Evaluation of systemic therapy and surgical consolidation in patients with node positive upper tract urothelial carcinoma.

Abstract

816 Background: The recommended treatment for high-grade upper tract urothelial carcinoma (UTUC) includes radical nephroureterectomy with regional lymph node dissection for clinically organ-confined disease. The timing of peri-operative systemic therapy is multifactorial, with extrapolation of data from muscle-invasive bladder cancer in the neoadjuvant setting, and level 1 data for UTUC in the adjuvant setting. The timing of peri-operative systemic therapy and need for surgical consolidation in the clinically node positive setting is even more unclear. The goal of this study is to compare survival in cN+ patients managed with neoadjuvant, adjuvant, and systemic therapy alone approaches. Methods: Patients with cT0-4 N1-3 M0 UTUC who received chemotherapy with or without nephroureterectomy (NU) between 2018 and 2021 in the National Cancer Database (NCDB) were included. Patients were stratified into three treatment groups: chemotherapy only (CO), neoadjuvant chemotherapy followed by nephroureterectomy (NAC-NU), and nephroureterectomy followed by adjuvant chemotherapy (NU-AC). OS was analyzed using Kaplan-Meier analysis and log rank tests. Cox proportional hazard models were employed to adjust for potential confounders. Results: A total of 1193 patients were included (CO, NAC-NU, and NU-AC treatment groups consisted of 495, 287, and 411 patients, respectively). Patients in the CO group were older (P<0.001), more commonly males (P<0.001) compared with NAC-NU and NU-AC cohorts. There was no significant difference in Charlson comorbidity index between the three groups. The pathologic complete response rate (ypT0N0) in the NAC-NU was 6.5%. Patients managed with NAC-NU exhibited the most favorable OS compared to NU-AC and CO (P<0.0001), with 3-year OS 65.4% (95% CI 58.4%-73.3%), 53.5% (47.9%-59.6%), and 20.8% (15.7%-27.6%) in these groups, respectively. On multivariate analysis controlling for age, sex, and clinical stage using NAC-NU as a referent, NU-AC and CO exhibited inferior OS (HR 1.48, 95% CI 1.06-2.06, P=0.021 and HR 2.92, 2.14-4.00, P<0.001, respectively). Conclusions: The use of neoadjuvant chemotherapy followed by nephroureterectomy provides optimal survival outcomes in patients with cN+ high-grade UTUC. These data suggest that, when feasible, surgical consolidation is an important treatment component in patients with cN+ disease, likely owing to low rates of pathologic complete response. Estimated overall survival at 1- and 3-year endpoints. Treatment Sample Size 1 Year Survival (95% CI) 3 Year Survival (95% CI) Chemo Alone 348 57.6% (52.5% - 63.2%) 20.8% (15.7% - 27.6%) Chemo before Surgery 202 80.8% (75.4% - 86.6%) 65.4% (58.4% - 73.3%) Surgery before Chemo 329 72.8% (68.1% - 77.8%) 53.5% (47.9% - 59.6