Neoadjuvant Dose Dense MVAC versus Gemcitabine and Cisplatin in Patients with cT3-4aN0M0 Bladder Cancer Treated with Radical Cystectomy

Abstract

Purpose: Level I evidence supports the usefulness of neoadjuvant cisplatin based chemotherapy for muscle invasive bladder cancer. Since dose dense MVAC (methotrexate, vinblastine, doxorubicin and cisplatin) has mostly replaced traditional MVAC, we compared pathological response and survival rates in patients with locally advanced bladder cancer who received neoadjuvant chemotherapy with dose dense MVAC vs gemcitabine and cisplatin.

Materials and methods: We retrospectively reviewed the records of patients with urothelial cancer who received neoadjuvant chemotherapy and underwent cystectomy at a total of 20 contributing institutions from 2000 to 2015. Patients with cT3-4aN0M0 disease were selected for this analysis. The rates of ypT0N0 and ypT1N0 or less were compared between the gemcitabine and cisplatin, and dose dense MVAC regimens. Two multivariable Cox proportional hazards regression models of overall mortality were generated using preoperative and postoperative data.

Results: Of the patients who underwent neoadjuvant chemotherapy and radical cystectomy during the study period 319 met our inclusion criteria. A significantly lower rate of ypT0N0 was observed in the gemcitabine and cisplatin arm than in the dose dense MVAC arm (14.6% vs 28.0%, p = 0.005). The rate of ypT1N0 or less was 30.1% for gemcitabine and cisplatin compared to 41.0% for dose dense MVAC (p = 0.07). The mean Kaplan-Meier estimates of overall survival in the gemcitabine and cisplatin, and dose dense MVAC groups were 4.2 and 7.0 years, respectively (p = 0.001). On multivariable cox regression analysis based on preoperative data patients who received gemcitabine and cisplatin were at higher risk for death than patients who received dose dense MVAC (HR 2.07, 95% CI 1.25-3.42, p = 0.003). Lymph node invasion (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.

Conclusions: In our retrospective cohort of patients with locally advanced bladder cancer dose dense MVAC was associated with higher complete pathological response and improved survival rates compared to gemcitabine and cisplatin. A clinical trial is warranted to validate these hypothesis generating results to test the superiority of neoadjuvant dose dense MVAC in patients with locally advanced bladder cancer.

Keywords: M-VAC protocol; cisplatin; gemcitabine; mortality; urinary bladder neoplasms.