Introduction

Level I evidence supports the utility of neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer (BCa). Although this evidence is derived primarily from phase III trials that used the combination of methotrexate/vinblastine/doxorubicin/cisplatin (MVAC) or cisplatin/methotrexate/vinblastine (CMV), the alternative and less toxic regimen gemcitabine/cisplatin (GC) is currently used more commonly for NAC. Since dose dense (dd)-MVAC has mostly replaced traditional MVAC, we aimed to compare pathological response and survival rates in patients with locally advanced BCa receiving ddMVAC versus GC. _x000D_

Methods

We retrospectively reviewed records of patients with urothelial cancer who received NAC and underwent cystectomy at 19 contributing institutions from 2000-2013. Patients with cT3-4aN0M0 were selected for this analysis. The rate of pT0N0 and pT≤1N0 was compared between GC and ddMVAC regimens. A Multivariable Cox proportional hazards regression model for overall mortality was generated to evaluate hazard ratios (HRs) for variables of interest (age, LVI, hydronephrosis, type of chemotherapy regimen, surgical margin). _x000D_

Results

Of 1865 patients undergoing NAC and RC during the study period, 319 met our inclusion criteria (table 1). A significantly lower rate of pT0N0 was observed in the GC arm compared to ddMVAC (14.6% vs. 28.0%; p=0.005). The rate of pT≤1N0 was 30.1% for GC compared to 41.0% for ddMVAC (p=0.07). The Kaplan-Meier mean estimate of overall survival for GC and ddMVAC patients was 4.2 and 7.0 years, respectively (p=0.001). In multivariable cox regression analysis, GC patients were at higher risk of death compared to ddMVAC patients (HR 1.9, 95%CI (1.2-3.1); p=0.006). Presence of LVI (HR 2.1, 95%CI (1.2-3.6); p=0.007), hydronephrosis (HR 1.9, 95%CI (1.3-2.9); p=0.002) and positive surgical margin (HR 1.4, 95%CI (1.2-1.7); p<0.001) were also associated with higher risk of death._x000D_

Conclusions

In our retrospective cohort of locally advanced BCa patients, ddMVAC was associated with a higher rate of pathologic down-staging response and improved longer survival when compared to GC. A clinical trial is warranted to validate these hypothesis-generating results superiority of neoadjuvant ddMVAC in patients with locally advanced BCa._x000D_

Funding

None