Curr Opin Urol. 2026 Mar 6. doi: 10.1097/MOU.0000000000001387. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: Personalised medicine has rapidly reshaped the management of urothelial carcinoma, driven by advances in tumour genomics, immune profiling and targeted drug development. This review is timely as multiple biomarker-driven therapies have recently entered routine clinical practice across disease stages, necessitating an integrated appraisal of how precision approaches should be applied and sequenced in contemporary care.

RECENT FINDINGS: Key advances include the expanding role of immune biomarkers beyond PD-L1, such as tumour mutational burden and DNA damage response alterations, to refine the use of immune checkpoint inhibitors. FGFR3 alterations represent the first validated genomic target in urothelial carcinoma, with FGFR inhibitors now established treatment options. Antibody-drug conjugates targeting Nectin-4 and HER2 have demonstrated substantial clinical activity, redefining treatment paradigms in both first-line and refractory settings. In parallel, circulating tumour DNA has emerged as a powerful dynamic biomarker for minimal residual disease detection and adjuvant treatment selection.

SUMMARY: Urothelial carcinoma has transitioned into a biomarker-driven disease, enabling more precise, biologically informed treatment decisions. Integrating genomic, immunologic and liquid biopsy biomarkers will be essential to optimise patient selection, treatment sequencing and toxicity management, and represents a critical direction for future research and clinical practice.

PMID:41827087 | DOI:10.1097/MOU.0000000000001387