Predictors and Patterns of Nonurothelial Recurrence After Nephroureterectomy for Upper Tract Urothelial Carcinoma (UCAN Collaboration)

After radical nephroureterectomy for upper tract urothelial carcinoma, 25% of patients experience distant metastasis within 5 years. Nonurothelial recurrence is associated with poor prognosis and survival, with ∼80% of patients dying within 2 years. We evaluated predictors, patterns, and timing of recurrences after radical nephroureterectomy, and the association between recurrence location and cancer-specific survival.

Separate competing risk regression models were conducted with each site as the outcome and all other recurrence sites as the competing risk. A Cox proportional hazards model was used to evaluate predictors and the association between cancer-specific survival and recurrence site, adjusting for time from surgery to recurrence. A separate model including multiple sites (yes/no) was used to evaluate the association with cancer-specific survival, also adjusting for recurrence sites.

Two thousand one hundred seventy-seven patients with upper tract urothelial carcinoma underwent radical nephroureterectomy between January 2000 and February 2021 in 7 institutions, with 454 developing nonurothelial recurrence (survivor median follow-up, 34 [IQR 11-70] months). Improved cancer-specific survival rates were seen in lung and lymph node metastasis compared with other sites (HR 0.60, 95% CI 0.37-0.97, P = .038; HR 0.65, 95% CI 0.41-1.02, P = .063, respectively). Recurrence to multiple concurrent nonurothelial sites was associated with worse cancer-specific survival rates (HR 1.68, 95% CI 1.30-2.17, P < .001). Significant recurrence associations included tumor size, high stage/grade, and tumor location. There were no statistically significant survival differences based on timing of recurrence.

Recurrences were common within 2 years. Lung/lymph node recurrences portended the most favorable cancer-specific survival rates. Understanding the timing and location of recurrence can tailor surveillance strategies.