Perioperative DD-MVAC as a safe and efficacious treatment for MIBC: Results of a retrospective community center study with clinical correlates of toxicity and response.

Background:  Despite reassuring data showing efficacy of Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin (DD-MVAC), community oncologists traditionally choose Gemcitabine and Cisplatin (GC) for treatment of Muscle-Invasive Bladder Cancer (MIBC). This retrospective study assessed 2-year overall survival (OS) and 2-year progression-free survival (PFS) in patients at our institution with MIBC (Stage T2-T3) treated with peri-operative DD-MVAC (every 14 days for goal of 4 cycles, some received 3 cycles due to toxicity) and radical cystectomy (robotic-assisted (RARC) or open (ORC)). Secondary endpoints included complete pathologic response (CPR).  Methods:  Fifteen patients with MIBC on peri-operative DD-MVAC at our institution were included and an IRB-approved chart-review was performed. The Kaplan-Meier method was used to summarize OS and PFS, which were both measured from the start of treatment. The log rank test was used to compare outcomes between patient groups.  Results:  The mean age was 63.3+/-9.1 years and 80% were male. 21.4% of patients had T2N0, 35.7% had T3N0, and 42.9% had T2/3N+. 4 patients progressed and died during follow up, 1 of who had micro-papillary histology. OS within the 2-year follow-up was 72.7% +/- 13% and 2-year PFS was 61.3% +/- 15% with no associations with stage, lymph nodes, age, gender, or anemia. Of note, patients with chemotherapy-induced mucositis (4 patients, 26.7%) had a significantly higher risk of disease progression (p = 0.048) and a slightly higher risk of death (p = 0.065). Anemia was the only adverse event in > 50% of patients, both drug-related (66.7%) and postoperative (71.4%). Six patients (40.0%) required early cessation of DD-MVAC (3 cycles) due to drug toxicities, which showed no association with OS (p = 0.76) or PFS (p = 0.82). CPR was identified in 5 (33.3%) patients with down-staging in 5 patients (41.7%).  Conclusions:  DD-MVAC is a safe and efficacious treatment for MIBC in the community setting. Mucositis may serve as a clinical prognosticator for disease progression and overall survival.