Nephroureterectomy for upper tract urothelial carcinoma recurrence in bladder cancer patients treated with radical cystectomy: a multicentric propensity score matched analysis on predictors, practice patterns and survival outcomes

Aim: (I) To determine clinicopathological determinants of metachronous Upper Tract Urothelial Carcinoma (UTUC) requiring Radical Nephroureterectomy (RNU) after Radical Cystectomy (RC). (II) To evaluate long-term survival of patients who underwent RC + RNU compared with matched RC only controls. Methods: Patients undergoing RNU for metachronous UTUC were extracted from a multi-institutional RC database. A 1:2 Propensity Score Match (PSM) was performed based on age, gender, BMI, CCI, Smoking Status, and cT stage between RC only and RC + RNU patients. Simon-Makuch plots, landmark analyses and Multivariable Cox regressions were adopted to compare survival outcomes. Results: Of 1804 RC patients, 85 (4.7%) underwent subsequent RNU. At multivariate regression, younger age, smoking history, BCG exposure, NMIBC, CIS and positive ureteric margins were identified as positive predictors of upper tract recurrence. After PSM, 81 RC + RNU patients were matched to 157 RC only controls. Median time from RC to RNU was 29 (18–47) months, with the majority of UTUC diagnosed at a muscle-invasive stage (70.9%). Simon-Makuch curves demonstrated worse Cancer Specific Survival (CSS) of the RC + RNU cohort (HR: 6.41, 95% CI 3.16–13.04). At landmark analyses, RNU was consistently associated with an increased mortality risk from the 24th month onward. Multivariable Cox regression identified RNU and pN + as the only significant predictors of worse CSS (respectively, HR: 6.55, 95% CI 2.93–14.64 and HR: 8.45, 95% CI 3.24–21.99). Conclusions: The worse survival outcomes and high rates of locally advanced disease found at RNU underscore the need for standardized, risk-stratified, long-term follow-up of the remnant urinary tract following RC.