Survival outcomes in patients with muscle-invasive bladder cancer receiving neoadjuvant chemotherapy stratified by number of cycles.
Authors: Chakraborty Anumita , Hasler Jill S , Handorf Elizabeth A. , Anari Fern , Ghatalia Pooja , Miron Benjamin , Plimack Elizabeth R. , Geynisman Daniel M. , Zibelman Matthew R. 
Published: June 2023

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Background: Neoadjuvant cisplatin-based chemotherapy (NAC) prior to radical cystectomy is the standard of care for patients with muscle invasive bladder cancer (MIBC). Three or more cycles of NAC are commonly administered based on outcomes in prior prospective trials, however many patients are intolerant of 3 cycles of NAC due to toxicity. The prognosis of patients receiving fewer than 3 cycles of NAC has yet to be elucidated. Methods: This is a retrospective single-center study to quantify pathologic response, recurrence-free survival (RFS), and overall survival (OS) from time of first NAC in patients treated with < 3 cycles of NAC compared to patients treated with ≥3 cycles of NAC. Inclusion criteria include: diagnosis of MIBC between 2004-2017, ≥5 years of follow up, deceased or had recurrence prior to 5 years follow up but with adequate follow-up data. Patients were excluded from the study if they were found to have metastatic disease prior to initiation of NAC, lost to follow up prior to 5 years with no evidence of recurrence or death, or had progression of disease during NAC. The primary objective of this study was to determine RFS and OS in patients stratified by cycles of NAC. Patient characteristics were compared using chi-square tests, Fisher’s exact tests, and Wilcoxon rank sum tests. Kaplan Meier curves and log-rank tests were used to compare RFS between subgroups, and Cox proportional hazards models were used to compare RFS adjusting for ECOG performance status, baseline GFR, stage, type of NAC regimen, and patient age at first dose of NAC. 5-year OS was calculated as a percentage of patients surviving at 5 years. Results: A total sample of 195 patients were treated with NAC for MIBC, of which 30 (15.3%) patients received < 3 cycles and 165 (84.6%) patients received ≥3 cycles of NAC. 53 patients received gemcitabine and cisplatin (GC) and 142 patients received methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC). Complete pathologic response (ypT0N0) was observed in 7.4% of patients receiving < 3 cycles and in 26.8% of patient receiving ≥3 cycles of NAC (p = 0.024). Significant pathologic response ( < ypT2) was obtained in 22.2% of patients receiving < 3 cycles of NAC and in 41.8% of patients receiving ≥3 cycles (p > 0.05). Median RFS in patients with < 3 cycles of NAC was 8.8 months (95% CI 6.51, 13.4) and 54.5 months with ≥3 cycles of NAC (95% CI 29.8, 111.9). Based on a log-rank test there is a statistically significant difference in unadjusted RFS between the two groups (p < 0.001). The 5-year OS in patients receiving < 3 cycles of NAC was 13.3%, and the 5-year OS in those receiving ≥3 cycles was 53.3%. Conclusions: Early cessation of chemotherapy due to intolerance had significant implications on pathologic response, RFS and OS. Clinicians should prioritize administering at least 3 cycles of cisplatin-based chemotherapy when feasible to optimize outcomes.