Cancer Research and Treatment

Original Article

Genitourinary cancer

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; Cancer Res Treat. 2024;56(3):856-870. Published online December 18, 2023; DOI: https://doi.org/10.4143/crt.2023.1150

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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 noninvasive, and 118 invasive) cases were evaluated. Six noninvasive UTUC cases with intratumoral tumor grade heterogeneity were selected for whole-exome sequencing (WES) to understand the underlying molecular pathophysiology. Barcode-tagging sequencing was done for validation of the target genes from WES data.
Results
Patients with noninvasive 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, noninvasive UTUC was correlated to a low grade (LG) 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 noninvasive UTUC can be preoperatively suspected based on distinct preoperative radiologic, cytologic, histologic, and molecular features. Noninvasive HG UTUC shows excellent prognosis and thus should be treated less aggressively.

Citations

Citations to this article as recorded by

Papillary renal neoplasm with reverse polarity shows benign behavior: Results from a 77-case clinicopathological and molecular study
Yong Il Lee, Ja-Min Park, Sun Young Yoon, Cheryn Song, Yong Mee Cho
Annals of Diagnostic Pathology.2026; 80: 152498. CrossRef
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American Journal of Clinical Pathology.2024;[Epub] CrossRef
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BMC Cancer.2024;[Epub] CrossRef

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