根治性局部治疗后生化复发的挽救治疗：系统评价、Meta分析及网络Meta分析
Salvage therapies for biochemical recurrence after definitive local treatment: a systematic review, meta-analysis, and network meta-analysis
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发表日期:2024 Sep 13
作者:
Akihiro Matsukawa, Takafumi Yanagisawa, Tamas Fazekas, Marcin Miszczyk, Ichiro Tsuboi, Mehdi Kardoust Parizi, Ekaterina Laukhtina, Jakob Klemm, Stefano Mancon, Keiichiro Mori, Shoji Kimura, Jun Miki, Juan Gomez Rivas, Timo F W Soeterik, Thomas Zilli, Derya Tilki, Steven Joniau, Takahiro Kimura, Shahrokh F Shariat, Pawel Rajwa
DOI:
10.1038/s41391-024-00890-4
摘要
在前列腺癌（PCa）局部治疗后，生化复发（BCR）管理的最新进展，包括雄激素受体信号抑制剂（ARSIs）的应用，已拓宽治疗选择范围。我们旨在比较在具有治愈意图的临床非转移性PCa患者中，经过根治性局部治疗后出现BCR的患者的挽救治疗。在2023年10月，我们检索了PubMed、Scopus和Web of Science数据库，以识别关于Radical Prostatectomy（RP）或放疗（RT）后BCR患者挽救治疗疗效的随机对照试验（RCT）和前瞻性研究。主要终点为无转移生存期（MFS），次要终点包括无进展生存期（PFS）和总生存期（OS）。我们纳入了19项研究（n=9117）；其中6项试验分析RP后RT策略，10项分析RP±RT或单独RT的激素策略，3项分析其他药物。在成对Meta分析中，联合激素治疗显著改善了MFS（HR：0.69，95% CI：0.57-0.84，p<0.001），相较于单独RT。根据治疗排名分析，在RT基础策略中，择期淋巴结RT和雄激素剥夺治疗（ADT）的联合是最有效的MFS策略。而在激素策略中，恩扎鲁胺+ADT在MFS和OS方面均显示出最大益处。我们的分析显示，Prostate bed RT、择期盆腔照射和ADT的组合是适合RP后BCR患者的首选治疗。在其他患者或RT后复发者，特别是高风险BCR患者，应考虑联合ADT和ARSI治疗。
Abstract
Recent advancements in the management of biochemical recurrence (BCR) following local treatment for prostate cancer (PCa), including the use of androgen receptor signaling inhibitors (ARSIs), have broadened the spectrum of therapeutic options. We aimed to compare salvage therapies in patients with BCR after definitive local treatment for clinically non-metastatic PCa with curative intent.In October 2023, we queried PubMed, Scopus, and Web of Science databases to identify randomized controlled trials (RCTs) and prospective studies reporting data on the efficacy of salvage therapies in PCa patients with BCR after radical prostatectomy (RP) or radiation therapy (RT). The primary endpoint was metastatic-free survival (MFS), and secondary endpoints included progression-free survival (PFS) and overall survival (OS).We included 19 studies (n = 9117); six trials analyzed RT-based strategies following RP, ten trials analyzed hormone-based strategies following RP ± RT or RT alone, and three trials analyzed other agents. In a pairwise meta-analysis, adding hormone therapy to salvage RT significantly improved MFS (HR: 0.69, 95% CI: 0.57-0.84, p < 0.001) compared to RT alone. Based on treatment ranking analysis, among RT-based strategies, the addition of elective nodal RT and androgen deprivation therapy (ADT) was found to be the most effective in terms of MFS. On the other hand, among hormone-based strategies, enzalutamide + ADT showed the greatest benefit for both MFS and OS.The combination of prostate bed RT, elective pelvic irradiation, and ADT is the preferred treatment for eligible patients with post-RP BCR based on our analysis. In remaining patients, or in case of post-RT recurrence, especially for those with high-risk BCR, the combination of ADT and ARSI should be considered.