Effectiveness of Preoperative Chemotherapy and Radical Cystectomy in Clinically Node- Positive and Node-negative Bladder Cancer Patients

Purpose: While preoperative chemotherapy combined with radical cystectomy (RC) is the standard treatment for clinically node-negative (cN0) bladder cancer (BC), the optimal approach for clinically node-positive (cN+) BC remains unclear. We assessed whether combination treatment improves survival in cN+ patients and whether nodal response on imaging predicts survival outcomes. Materials and Methods: We retrospectively analyzed all T2-4N0M0 and T1-4N+M0 patients who received preoperative chemotherapy and RC at our institution between 1999 and 2019. Survival and pathological outcomes were compared between cN0 and cN+ patients. The hazard ratios (HRs) for recurrence-free survival (RFS) and cancer-specific survival (CSS) were compared to published HRs for cN+ patients treated with RC alone, adjusted to reflect clinical rather than pathological node status. We further stratified cN+ patients based on nodal response on imaging and analyzed its prognostic significance. Results: Among 142 patients (73 cN0, 69 cN+), 5-year RFS was 68% in both groups, while 5-year CSS was 80% in cN0 and 70% in cN+ patients. The HR for RFS in cN+ patients was 1.10 (95% Confidence interval [CI]: 0.67-1.80), significantly lower than the adjusted RC-only HR (2.19). The HR for CSS was 1.64 (95% CI: 0.92-2.92), not significantly lower than the adjusted RC-only HR (2.39). Among 72 cN+ patients assessed for nodal response, significant differences were observed in RFS and CSS ( p <0.001 for both). Pathological response was also superior in clinical responders, with significant differences in downstaging ( p =0.03) and mean lymph node density ( p =0.043). Conclusion: Preoperative chemotherapy reduces the RFS difference between cN+ and cN0 BC patients, suggesting a survival benefit for cN+ patients. Additionally, nodal response on imaging is a strong predictor of survival.