High-intensity local treatment of clinical node-positive urothelial carcinoma of the bladder alongside systemic chemotherapy improves overall survival

Purpose: Clinical node-positive urothelial carcinoma of the bladder (cN+UCaB) is a rapidly fatal disease with limited information on comparative-effectiveness of available treatment options. We sought to examine the impact of high-intensity vs. conservative local treatment (LT) regimens in management of these patients alongside systemic chemotherapy. Materials and methods: We identified 3,227 patients within the National Cancer Data Base who underwent multiagent systemic chemotherapy along with either high-intensity or conservative LT for primary cN+UCaB between 2004–2016. Patients who received no LT, TURBT alone, or <50 Gy radiation therapy to the bladder were included in the conservative group, while patients that received radical cystectomy with pelvic lymphadenectomy or ≥50 Gy radiation therapy with TURBT were included in the high-intensity group. Inverse probability of treatment weighting (IPTW) adjusted Kaplan-Meier and Cox regression analyses were used to assess overall survival (OS). Additionally, to assess whether the benefit of high-intensity LT differs by baseline mortality risk, we tested an interaction between 5-year predicted life-expectancy and the LT type. Results: Overall, 784 (24.3%) and 2,443 (75.7%) cN+UCaB patients underwent high-intensity and conservative LT, respectively. IPTW-adjusted Kaplan-Meier analysis demonstrated OS to be significantly higher in the high-intensity group compared to the conservative group: 5-year OS 28.4% vs. 18.3%, respectively (Log-rank P<0.001). IPTW-adjusted multivariable Cox regression analysis confirmed the benefit of high-intensity LT in prolonging OS (HR 0.63, P<0.001). Interaction analysis showed that high-intensity LT approach was associated with longer OS in all patients regardless of their baseline 5-year life-expectancy (P_interaction=0.79). Conclusion: Eligible patients with cN+UCaB should be considered for aggressive local treatment alongside multiagent systemic chemotherapy. Prospective trials are needed to validate these preliminary findings.