Clinicopathological Features of FGFR3 - Mutated Upper Tract Urothelial Carcinoma: A Genomic Database Analysis

Upper tract urothelial carcinomas (UTUCs) arise in the renal pelvis or the ureter, accounting for approximately 5% of all urothelial carcinomas. Recent years have witnessed the publication of several studies aimed at assessing the molecular, biologic, and clinical features of UTUC, reporting that FGFR3 mutations are the most observed genetic aberrations; however, several knowledge gaps persist in the understanding of the genomic landscape of this genitourinary malignancy with few treatment options.

In the current study, we aimed to comprehensively analyze clinicopathological features of FGFR3-mutated UTUCs patients in public datasets to increase the current knowledge of the molecular and biologic profile of UTUC. Data regarding clinical outcomes, mutational profiles, and copy number alterations in patients affected by UTUC were downloaded from the cBioPortal for Cancer Genomics Database. UTUC data were available from 4 studies, for a total number of 358 patients; among these, 150 UTUC patients presented FGFR3 mutations.

The current database analysis of the mutational profile of 150 FGFR3-mutated UTUCs suggested that FGFR3 mutations may represent a prognostic factor in this disease, with a statistically longer overall survival compared to wild-type patients treated with radical surgery. In addition, FGFR3 mutations were more frequent in low-grade UTUCs with early-stage disease (pT1, pT2, and pT3).

Genomic characterization of UTUC is destined to become increasingly important, and more efforts aimed at implementing UTUC genomics analysis are warranted.