Neoadjuvant Chemotherapy with Accelerated Methotrexate, Vinblastine, Doxorubicin, and Cisplatin in Patients with Muscle-invasive Bladder Cancer: A Retrospective Age-stratified Analysis on Safety and Efficacy

Background: The standard of care (SOC) for muscle-invasive bladder cancer (MIBC) includes cisplatin-based combination chemotherapy in the neoadjuvant setting followed by radical cystectomy. Older patients often do not receive SOC due to perceived toxicity concerns despite guideline-directed recommendations.Objective: To characterize the safety and efficacy of neoadjuvant accelerated methotrex-ate, vinblastine, adriamycin, and cisplatin (aMVAC) in MIBC patients as a function of age.Design,setting, and participants: A retrospective analysis was conducted in 186 MIBC patients treated at Fox Chase Cancer Center between January 1, 2002 and December 31, 2018. Adults with histologically proven muscle-invasive urothelial cancer were eli-gible. The exclusion criteria included nonurothelial histology, lack of muscularis propria invasion, and primary upper tract or metastatic disease.Intervention: Neoadjuvant chemotherapy with aMVAC.Outcome measurements and statistical analysis: Patients were stratified by age (<65, 65-74, and >75 yr old). Renal function was assessed at baseline and at time points after treatment. Clinicopathologic variables were compared between age groups to determine efficacy.Results and limitations: There were no statistically significant differences in dose reduc-tions, treatment interruptions, time to surgery, or adverse events when patients were stratified by age in univariate and multivariate analyses. Full safety data were not avail-able due to the retrospective nature of the study. Baseline renal function was signifi-cantly worse among older patients, and the percent decline in creatinine clearance was greater with older age. We found comparable efficacy of aMVAC regardless of age. Conclusions: Accelerated MVAC was safe and demonstrated efficacy in MIBC irrespective of age in this single-center, retrospective study. Careful selection based on clinical variables, and not age, should identify patients able to receive neoadjuvant chemotherapy.