Neoadjuvant dose dense MVAC versus GC in patients with cT3-4aN0M0 bladder cancer treated with radical cystectomy

Level I evidence supports the utility of neoadjuvant cisplatin-based chemotherapy (NAC) for muscle invasive bladder cancer (BCa). Since dose dense (ddMVAC) has mostly replaced traditional MVAC, we aimed to compare pathological response and survival rates in patients with locally advanced BCa receiving NAC with ddMVAC versus GC.

We retrospectively reviewed records of patients with urothelial cancer who received NAC and underwent cystectomy at 20 contributing institutions from 2000-2015. Patients with cT3-4aN0M0 were selected for this analysis. The rates of ypT0N0 and ≤ ypT1N0 were compared between GC and ddMVAC regimens. Two multivariable Cox proportional hazards regression models for overall mortality were generated using preoperative and postoperative data.

Of patients undergoing NAC and RC during the study period, 319 met our inclusion criteria. A significantly lower rate of ypT0N0 was observed in the GC arm compared to ddMVAC (14.6% vs. 28.0%; p=0.005). The rate of ≤ ypT1N0 was 30.1% for GC compared to 41.0% for ddMVAC (p=0.07). The Kaplan-Meier mean estimates of overall survival for GC and ddMVAC patients were 4.2 and 7.0 years, respectively (p=0.001). In multivariable cox regression analysis based on preoperative data, GC patients were at higher risk of death compared to ddMVAC patients [HR 2.07 (95% CI 1.25-3.42; p=0.003)]. Presence of LVI [HR 1.97 (95% CI 1.15-3.36; p=0.01)] and hydronephrosis [HR 2.18 [95% CI 1.43-3.30; p<0.001)] were also associated with higher risk of death.

In our retrospective cohort of locally advanced BCa patients, ddMVAC was associated with a higher rate of complete pathologic response and improved survival when compared to GC. A clinical trial is warranted to validate these hypothesis-generating results testing the superiority of neoadjuvant ddMVAC in patients with locally advanced BCa.

The Journal of urology. 2018 Jan 09 [Epub ahead of print]

Homayoun Zargar, Jay B Shah, Bas W van Rhijn, Siamak Daneshmand, Trinity J Bivalacqua, Philippe E Spiess, Peter C Black, Wassim Kassouf

Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada., Department of Urology, MD Anderson Cancer Center, Houston, TX, USA., Department of Urology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands., USC/Norris Comprehensive Cancer Center, Institute of Urology, University of Southern California, CA, USA., Department of Urology, The James Buchanan Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, MD, USA., Department of Genitourinary Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa FL, USA., Department of Surgery (Division of Urology), McGill University Health Center, Montreal, Canada. Electronic address: .