DOI: 10.1001/jamaoncol.2026.4196 ISSN: 2374-2437

FGFR Alterations in Bladder Cancer—From Molecular Pathogenesis to Precision Oncology

Katrina Collins, Liang Cheng
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Importance

Alterations in the fibroblast growth factor receptor (FGFR) pathway, particularly FGFR3 , are among the most common genomic events in urothelial carcinoma (UC) and represent a cornerstone of precision oncology. Although FGFR3 alterations predominate, selected FGFR2 fusions also identify patients who may benefit from targeted therapy. This review summarizes the biology, molecular diagnostics, and evolving clinical applications of FGFR alterations in UC.

Observations

FGFR2/3 alterations are clinically actionable biomarkers across non–muscle-invasive, muscle-invasive, metastatic, and upper-tract UC. Comprehensive genomic profiling, tissue sequencing, plasma circulating tumor DNA, urine-based molecular assays, and molecular residual disease assessment are expanding their roles in diagnosis, treatment selection, surveillance, and disease monitoring. Recent clinical studies support combination strategies, next-generation FGFR inhibitors, and earlier use of FGFR-directed therapy, while emerging technologies, including artificial intelligence–assisted pathology and integrated multi-omic biomarkers, may further improve patient selection.

Conclusions and Relevance

FGFR alterations have become integral to the molecular classification and precision management of UC. Continued advances in molecular diagnostics, liquid biopsy, biomarker-guided therapy, and next-generation FGFR inhibitors are expected to further personalize care. This review provides a practical framework for integrating FGFR biomarkers into contemporary management and highlights emerging developments likely to influence future clinical practice.

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