Matsukawa Akihiro, Cormio Angelo, Miszczyk Marcin, Parizi Mehdi Kardoust, Fazekas Tamás, Tsuboi Ichiro, Mancon Stefano, Schulz Robert J, Litterio Giulio, Laukhtina Ekaterina, Rajwa Paweł, Seisen Thomas, Mori Keiichiro, Sanguedolce Francesca, Galosi Andrea Benedetto, Miki Jun, Kimura Takahiro, Shariat Shahrokh F, Yanagisawa Takafumi
Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Jikei University School of Medicine, Tokyo, Japan; Division of Anatomy, Medical University of Vienna, Vienna, Austria.
Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Division of Anatomy, Medical University of Vienna, Vienna, Austria; Department of Urology, Azienda Ospedaliero-Universitaria Ospedali Riuniti Di Ancona, Università Politecnica Delle Marche, Ancona, Italy.
Eur Urol Oncol. 2025 Apr 26. doi: 10.1016/j.euo.2025.02.009.
The availability of immune checkpoint inhibitors (ICIs) has expanded perioperative treatment options for urothelial carcinoma. Our aim was to evaluate the effect of neoadjuvant ICI-based regimens on oncological outcomes for patients with muscle-invasive bladder cancer (MIBC).
We systematically searched MEDLINE, Embase, Web of Science, and ClinicalTrials.gov in September 2024 for studies on neoadjuvant therapies for MIBC. A proportion meta-analysis and network meta-analysis (NMA) using random-effect models were conducted to evaluate pooled pathological complete response (pCR) rates and to compare overall survival (OS) and adverse events. The review is registered on PROSPERO (CRD42024587964).
We included 12 randomized controlled trials (RCTs; 5004 patients) and 35 non-RCTs (2964 patients). ICI-chemotherapy combination therapy was associated with a significantly higher pCR rate versus chemotherapy alone (40.6% vs 17.9%; p < 0.01). In the two phase 3 RCTs included (1556 patients) there was no significant difference in OS between dose-dense methotrexate + vinblastine + Adriamycin + cisplatin (ddMVAC) and durvalumab + gemcitabine + cisplatin (GC; hazard ratio 1.06, 95% confidence interval [CI] 0.72-1.55; p = 0.8). ddMVAC significantly increased the risk of grade ≥3 anemia (risk ratio [RR] 2.81, 95% CI 1.62-4.88) and asthenia (RR 3.46, 95% CI 1.68-7.14) in comparison to GC, while durvalumab + GC did not. Limitations include data heterogeneity across studies and the limited number of studies included in the NMA.
ICI addition to chemotherapy in the neoadjuvant MIBC setting significantly increased pCR rates in comparison to chemotherapy alone. However, there was no difference in OS between durvalumab + GC and ddMVAC. Further studies are needed to clarify the OS benefit of ICI-based combination therapy in comparison to the current standard chemotherapy regimen.
免疫检查点抑制剂（ICI）的出现扩展了尿路上皮癌围手术期的治疗选择。我们的目的是评估基于新辅助ICI方案对肌层浸润性膀胱癌（MIBC）患者肿瘤学结局的影响。
我们于2024年9月系统检索了MEDLINE、Embase、科学网和ClinicalTrials.gov，以查找关于MIBC新辅助治疗的研究。采用随机效应模型进行比例荟萃分析和网络荟萃分析（NMA），以评估汇总的病理完全缓解（pCR）率，并比较总生存期（OS）和不良事件。该综述已在PROSPERO（CRD42024587964）上注册。
我们纳入了12项随机对照试验（RCT；5004例患者）和35项非RCT（2964例患者）。与单纯化疗相比，ICI-化疗联合治疗的pCR率显著更高（40.6%对17.9%；p<0.01）。在纳入的两项3期RCT（1556例患者）中，剂量密集型甲氨蝶呤+长春碱+阿霉素+顺铂（ddMVAC）与度伐利尤单抗+吉西他滨+顺铂（GC）之间的OS无显著差异（风险比1.06，95%置信区间[CI]0.72-1.55；p=0.8）。与GC相比，ddMVAC显著增加了≥3级贫血（风险比[RR]2.81，95%CI 1.62-4.88）和乏力（RR 3.46，95%CI 1.68-7.14）的风险，而度伐利尤单抗+GC则没有。局限性包括各研究间的数据异质性以及NMA纳入的研究数量有限。
在新辅助MIBC治疗中，与单纯化疗相比，ICI联合化疗显著提高了pCR率。然而，度伐利尤单抗+GC与ddMVAC之间的OS无差异。需要进一步研究以阐明与当前标准化疗方案相比，基于ICI的联合治疗的OS获益情况。
