的 ADRSIs，但安全性被认为是可耐受的。
尽管有许多治疗选择可用于高危转移性前列腺癌，但在临床试验之外，关于不同治疗方案的真实世界临床经验的报告有限。在这项研究中，我们使用来自日本各地的大量高危转移性去势敏感型前列腺癌患者，比较了不同治疗方案的临床和安全性结局。我们发现，与 ADT 单独使用或与第一代抗雄激素联合使用相比，ADT 联合新型雄激素受体信号抑制剂可改善反应。
