Established and emerging biomarkers approaches in urothelial carcinoma.

[INTRODUCTION] Urothelial carcinoma (UC) is marked by significant molecular heterogeneity and this complexity challenges precision medicine. Recent advances have improved biomarker development for UC diagnosis, prognosis and treatment.

[AREAS COVERED] This review discusses established and emerging biomarkers in UC, including FGFR3 and HER2 alterations, PD-L1 expression and circulating tumor DNA (ctDNA). It also summarizes novel biomarkers such as Nectin-4, TROP-2, HER3, tumor mutational burden (TMB), and interferon-gamma signatures. The expanding role of artificial intelligence in biomarker discovery and interpretation is also addressed. Current literature was reviewed by a systematic search using PubMed, focusing on high-impact clinical trials, guidelines and recent reviews published up to May 2025.

[EXPERT OPINION] Despite advances, clinical implementation of biomarkers in UC is limited by methodological inconsistencies and lack of standardization. Robust clinical trials and multi-modal approaches, including liquid biopsy, tissue analysis, and AI-driven tools, will be essential to advance precision oncology in UC.