ddMVAC versus gemcitabine-cisplatin as neoadjuvant treatment for muscle-invasive urothelial bladder cancer: a...

Cisplatin-based neoadjuvant chemotherapy (NACT) followed by radical cystectomy (RC) is the standard treatment for eligible patients with muscle-invasive bladder cancer (MIBC). However, the comparative effectiveness of gemcitabine/cisplatin (GC) and dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) in routine practice remains insufficiently defined, particularly in broader real-world populations that include patients with regional lymph node involvement. We conducted a multicenter retrospective real-world study of 232 patients with non-metastatic urothelial MIBC treated with cisplatin-based NACT at seven Polish reference cancer centers between 2016 and 2024. One hundred patients received ddMVAC and 132 received GC. We compared pathological response, treatment toxicity, event-free survival (EFS), and overall survival (OS). EFS was defined as the time from NACT initiation to progression during neoadjuvant treatment, failure to undergo RC due to progression or treatment-related deterioration, recurrence after RC, or death from any cause. Univariable and multivariable Cox regression analyses were performed. Cumulative cisplatin dose was assessed using a cutoff of 280 mg/m². Baseline characteristics were generally comparable, although patients treated with ddMVAC had better ECOG performance status. Median treatment duration was shorter with ddMVAC than with GC (6.3 vs. 9 weeks; p < 0.001), while cumulative cisplatin dose was higher (280 vs. 210 mg/m²; p = 0.002). Pathological complete response (pCR) was achieved more frequently with ddMVAC than with GC (39.8% vs. 13.6%; p < 0.001). Median OS was longer in the ddMVAC group (39 vs. 27 months; p = 0.0203), and median EFS was also superior (not reached vs. 20.1 months; p = 0.001). In multivariable analysis, pCR remained independently associated with both OS and EFS, while R0 resection remained independently associated with EFS. Hematologic toxicity and treatment discontinuation due to toxicity were more frequent with GC. In this real-world cohort, ddMVAC was associated with a markedly higher pCR rate than GC. pCR was the strongest independent factor associated with favorable long-term outcomes, while R0 resection was independently associated with improved EFS. These findings support treatment strategies aimed at maximizing pathological response and ensuring timely radical surgery.