SUO 2017: Neoadjuvant Chemotherapy with Dose Dense MVAC, Associated with Higher Down Staging and Pathologic T0 Rates after Radical Cystectomy

Washington, DC ( Neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer is an established therapy supported by Level 1 evidence, and as such has been incorporated into the guidelines for the management of MIBC. However, despite these recommendations, utilization is not universal, even in eligible patients. One contributing factor is the duration of therapy and the morbidity associated with traditional regimens of MVAC and Gemcitabine and cisplatin chemotherapy (Gem/Cis). 

In an effort to address this, the dose-dense MVAC regimen was introduced.1 With shorter duration and relatively well tolerated administration, it may help alleviate some of the concerns of practicing urologic oncologists. 

The authors of this study utilize their institutional data to examine the uptake of dose-dense MVAC (ddMVAC). They looked at 1116 patients treated with radical cystectomy (RC) over a 9 year period. In this cohort, they assessed for down staging to pT0 according to receipt of NAC and across chemotherapy regimens using logistic regression. Survival differences according to down staging were examined using the Kaplan-Meier method. 

Of the entire cohort, 332 (29%) patients received NAC, which is consistent with many large series for utilization rates – not ideal, but consistent. NAC patients were younger, more likely to be insured, less likely to be pure urothelial, and more likely to have cT3/4 disease. 204 patients received Gem/Cis, 32 Gem/Carbo, and 44 ddMVAC, while 52 had an unknown regimen. 

Interestingly, down-staging was seen in 26% of patients never receiving NAC, likely due to TURBT (and 10% pT0 rate). 

In the patients receiving NAC, down-staging (any) and down-staging to pT0 (complete response) were more common with ddMVAC compared to other chemotherapy regimens. Down-staging rates (any) were 52.2%, 41.3%, and 27% for ddMVAC, gemcitabine/cisplatin and gemcitabine/carboplatin, respectively, while pT0 rates (complete response rates) were 40.9%, 20.6% and 9.4% (p <0.001). In unadjusted and adjusted analyses, ddMVAC was associated with a 1.8 to 2.6 fold increased likelihood of pathological T0 stage after cystectomy compared to gemcitabine/cisplatin. Patients who experienced pathologic down staging had improved overall survival (p=<0.001), which has been established in the literature before.

Based on this institutional series, ddMVAC appears to be associated with higher down-staging and CR rates compared to Gem/Cis. 

Limitations / Discussion Points:

1. Gemcitabine/carboplatin is a substandard chemotherapy regimen and did not need to be included. Gem/cisplatin is an appropriate comparison as it is what most institutions utilize.

2. There was no comment on tolerability, side effects / adverse event profile. This would be interesting to acknowledge, as its one of the reasons ddMVAC may be favored over Gem/Cis.

3. A significant limitation is the lack of info on incomplete treatment – how many patients who were referred for NAC did not complete the treatment regimen (either due to adverse events or progression)? And which regimen did this receive?

This group’s work is a small institutional series, and may help build on the bigger picture. However, there is no head-to-head prospective comparison to date to classic Gem/Cis. A trial comparing ddGC to ddMVAC demonstrated no improvement in results, with slightly lower adverse events.


1. Sternberg CN, de Mulder PH, Schornagel JH et al (2001) Randomized phase III trial of high-dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy and recombinant human granulocyte colony-stimulating factor versus classic MVAC in advanced urothelial tract tumors: European Organization for Research and Treatment of Cancer Protocol no. 30924. J Clin Oncol 19(10):2638–2646

2. Efficacy and safety of dose-dense chemotherapy in urothelial carcinoma. Zhu C, Liu J, Zhang J, Li Q, Lian Q, Xu J, Ma X. Oncotarget. 2017 Mar 31;8(41):71117-71127. doi: 10.18632/oncotarget.16759. eCollection 2017 Sep 19.

Presented by: Dominic Tang, MD

Co-Authors: Charles Peyton MD, Juan Chipollini MD, Richard Reich MD, Wade Sexton MD, Michael Poch MD, Philippe Spiess MD, Jingsong Zhang MD and Scott Gilbert MD, Moffitt Cancer Center, Tampa, FL

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, twitter: @tchandra_uromd at the 18th Annual Meeting of the Society of Urologic Oncology, November 20-December 1, 2017 – Washington, DC