The dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) is now recognized as a standard neoadjuvant chemotherapy (NAC) regimen for muscle-invasive bladder cancer (MIBC) and considered superior to gemcitabine-based regimens in the world. However, gemcitabine-based regimens remain primarily used as NAC for MIBC in Japan, with few institutions using dd-MVAC. Reported here is a retrospective evaluation of MIBC patients who underwent RC with NAC-dd-MVAC therapy at our hospital to determine efficacy and safety.

Data for MIBC patients who received NAC-dd-MVAC followed by a radical cystectomy from June 2019 to May 2023 performed at our hospital were analyzed. For comparisons, data for MIBC patients who received NAC gemcitabine and cisplatin (GC) or gemcitabine and carboplatin (GCarbo) therapy between January 2010 and March 2019 were also obtained. Rates of ypT1N0 or less, progression-free survival (PFS), overall survival (OS), and NAC adverse effects were compared between the GC/GCarbo and dd-MVAC regimens.

Results for 32 patients who received dd-MVAC and 30 who received GC/GCarbo NAC therapy were analyzed. ypT1N0 or less was noted in 40.7% of the dd-MVAC and 40.0% of the GC/GCarbo groups, while ypT0N0 rates were 25% and 10%, respectively, with no statistical differences noted. However, Kaplan-Meier analysis of the total cohort demonstrated that dd-MVAC was associated with significantly better PFS and OS rates than GG/GCarbo (hazard ratios: 0.33, p=0.0237, and 0.23, p=0.0127, respectively). Propensity-matched models also showed similar results for both PFS and OS (Figure). Adverse effects (AEs) of dd-MVAC were acceptable and the incidence of hematologic toxicity was lower as compared with GC/GCarbo therapy.

The present study is the first to show efficacy and safety of NAC-dd-MVAC for MIBC patients treated in Japan. Notably, dd-MVAC in an NAC setting led to prolonged PFS and OS in patients with MIBC, while AE incidence was reduced as compared to those who received a conventional gemcitabine-based regimen. Future prospective multicenter studies with larger numbers of MIBC patients treated at Japanese institutions will be necessary to confirm the present results.