Comparative analysis of three vs. four cycles of neoadjuvant gemcitabine and cisplatin for muscle invasive bladder cancer

PURPOSEBecause the optimal number of cycles of neoadjuvant gemcitabine and cisplatin chemotherapy (GC) is unclear, we aimed to compare disease response and survival outcomes of patients receiving either 3 or 4 cycles of neoadjuvant GC for muscle-invasive bladder cancer (MIBC). METHODSA total of 166 patients who were treated with neoadjuvant GC and radical cystectomy for clinical stage T2-4N0M0 were identified. Response and effectiveness of different cycle counts were assessed using downstaging (complete pathologic and partial pathologic response), cancer-specific survival (CSS), and overall survival (OS). Response and survival outcomes were examined with adjusted logistic regression and Cox regression models. Statistical significance was defined as P < 0.05. RESULTSOf 166 patients who received neoadjuvant GC, 107 (64.5%) received 3 cycles and 59 (35.5%) received 4 cycles. Age, insurance, comorbidity, tumor histology (pure urothelial carcinoma, urothelial with divergent differentiation, variant histology), and tumor stage were similar between the 2 treatment groups. Rates of complete response or any downstaging were similar between groups (21.5% and 40.2% in the 3-cycle group and 20.3% and 44.1% in the 4-cycle group, respectively). While disease response was similar (OR 1.03, 95% CI 0.43-2.45), both cancer-specific survival (HR 1.69, 95% CI 0.87-3.26) and overall survival (HR:1.88, 95% CI:1.02-3.48) were more favorable among patients managed with 4 cycles of neoadjuvant chemotherapy compared to those who received 3 cycles in adjusted models. CONCLUSIONSOur analysis demonstrated that survival outcomes tended to be better among patients who received 4 cycle of neoadjuvant GC compared to those treated with 3 cycles. Although potential benefits of omission of fourth cycle may include expedited time to surgery, reduced chemotherapy-associated toxicity, and lower treatment costs, continuation of treatment with a fourth cycle of neoadjuvant GC chemotherapy may benefit patients with muscle-invasive bladder cancer and further improve disease outcomes.