Yanagisawa Takafumi, Matsukawa Akihiro, Teoh Jeremy Yuen-Chun, Mori Keiichiro, Kawada Tatsushi, Katayama Satoshi, Rajwa Paweł, Quhal Fahad, Pradere Benjamin, Moschini Marco, Shariat Shahrokh F, Miki Jun, Kimura Takahiro
Department of Urology, The Jikei University School of Medicine, Tokyo, Japan.
Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Bladder Cancer. 2025 Apr 25;11(2):23523735251335122. doi: 10.1177/23523735251335122. eCollection 2025 Apr-Jun.
Several phase III randomized controlled trials (RCTs) have shown the importance of perioperative systemic therapy, especially for the efficacy of immune checkpoint inhibitors (ICIs) in both neoadjuvant and adjuvant settings for muscle-invasive bladder cancer (MIBC).
To synthesize the growing evidence on the efficacy and safety of systemic therapies for MIBC utilizing the data from RCTs.
Three databases and ClinicalTrials.gov were searched in October 2024 for eligible RCTs evaluating oncologic outcomes in MIBC patients treated with systemic therapy. We evaluated pathological complete response (pCR), disease-free survival (DFS), progression-free survival (PFS), event-free survival (EFS), overall survival (OS), and adverse events (AEs).
Thirty-three RCTs (including 14 ongoing trials) were included in this systematic review. Neoadjuvant chemotherapy improved OS compared to radical cystectomy alone. Particularly, the VESPER trial demonstrated that dd-MVAC provided oncological benefits over GC alone in terms of pCR rates, OS (HR: 0.71), and PFS (HR: 0.70). Recently, the NIAGARA trial showed that perioperative durvalumab plus GC outperformed GC alone in terms of pCR rates, OS (HR: 0.75), and EFS (HR: 0.68). Despite the lack of data on overall AE rates in the VESPER trial, differential safety profiles in hematologic toxicity were reported between dd-MVAC and durvalumab plus GC regimens. In the adjuvant setting, no study provided the OS benefit from adjuvant chemotherapy. However, only adjuvant nivolumab had significant DFS and OS benefits compared to placebo.
Neoadjuvant chemotherapy remains the current standard of care for MIBC. Durvalumab shed light on the promising impact of ICIs added to neoadjuvant chemotherapy. Nivolumab is the only ICI recommended as adjuvant therapy in patients who harbored adverse pathologic outcomes. Ongoing trials will provide further information on the impact of combination therapy, including chemotherapy, ICIs, and enfortumab vedotin, in both neoadjuvant and adjuvant settings.
多项III期随机对照试验（RCT）已表明围手术期全身治疗的重要性，尤其是免疫检查点抑制剂（ICI）在肌肉浸润性膀胱癌（MIBC）新辅助和辅助治疗中的疗效。
利用RCT数据综合关于MIBC全身治疗疗效和安全性的越来越多的证据。
2024年10月检索了三个数据库和ClinicalTrials.gov，以查找评估接受全身治疗的MIBC患者肿瘤学结局的合格RCT。我们评估了病理完全缓解（pCR）、无病生存期（DFS）、无进展生存期（PFS）、无事件生存期（EFS）、总生存期（OS）和不良事件（AE）。
本系统评价纳入了33项RCT（包括14项正在进行的试验）。与单纯根治性膀胱切除术相比，新辅助化疗改善了总生存期。特别是，VESPER试验表明，在pCR率、总生存期（HR：0.71）和无进展生存期（HR：0.70）方面，剂量密集型甲氨蝶呤、长春花碱、阿霉素和顺铂（dd-MVAC）比单纯吉西他滨联合顺铂（GC）具有肿瘤学益处。最近，NIAGARA试验表明，围手术期度伐利尤单抗联合GC在pCR率、总生存期（HR：0.75）和无事件生存期（HR：0.68）方面优于单纯GC。尽管VESPER试验缺乏总体不良事件发生率的数据，但报告了dd-MVAC与度伐利尤单抗联合GC方案在血液学毒性方面的不同安全性特征。在辅助治疗中，没有研究表明辅助化疗能带来总生存期益处。然而，与安慰剂相比，只有辅助纳武利尤单抗具有显著的无病生存期和总生存期益处。
新辅助化疗仍然是MIBC当前的标准治疗方法。度伐利尤单抗揭示了ICI添加到新辅助化疗中的有前景的影响。纳武利尤单抗是唯一被推荐用于有不良病理结局患者的辅助治疗的ICI。正在进行的试验将提供关于联合治疗（包括化疗、ICI和恩扎妥昔单抗）在新辅助和辅助治疗中的影响的更多信息。
