A Comparative Study of Gemcitabine-Cisplatin vs. Dose-Dense MVAC (Methotrexate, Vinblastine, Doxorubicin, and Cisplatin) as Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer: A Single-Institution Experience

Background Muscle-invasive bladder cancer (MIBC) involves a high risk of progression and death. Neoadjuvant chemotherapy (NAC), prior to radical cystectomy (RC), has been shown to improve survival. Gemcitabine-cisplatin (GC) has emerged as a preferred NAC regimen based on its favorable toxicity profile, while dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) may yield better pathologic complete response (pCR) rates, as reported in some studies. Purpose The objective of this study is to compare the efficacy and toxicity profiles of GC and ddMVAC as neoadjuvant regimens in patients with MIBC. Methods This was a retrospective study of 120 patients with clinical stage cT≥2-4a, N+M0 MIBC, treated at a single tertiary cancer center from January 2023 to December 2024. GC was administered to 63 patients, and ddMVAC to 57 patients. Outcomes included pCR, pathologic downstaging, disease-free survival (DFS), overall survival (OS), and toxicity. Results The pCR rate was higher for ddMVAC (22/57 patients, 38.59%) than for GC (14/63 patients, 22.22%) (p = 0.04). Patients with downstaging (≤pT1N0) were more frequent in the ddMVAC group (34/57 patients, 59.64%) compared to the GC group (28/63 patients, 44.44%). The median OS was longer for the ddMVAC group (41.6 months; 95% CI: 35.2-48.9) compared to the GC group (36.8 months; 95% CI: 30.5-42.1) (p = 0.12; HR: 0.82; 95% CI: 0.63-1.06). The incidence of grade ≥3 toxicity was higher for ddMVAC, with 20/57 patients (35%) vs. 10/63 patients (15.87%) for GC. Febrile neutropenia occurred in 8/57 patients (14%) in the ddMVAC group, compared to 3/63 patients (4.76%) in the GC group. Conclusion ddMVAC exhibited higher pCR and downstaging rates than GC, with a tolerable - though higher - rate of toxicity. Both regimens are acceptable options for NAC in MIBC, with treatment choice dependent on each patient's fitness and preferences.