What question did this study set out to answer?

This research aims to explore the relevance of bladder cancer subtyping for upper-tract urothelial carcinoma (UTUC) and identify possible racial differences in tumor characteristics.

April 5, 2026

Abstract 3885: Application of transcriptomic bladder-cancer subtypes to upper-tract urothelial carcinoma (UTUC) across international cohorts reveals racial differences and translational limitations.

Key Points

This research aims to explore the relevance of bladder cancer subtyping for upper-tract urothelial carcinoma (UTUC) and identify possible racial differences in tumor characteristics.
Retrospective collection of FFPE UTUC nephroureterectomy specimens from two medical centers.
Conducted RNA sequencing on 126 tumors classified using consensus-MIBC and UROMOL2021-NMIBC frameworks.
Estimated event-free survival (EFS) using Kaplan-Meier analysis.
Majority of UTUC tumors (54.8%) were identified as non-muscle-invasive (NMI), with luminal-papillary subtype being predominant.
Significant differences in subtype distributions between Cedars-Sinai (Western) and Kindai (Asian) cohorts.
Pathologic T stage was the strongest prognostic factor for EFS, overshadowing molecular subtype effects.

Abstract

Abstract Background and Objectives: Management of UTUC follows bladder cancer (BC) guidelines but could be refined. Molecular subtyping has yielded valuable insights into tumor biology and therapy response/resistance for muscle-invasive (MI) and non-MI (NMI) BC and could have similar value for UTUC. Like NMIBC, UTUC is predominantly luminal-papillary (LumP) in subtype, which has spurred more granular UTUC-specific classification schemes. Here, we investigated whether MIBC and NMIBC subtyping could be translated to UTUC. Methods: Histologically confirmed FFPE UTUC nephroureterectomy specimens were retrospectively collected from Cedars-Sinai Medical Center (Los Angeles, USA) and Kindai University (Osaka, Japan). RNA-seq was performed on 126 tumors, which were classified using consensus-MIBC and UROMOL2021-NMIBC frameworks. Event-free survival (EFS) was estimated by Kaplan-Meier analysis, excluding cases with prior or concurrent BC. Results: Of 126 UTUCs, 69 (54.8%) were NMI and 55 (47.3%) MI. The LumP subtype was most common (57%), enriched in NMI-UTUC (75%) versus MI-UTUC (36%), mirroring NMIBC vs. MIBC. Cedars-Sinai tumors were mainly NMI (59%), while Kindai tumors were mostly MI (58%), suggesting population differences. LumP enrichment in Cedars-Sinai (80% of NMI vs. 33% of MI) contrasted with more balanced distributions in Kindai (5/10 NMI, 7/15 MI), indicating potential race-specific variation.Within LumP-UTUC, all four UROMOL classes were represented, whereas non-LumP UTUCs were mostly UROMOL 2b. Stratification by LumP vs. other revealed opposing (but not significant) survival trends in NMI- and MI-UTUC: LumP had poorer 5-year EFS in NMI-UTUC but better outcomes in MI-UTUC. Further stratification of LumP NMI-UTUC by UROMOL class showed no significant EFS differences, although Class 2b tumors had comparably poor outcomes to LumP MI-UTUC. Pathologic T stage remained the strongest prognostic factor (EFS: Ta T1 T2 T3/4; p 0.05). Conclusions: LumP prevalence in UTUC is largely driven by NMI tumors, recapitulating NMIBC biology. Subtype and stage distributions vary between Western and Asian cohorts, implying race-related molecular diversity. While BC-derived classifiers can categorize UTUC, their clinical interpretation does not directly translate. Tumor stage outweighs molecular subtype as the principal determinant of outcome. Citation Format: Joshua M. Scurll, Henning Bahlburg, Tran Anh Thu (Wendy) Phung, John Heard, Mamoru Hashimoto, Kazutoshi Fujita, Daniel Luthringer, Toru Sakatani, Kaoru Murakami, Charles J. Rosser, Ewan A. Gibb, Peter C. Black1, Hideki Furuya. Application of transcriptomic bladder-cancer subtypes to upper-tract urothelial carcinoma (UTUC) across international cohorts reveals racial differences and translational limitations abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3885.

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