Reflex somatic testing for the detection of FGFR alterations in urinary tract carcinomas: A dual-institutional...

To describe the prevalence and clinicopathologic associations of FGFR-altered urinary tract carcinomas in institutions incorporating reflex testing.

Next-generation sequencing was prospectively performed on urinary tract carcinomas for the detection of FGFR1-4 alterations at 2 tertiary care centers (2021-2025), using the Oncomine Comprehensive Assay (OCA) v3 DNA and OCA Plus RNA. Reflex testing was conducted on metastatic and/or advanced (pT3/4) carcinomas.

The cohort included 366 patients (239 lower tract carcinomas, 72 upper tract carcinomas, and 55 metastases). Median age was 72.5 years (range, 36-97). Fifty-nine (16.1%) tumors were FGFR-altered. Forty-nine (13.4%) patients with actionable FGFR alterations (33 FGFR3 mutations, 13 FGFR3 fusions, and 3 FGFR2 mutations) were all 55 years or older (P = .097). The prevalence of actionable FGFR alterations was significantly higher in upper vs lower tract carcinomas (23.8% vs 13.8%, P = .007) and in lung metastases vs other metastatic sites (57.1% vs 10.4%, P = .002). A higher frequency was also seen in metastases vs primary tumors (16.4% vs 12.9%), although this difference did not reach statistical significance (P = .482). Actionable FGFR alterations were observed in urothelial carcinoma not otherwise specified (40/261) and in urothelial carcinoma with squamous differentiation (6/43), micropapillary features (2/11), or nested features (2/7).

The detection rate for FGFR1-4 alterations in a real-world, dual-institution cohort of urinary tract carcinomas was reported.