Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Department of Urology, The Jikei University School of Medicine, Tokyo.
Curr Opin Urol. 2023 May 1;33(3):219-229. doi: 10.1097/MOU.0000000000001080. Epub 2023 Jan 24.
The landscape of therapy for metastatic castration-resistant prostate cancer (mCRPC) has seen an unprecedented transformation with the emergence of combination therapies. This review summarizes the current findings from randomized controlled trials (RCTs) assessing the oncologic outcomes of mCRPC.
In the first-line, treatment-naïve setting, recent RCTs demonstrated the oncologic benefit of adding AKT inhibitors or poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors to abiraterone in terms of radiographical progression-free survival. Although this is a strong surrogate endpoint, these agents have not yet shown overall survival (OS) improvement. In the second- or later-line settings, olaparib improved OS in patients with at least one alteration in BRCA1 , BRCA2 , or ATM gene and lutetium-177-prostate-specific membrane antigen-617 [177-Lu-prostate-specific membrane antigen (PSMA)-617] were superior to repeat androgen receptor signaling inhibitor (ARSI) therapy. In addition, 177-Lu-PSMA-617 had better progression-free survival compared with cabazitaxel but failed to result in an OS benefit. To date, there is no evidence for effective immune checkpoint inhibitor regimens/combinations for mCRPC.
According to recent RCTs, several novel agents and/or combinations exhibit promising oncologic outcomes. In the first-line setting, OS benefits compared with currently available regimens are still missing. Results from ongoing/well-designed phase 3 RCTs and real-world data regarding the sequential impact of currently available agents on outcomes of mCRPC patients after ARSI-based combination therapy for metastatic hormone-sensitive prostate cancer are awaited. Such data will improve clinical decision-making in the ever-intensifying treatment era.
转移性去势抵抗性前列腺癌（mCRPC）的治疗格局随着联合治疗的出现发生了前所未有的转变。本文综述了评估 mCRPC 肿瘤学结局的随机对照试验（RCT）的最新发现。
在一线、初治患者中，最近的 RCT 表明，在影像学无进展生存期方面，与阿比特龙相比，添加 AKT 抑制剂或聚（腺苷二磷酸核糖）聚合酶（PARP）抑制剂可带来肿瘤学获益。虽然这是一个强有力的替代终点，但这些药物尚未显示出总生存期（OS）的改善。在二线或更后的治疗线中，奥拉帕利改善了至少有 BRCA1、BRCA2 或 ATM 基因突变的患者的 OS，而镥-177-前列腺特异性膜抗原-617 [177-Lu-前列腺特异性膜抗原（PSMA）-617]优于重复雄激素受体信号抑制剂（ARSI）治疗。此外，177-Lu-PSMA-617 与卡巴他赛相比具有更好的无进展生存期，但未能带来 OS 获益。迄今为止，mCRPC 尚无有效的免疫检查点抑制剂方案/联合治疗的证据。
根据最近的 RCT，一些新的药物和/或联合治疗方案显示出有希望的肿瘤学结果。在一线治疗中，与现有方案相比，OS 获益仍然缺失。需要等待正在进行的/精心设计的 3 期 RCT 结果以及关于现有药物在转移性激素敏感性前列腺癌基于 ARSI 联合治疗后对 mCRPC 患者结局的序贯影响的真实世界数据，这将改善治疗时代不断加剧的临床决策。
