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.