Background: Although previous literature shows tumor location as a prognostic factor in upper tract urothelial carcinoma (UTUC), there remains uninvestigated regarding the impact of tumor location on grade concordance and discrepancies between ureteroscopic (URS) biopsy and final radical nephroureterectomy (RNU) pathology. Methods: In this international study, we retrospectively reviewed the records of 1,498 patients with UTUC who underwent diagnostic URS with concomitant biopsy followed by RNU between 2005 and 2020. Tumor location was divided into four sections: the calyceal-pelvic system, proximal ureter, middle ureter, and distal ureter. Patients with multifocal tumors were excluded from the study. We performed multiple comparison tests and logistic regression analyses. Results: Overall, 1,154 patients were included; 54.4% of those with low-grade URS biopsies were upgraded on RNU. In the multiple comparison tests, middle ureter tumors exhibited the highest probability of upgrading, meanwhile pelvicalyceal tumors exhibited the lowest probability of upgrading (73.7% vs 48.5%, p = 0.007). Downgrading was comparable across all tumor locations. On multivariate analyses, middle ureteral location was significantly associated with a low probability of grade concordance (odds ratio [OR] 0.59; 95% confidence interval [CI], 0.35-1.00; p = 0.049) and an increased risk of upgrading (OR 2.80; 95% CI, 1.20-6.52; p = 0.017). The discordance did not vary regardless of caliceal location, including the lower calyx. Conclusions: Middle ureteral tumors diagnosed to be low grade had a high probability to be undergraded. Our data can inform providers and their patients regarding the likelihood of undergrading according to tumor location, facilitating patient counseling and shared decision making regarding the choice of kidney sparing vs RNU.

Cancer Prognostics and Health Outcomes Unit University of Montreal Health Centre Montreal Canada

Department of Urology 2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Urology Cantonal Hospital of Lucerne Lucerne Switzerland

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria

Department of Urology Faculty of Medicine Kindai University Osakasayama Japan

Department of Urology Fundació Puigvert Autonoma University of Barcelona Barcelona Spain

Department of Urology Hospital Pontchaillou CHU Rennes Rennes France

Department of Urology Icahn School of Medicine at Mount Sinai Hospital New York New York USA

Department of Urology Institut Universitaire du Cancer Toulouse France

Department of Urology Mayo Clinic Rochester Minnesota USA

Department of Urology Norris Comprehensive Cancer Center University of Southern California Los Angeles California USA

Department of Urology Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Okayama Japan

Department of Urology St Marianna University School of Medicine Kanagawa Japan

Department of Urology University of Texas Southwestern Medical Center Dallas Texas USA

Department of Urology Uro Oncology Robot Assisted and Reconstructive Surgery University of Cologne Cologne Germany

Department of Urology Weill Cornell Medical College New York New York USA

Division of Urology Penn State Health Milton S Hershey Medical Center Hershey Pennsylvania USA

GRC 5 Predictive Onco Uro AP HP Urology Pitie Salpetriere Hospital Sorbonne University Paris France

Hourani Center for Applied Scientific Research Al Ahliyya Amman University Amman Jordan

Karl Landsteiner Institute of Urology and Andrology Vienna Austria

Unit of Oncologic Minimally Invasive Urology and Andrology Careggi Hospital Department of Clinical and Experimental Medicine University of Florence Firenze Italy

Vattikuti Urology Institute Center for Outcomes Research Analytics and Evaluation Henry Ford Health System Vattikuti Urology Institute Detroit Michigan USA

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