Diagnostic dilemmas for upper-tract urothelial carcinoma (UTUC)-grade discordance between endoscopic biopsy and final surgical pathology.

Management of upper tract urothelial carcinoma (UTUC) is predicated on risk stratification, which centers around histologic grading of identified tumors. Here, we review a large multi-center experience of patients undergoing radical nephroureterectomy to determine grade concordance between biopsy and final pathology as well as factors associated with under grading.

We conducted a retrospective cohort study of patients who underwent RNU between January 2000 and December 2020 in the UTUC Collaborative Network (UCAN) database. Of 2,276 patients, 1,552 (60.6%) had recorded biopsy and final pathologic data. Multivariate logistic regression was performed using STATA 18.5 to assess predictors for under grading.

Over 90% of the patient cohort were Caucasian and two-third were male. The median age at radical nephroureterectomy was 72 years. Of biopsies performed interpreted as high grade, 988 (96%) remained high grade on final pathology. Of the 522 biopsies that received an initial low-grade assessment, 255 (49%) were reclassified as high grade. Significant predictors for under grading included familial history of Lynch Syndrome or Lynch-associated cancers (OR = 3.22, P = 0.003) and clinical tumor size greater than 2 cm (OR = 1.59, P = 0.031).

Grade mismatch between biopsy and final pathology occurs in approximately 20% of UTUC cases that underwent RNU (Low-grade: 49%, High-grade: 4%). Nearly 50% of low-grade biopsy tumors were upgraded at final nephroureterectomy pathology. Additional investigation integrating adjuvant diagnostic modalities, cytology at time of diagnosis, and enhanced imaging for larger tumors may aid in appropriate risk stratification.

Urologic oncology. 2026 Mar 27 [Epub ahead of print]

Rachel Blansfield, Jay D Raman, Patrick Hensley, Surena F Matin, Garrett Ungerer, Aaron M Potretzke, Vitaly Margulis, Nirmish Singla, Jonathan Coleman, Roger Li, Philippe E Spiess, Roderick Clark

Department of Urology, Penn State Milton S. Hershey Medical Center, Hershey PA., Department of Urology, University of Kentucky College of Medicine, Lexington KY., Department of Urology, The University of Texas MD Anderson Cancer Center, Houston TX., Department of Urology, Mayo Clinic, Rochester MN., Department of Urology, UT Southwestern, Dallas TX., Department of Urology, Johns Hopkins, Baltimore MD., Department of Urology, Memorial Sloan Kettering, New York NY., Department of Urology, Moffitt Cancer Center, Tampa FL., Department of Urology, Penn State Milton S. Hershey Medical Center, Hershey PA. Electronic address: .