Invasiveness of Upper Tract Urothelial Carcinoma: Clinical Significance and Integrative Diagnostic Strategy

Bokyung Ahn; Doeun Kim; Kye Jin Park; Ja-Min Park; Sun Young Yoon; Bumsik Hong; Yong Mee Cho; Deokhoon Kim

doi:10.4143/crt.2023.1150

Invasiveness of Upper Tract Urothelial Carcinoma: Clinical Significance and Integrative Diagnostic Strategy

Cancer Res Treat. 2023 Dec 18. doi: 10.4143/crt.2023.1150. Online ahead of print.

Authors

Bokyung Ahn¹, Doeun Kim², Kye Jin Park³, Ja-Min Park¹, Sun Young Yoon¹, Bumsik Hong⁴, Yong Mee Cho¹, Deokhoon Kim¹

Affiliations

¹ Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
² Department of Medical Science, Biomedical Science, University of Ulsan College of Medicine, Seoul, Korea.
³ Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
⁴ Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

PMID: 38147818
DOI: 10.4143/crt.2023.1150

Abstract

Purpose: In this study, we aimed to determine the clinicopathologic, radiologic, and molecular significance of the tumor invasiveness to further stratify the patients with high-grade (HG) upper tract urothelial carcinoma (UTUC) who can be treated less aggressively.

Materials and methods: Clinicopathologic and radiologic characteristics of 166 surgically resected HG UTUC (48 non-invasive, and 118 invasive) cases were evaluated. Six non-invasive UTUC cases with intra-tumoral tumor grade heterogeneity were selected for whole exome sequencing (WES) to understand the underlying molecular pathophysiology. Barcode-tagging sequencing (BTSeq) was done for validation of the target genes from WES data.

Results: Patients with non-invasive UTUC showed no cancer-specific death with better cancer-specific survival (p<0.001) and recurrence-free survival (p<0.001) compared to the patients with invasive UTUC. Compared to the invasive UTUC, non-invasive UTUC was correlated to a low grade on the preoperative abdominal computed tomography (CT) grading system (p<0.001), histologic intratumoral tumor grade heterogeneity (p=0.018), discrepancy in preoperative urine cytology diagnosis (p=0.018), and absence of urothelial carcinoma in situ (p<0.001). WES of the heterogeneous components showed mutually shared HRAS and FGFR3 mutations shared between the HG and LG components. HRAS mutation was associated with the lower grade on preoperative abdominal CT and intratumoral tumor grade heterogeneity (p=0.045 and p<0.001, respectively), whereas FGFR3 mutation was correlated to the absence of carcinoma in situ (p<0.001).

Conclusion: According to our comprehensive analysis, HG non-invasive UTUC can be preoperatively suspected based on distinct preoperative radiologic, cytologic, histologic, and molecular features. Non-invasive HG UTUC shows excellent prognosis and thus should be treated less aggressively.

Keywords: Barcode-tagged sequencing; Invasive urothelial carcinoma; Non-invasive urothelial carcinoma; Upper tract urothelial carcinoma; Whole-exome sequencing.