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

Purpose: 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.

Materials and Methods: 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.

Results: 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.

Conclusions: 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.
Andrew B Katims,1,2 Amy L Tin,3 Melissa Assel,3 Patrick Hensley,4 Roger Li,5, Vitaly Margulis,6 Surena Matin,7 Maximilian Pallauf,8 Roderick K Clark,9 Jay D Raman,9 Nirmish Singla,8 Philippe E Spiess,5 Jonathan Coleman,1

  1. Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
  2. Department of Urology, New York Medical College, Valhalla, New York.
  3. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
  4. Department of Urology, University of Kentucky College of Medicine, Lexington, Kentucky.
  5. Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, Florida.
  6. Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas.
  7. Department of Urology, University of Texas MD Anderson Cancer Center, Houston, Texas.
  8. Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  9. Department Urology, Penn State Health, Hershey, Pennsylvania.
Source: Katims AB, Tin AL, Assel M, Hensley P, Li R, Margulis V, Matin S, Pallauf M, Clark RK, Raman JD, Singla N, Spiess PE, Coleman J. Predictors and Patterns of Nonurothelial Recurrence After Nephroureterectomy for Upper Tract Urothelial Carcinoma (UCAN Collaboration). J Urol. 2025 Oct;214(4):407-414. doi: 10.1097/JU.0000000000004646. Epub 2025 Jun 17. PMID: 40526449; PMCID: PMC12355653.