Comparing Preoperative Chemotherapy Regimens in Patients with Muscle-Invasive Bladder Cancer - Expert Commentary

Neoadjuvant cisplatin-based chemotherapy in patients with muscle-invasive bladder cancer (MIBC) before radical cystectomy improves overall survival. Commonly used neoadjuvant chemotherapy regimens include the combination of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) or a combination of gemcitabine and cisplatin (GC).

The results of a recent randomized phase III  trial comparing response rates and toxicities between the dd-MVAC and GC regimens was published by Pfister et al. in European Urology. The study randomized 500 patients to either 6 cycles of dd-MVAC every 2 weeks or 4 cycles of GC every 3 weeks. Patients with primary bladder tumor histologically confirmed as urothelial carcinoma with no metastasis or lymph node involvement were eligible for the trial. 58% and 66% of patients completed treatment with dd-MVAC and GC, respectively.

In the dd-MVAC arm, 129 (52%) developed hematological toxicities, and asthenia was observed in 35 (14%) patients. In patients receiving the GC regimen, 134 (55%) patients developed hematological toxicities, while 10 (4.1%) reported asthenia. In addition, gastrointestinal disorders and severe anemia were observed more frequently in the dd-MVAC arm than in the GC arm.  Complete pathological responses (ypT0pN0) were similar in the dd-MVAC and GC arm (42% vs. 36, p=0.02). On the other hand, pathological downstaging (ypT1N0 or less) was higher in the dd-MVAC than GC arm (63% vs. 49%, p = 0.007).

As expected, fewer patients were able to complete 6 cycles of dd-MVAC compared to 4 cycles of GC. Therefore, adoption of a 6 cycle dd-MVAC regimen in the neoadjuvant setting is likely to be challenging. In addition, whether the higher local control rates observed in the trial on the dd-MVAC arm translate into better overall survival outcomes remains to be seen.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York


  1. Pfister C, Gravis G, Fléchon A, Soulié M, Guy L, Laguerre B, et al. Randomized Phase III Trial of Dose-dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin, or Gemcitabine and Cisplatin as Perioperative Chemotherapy for Patients with Muscle-invasive Bladder Cancer. Analysis of the GETUG/AFU V05 VESPER Trial Seconda. Eur Urol. 2021 Feb;79(2):214–21.

Read the Abstract
email news signup