Towards biomarker-driven therapies for urothelial carcinoma

Abstract

Molecularly targeted agents and immune checkpoint inhibitors (ICIs) are transforming the treatment landscape for patients with advanced-stage urothelial carcinoma (aUC), although trials testing these novel agents have shown mixed results. In this context, the identification of biomarkers has seen limited success: while activating mutations in FGFR3 are now established as an actionable biomarker to guide treatment with FGFR inhibitors, PD-L1 expression has shown inconsistent value as a predictive biomarker of response to ICIs. The identification of prognostic and predictive biomarkers for ICIs, antibody-drug conjugates and targeted therapies is an active area of research; promising candidates include tumour mutational burden and HER2 overexpression. In the past few years, circulating tumour DNA has emerged as a minimally invasive biomarker, with increasing data supporting its prognostic value and utility for monitoring clinical responses. In this Review, we address these developments and discuss biomarkers that could have clinical utility in patients with aUC.