University of Colorado Cancer Center, Division of Medical Oncology, Department of Medicine, Aurora, CO.
University of Colorado Cancer Center, Population Health Shared Resource, Aurora, CO.
Urology. 2024 Jun;188:118-124. doi: 10.1016/j.urology.2024.04.034. Epub 2024 Apr 28.
To determine whether neoadjuvant gemcitabine and cisplatin (GC) vs dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) before radical cystectomy improves overall survival (OS), progression-free survival (PFS), and pathologic complete response (pCR) for patients with muscle-invasive bladder cancer with secondary analyses of pathological downstaging and toxicity.
This systematic review and meta-analysis identified studies of patients with muscle-invasive bladder cancer treated with neoadjuvant GC compared to ddMVAC from PubMed, Web of Science, and EMBASE. Random-effect models for pooled log-transformed hazard ratios (HR) for OS and PFS and pooled odds ratios for pCR and downstaging were developed using the generic inverse variance method and Mantel-Haenszel method, respectively.
Ten studies were identified (4 OS, 2 PFS, and 6 pCR clinical endpoints). Neoadjuvant ddMVAC improved OS (HR 0.71 [95% confidence intervals 0.56; 0.90]), PFS (HR 0.76 [95% confidence intervals 0.60; 0.97]), and pathological downstaging (odds ratio 1.34 [95% confidence interval 1.01; 1.78]) as compared to GC. There was no significant difference between regimens for pCR rates (odds ratio 1.38 [95% confidence interval 0.90; 2.12]). Treatment toxicity was greater with ddMVAC. Limitations result from differences in number of ddMVAC cycles and patient selection between studies.
Neoadjuvant ddMVAC is associated with improved OS and PFS vs gemcitabine/cisplatin for patients with muscle-invasive bladder cancer before radical cystectomy. Although rates of pathological complete response were not significantly different, pathological downstaging correlated with OS. ddMVAC should be preferred over gemcitabine/cisplatin for patients with muscle-invasive bladder cancer who can tolerate its greater toxicity.
确定根治性膀胱切除术前行新辅助吉西他滨和顺铂（GC）与密集剂量甲氨蝶呤、长春碱、多柔比星和顺铂（ddMVAC）相比，是否能提高肌层浸润性膀胱癌患者的总生存（OS）、无进展生存（PFS）和病理完全缓解（pCR），并进行了病理降期和毒性的辅助分析。
本系统评价和荟萃分析从 PubMed、Web of Science 和 EMBASE 中确定了新辅助 GC 治疗肌层浸润性膀胱癌患者的研究，并与 ddMVAC 进行了比较。采用通用倒数方差法和 Mantel-Haenszel 法，分别建立了 OS 和 PFS 的汇总对数转换风险比（HR）和 pCR 和降期的汇总优势比的随机效应模型。
确定了 10 项研究（4 项 OS，2 项 PFS 和 6 项 pCR 临床终点）。与 GC 相比，新辅助 ddMVAC 可改善 OS（HR 0.71 [95%置信区间 0.56；0.90]）、PFS（HR 0.76 [95%置信区间 0.60；0.97]）和病理降期（优势比 1.34 [95%置信区间 1.01；1.78]）。两种方案的 pCR 率无显著差异（优势比 1.38 [95%置信区间 0.90；2.12]）。ddMVAC 的治疗毒性更大。局限性源于研究之间 ddMVAC 周期数和患者选择的差异。
与吉西他滨/顺铂相比，肌层浸润性膀胱癌患者在根治性膀胱切除术前接受 ddMVAC 治疗，可提高 OS 和 PFS。虽然病理完全缓解率无显著差异，但病理降期与 OS 相关。ddMVAC 应优于吉西他滨/顺铂，用于能够耐受其更大毒性的肌层浸润性膀胱癌患者。
