Indirect Comparison of Neoadjuvant Treatment Strategies for Muscle-Invasive Bladder Cancer: ddMVAC and Perioperative Durvalumab-Gemcitabine-Cisplatin Versus Gemcitabine-Cisplatin: A Systematic Review and Network Meta-Analysis of Randomised Controlled Trials
A partir d'une revue systématique de la littérature publiée jusqu'en mars 2025 (3 essais randomisés), cette méta-analyse évalue l'efficacité, du point de vue du taux de réponse pathologique complète, de la survie sans progression et de la survie globale, et la toxicité de plusieurs stratégies périopératoires (chimiothérapies ou chimio-immunothérapies) pour traiter des patients atteints d'un cancer de la vessie sans envahissement musculaire traité par cystectomie radicale
For cisplatin-eligible patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC), neoadjuvant cisplatin-based chemotherapy (NAC) is standard of care. More intensive regimens such as dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (ddMVAC) and chemoimmunotherapy with durvalumab plus gemcitabine-cisplatin (D-GC) have shown superior outcomes. This network meta-analysis (NMA) compares the efficacy of ddMVAC, D-GC and GC and explores the efficacy thresholds for emerging therapy options, such as enfortumab vedotin plus pembrolizumab (EV-P), to surpass current standards. Following PROSPERO registration (CRD420251077606), systematic searches of PubMed, CENTRAL and Web of Science were conducted to March 2025. Randomised controlled trials (RCTs) comparing neoadjuvant regimens in cisplatin-eligible MIBC were included. A random-effects NMA was performed. Simulations explored hypothetical hazard ratios (HRs) for EV-P. Three RCTs were included. ddMVAC (HR 0.75, 95% CI 0.58–0.98; p = 0.034) and D-GC (HR 0.75, 95% CI 0.66–0.85; p < 0.001) improved overall survival (OS) versus GC, without differences between ddMVAC and D-GC (HR 0.99, 95% CI 0.75–1.33; p = 0.97). Both regimens improved progression-free survival. D-GC achieved higher pathological complete response (pCR) versus GC (OR 1.57, 95% CI 1.21–2.03; p < 0.001), whereas ddMVAC did not. No significant difference in pCR was found between ddMVAC and D-GC. Simulation-NMA suggested EV-P would need to achieve HR ≤ 0.45 versus GC to outperform ddMVAC and D-GC. Limitations include few trials and indirect comparisons. DdMVAC and D-GC improve survival compared with GC in neoadjuvant MIBC. Alternative therapeutic strategies must demonstrate substantial survival benefits to warrant replacing established neoadjuvant regimens.
International Journal of Cancer , article en libre accès, 2026