最近，强化治疗的研究势头强劲，三种新的治疗组合被批准用于治疗转移性去势抵抗性前列腺癌（mCRPC）。本系统评价总结了有关 mCRPC 强化策略的当前和新出现的证据，并为理想的治疗测序提供了指导。本次评价遵循系统评价和荟萃分析方案的首选报告项目 (PRISMA-P) 指南。截至 2024 年 5 月 15 日，全面检索了 PubMed、EMBASE、Web of Science、Cochrane Library、ClinicalTrials.gov 和主要国际协会的在线会议记录，查找与 mCRPC 治疗强化和测序相关的术语。总共有 28 项临床试验和 24 项正在进行的临床试验本次综述纳入了强化治疗的研究。根据雄激素受体通路抑制剂 (ARPIs) 联合或不联合多西紫杉醇治疗早期疾病状态，概述了已批准的 mCRPC 治疗的最佳测序算法。在第一线中，聚（ADP-核糖）聚合酶抑制剂 ARPI 组合可改善放射学无进展生存期 (rPFS)，特别是对于那些具有 BRCA1/2 改变的患者。 ipatasertib 阿比特龙的 AKT 抑制剂组合可延长 PTEN 缺失或 PIK3CA/AKT1/PTEN 改变患者的 rPFS。对于存在两种或多种恩杂鲁胺早期进展危险因素的患者，放射性核素 177-Lu-PSMA-617 恩杂鲁胺可延长无进展生存期。讨论了正在进行的 mCRPC 强化方法的研究，以及可用的和潜在的预测和预后生物标志物。单药和强化方法的最近批准和正在进行的研究将不断改变 mCRPC 的治疗格局。应用公认的基因组、分子和临床预测和预后指标来改进患者分析是优化现有疗法的顺序使用的基础。版权所有 © 2024 欧洲泌尿外科协会。由 Elsevier B.V. 出版。保留所有权利。

Recently, research on treatment intensification has gathered momentum, and three novel therapy combinations were approved for metastatic castration-resistant prostate cancer (mCRPC). This systematic review summarizes the current and emerging evidence around intensified strategies for mCRPC and provides guidance for an ideal therapeutic sequencing.Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) guidelines were followed to perform this review. PubMed, EMBASE, Web of Science, Cochrane Library, ClinicalTrials.gov, and major international societies' online proceedings were searched comprehensively until May 15, 2024, for terms related to treatment intensification and sequencing for mCRPC.Overall, 28 clinical trials and 24 ongoing studies of intensification treatments were included in this review. Algorithms of optimal sequencing of approved treatments for mCRPC were outlined according to the use of androgen receptor pathway inhibitors (ARPIs) with or without docetaxel for earlier disease states. In first line, poly(ADP-ribose) polymerase inhibitor + ARPI combinations improve radiographical progression-free survival (rPFS), particularly for those with BRCA1/2 alterations. The AKT inhibitor combination of ipatasertib + abiraterone extends rPFS in those with PTEN loss or PIK3CA/AKT1/PTEN alterations. In those with two or more risk factors for early progression on enzalutamide, radionuclide 177-Lu-PSMA-617 + enzalutamide prolongs progression-free survival. Ongoing research of intensified approaches for mCRPC, and available and potential predictive and prognostic biomarkers are discussed.Recent approvals and ongoing investigations of single agents and intensification approaches will keep transforming the mCRPC treatment landscape. Improvement of patient profiling applying recognized genomic, molecular, and clinical predictive and prognostic indicators is fundamental to optimize sequential use of available therapies.Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.