A Multi-Institutional Analysis of Outcomes of Patients with Clinically Node Positive Urothelial Bladder Cancer Treated with Induction Chemotherapy and Radical Cystectomy

Purpose Selected patients with bladder cancer with pelvic lymphadenopathy (cN1-3) are treated with induction chemotherapy followed by radical cystectomy. However, the data on clinical outcomes in these patients are limited. In this study we assess pathological and survival outcomes in patients with cN1-3 disease treated with induction chemotherapy and radical cystectomy. Materials and Methods Data were collected on patients from 19 North American and European centers with cT1-4aN1-N3 urothelial carcinoma who received chemotherapy followed by radical cystectomy between 2000 and 2013. The primary end points were pathological complete (pT0N0) and partial (pT1N0 or less) response rates, with overall survival as a secondary end point. Logistic regression and Cox proportional hazard ratios were used for multivariate analysis of factors predicting these outcomes. Results The total of 304 patients had clinical evidence of lymph node involvement (cN1-N3). Methotrexate/vinblastine/doxorubicin/cisplatin was used in 128 (42%), gemcitabine/cisplatin in 132 (43%) and other regimens in 44 (15%) patients. The pN0 rate was 48% (cN1 - 56%, cN2 - 39%, cN3 - 39%, p=0.03). The complete and partial pathological response rates for the entire cohort were 14.5% and 27%, respectively. The estimated median overall survival time for the cohort was 22 months (IQR 8.0, 54). On Cox regression analysis overall survival was associated with pN0, negative surgical margins, removal of 15 or more pelvic nodes and cisplatin therapy. Conclusions Complete pathological nodal response can be achieved in a proportion of patients with cN1-3 disease receiving induction chemotherapy. The best survival outcomes are observed in male patients on cisplatin regimens with subsequent negative radical cystectomy margins and complete nodal response (pN0) with excision of 15 or more pelvic nodes.