Abstract
OBJECTIVE: To determine the risk and timing of metachronous upper tract urothelial carcinoma (UTUC) after non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: In this multi-institutional retrospective cohort study involving academic and community hospitals, clinicopathological data were collected from patients with NMIBC treated between 2005 and 2022. Patients with prior or synchronous UTUC at NMIBC diagnosis were excluded. The primary outcome was time to metachronous UTUC, confirmed on pathology or upper tract imaging. Secondary objectives included determining the cumulative incidence of UTUC stratified by the European Association of Urology risk groups and UTUC risk factors identified using Fine and Gray regression, with all-cause mortality as a competing risk. RESULTS: Among 3003 patients, 1158 (39%) were low-risk, 650 (22%) intermediate-risk, 944 (31%) high-risk, and 251 (8%) very high-risk. During a median (interquartile range) follow-up of 4.9 (2.7-8.4) years, 104 patients developed UTUC. On multivariable analysis, multiple tumours were an independent predictor of UTUC (subdistribution hazard ratio 1.86, 95% confidence interval 1.24-2.80; P = 0.003). The 10-year cumulative incidence was 2.2% for low-risk, 4.4% for intermediate-risk, and 6.3% for high- and very high-risk patients. Routine imaging detected UTUC in 40% of low-risk, 58% of intermediate-risk, and 53% of high- and very high-risk patients. High-grade UTUC was found in 36% of low-risk, 63% of intermediate-risk, and 64% of high- and very high-risk patients. The majority of UTUC cases (77%) occurred within 5 years of NMIBC. CONCLUSIONS: The contemporary risk of metachronous UTUC may be lower than historical data. Our findings demonstrate that UTUC incidence is low in patients with low- and intermediate-risk NMIBC and increases in the high- and very high-risk groups. These results support current guideline recommendations to omit routine upper tract imaging in low-risk NMIBC and question its utility in intermediate-risk disease. In high-risk patients, routine imaging remains warranted, although the optimal frequency and duration are yet to be determined.