Biological and prognostic implications of biopsy upgrading for high-grade upper tract urothelial carcinoma at nephroureterectomy.

Technical limitations of ureteroscopic (URS) biopsy has been considered responsible for substantial upgrading rate in upper tract urothelial carcinoma (UTUC). However, the impact of tumor specific factors for upgrading remain uninvestigated.

Patients who underwent URS biopsy were included between 2005 and 2020 at 13 institutions. We assessed the prognostic impact of upgrading (low-grade on URS biopsy) versus same grade (high-grade on URS biopsy) for high-grade UTUC tumors on radical nephroureterectomy (RNU) specimens.

This study included 371 patients, of whom 112 (30%) and 259 (70%) were biopsy-based low- and high-grade tumors, respectively. Median follow-up was 27.3 months. Patients with high-grade biopsy were more likely to harbor unfavorable pathologic features, such as lymphovascular invasion (p < 0.001) and positive lymph nodes (LNs; p < 0.001). On multivariable analyses adjusting for the established risk factors, high-grade biopsy was significantly associated with worse overall (hazard ratio [HR] 1.74; 95% confidence interval [CI], 1.10-2.75; p = 0.018), cancer-specific (HR 1.94; 95% CI, 1.07-3.52; p = 0.03), and recurrence-free survival (HR 1.80; 95% CI, 1.13-2.87; p = 0.013). In subgroup analyses of patients with pT2-T4 and/or positive LN, its significant association retained. Furthermore, high-grade biopsy in clinically non-muscle invasive disease significantly predicted upstaging to final pathologically advanced disease (≥pT2) compared to low-grade biopsy.

High tumor grade on URS biopsy is associated with features of biologically and clinically aggressive UTUC tumors. URS low-grade UTUC that becomes upgraded to high-grade might carry a better prognosis than high-grade UTUC on URS. Tumor specific factors are likely to be responsible for upgrading to high-grade on RNU.

International journal of urology : official journal of the Japanese Urological Association. 2022 Nov 09 [Epub ahead of print]

Satoshi Katayama, Benjamin Pradere, Nico C Grossman, Aaron M Potretzke, Stephen A Boorjian, Alireza Ghoreifi, Sia Daneshmand, Hooman Djaladat, John P Sfakianos, Andrea Mari, Zine-Eddine Khene, David D'Andrea, Nozomi Hayakawa, Alberto Breda, Matteo Fontana, Kazutoshi Fujita, Alessandro Antonelli, Thomas van Doeveren, Christina Steinbach, Keiichiro Mori, Ekaterina Laukhtina, Morgan Rouprêt, Vitaly Margulis, Pierre I Karakiewicz, Motoo Araki, Eva Compérat, Yasutomo Nasu, Shahrokh F Shariat

Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., 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, Icahn School of Medicine at Mount Sinai Hospital, New York City, New York, USA., Department of Urology, Careggi Hospital, University of Florence, Florence, Italy., Department of Urology, Hospital Pontchaillou, CHU Rennes, Rennes, France., Department of Urology, St. Marianna University School of Medicine, Kanagawa, Japan., Department of Urology, Fundació Puigvert, Autonoma University of Barcelona, Barcelona, Spain., Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan., Urology Unit AUOI Verona, Department of Surgery, Dentistry, Pediatrics and Gynecology, University of Verona, Verona, Italy., Department of Urology, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, Rotterdam, The Netherlands., GRC 5 Predictive Onco-Uro, AP-HP, Urology, Pitie-Salpetriere Hospital, Sorbonne University, Paris, France., Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas, USA., Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, Quebec, Canada., Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.