Immune checkpoint inhibitors in urothelial carcinoma: a practical framework for patient selection, toxicity management, response assessment, and treatment sequencing

INTRODUCTION: Managing urothelial carcinoma with immune checkpoint inhibitors requires addressing issues beyond clinical outcomes. Implementation difficulties affect most patients, predictive biomarkers show limited utility, and treatment discontinuation from toxicity remains problematic. AREAS COVERED: This article integrates clinical trials, systematic reviews, health-system evaluations, and guidelines from 2016 to 2025. We detail limitations of programmed death-ligand 1 (PD-L1) expression, panel-based tumor mutational burden (TMB), clinic-ready toxicity pathways, immune-appropriate response criteria (iRECIST), pseudoprogression, hyperprogression, post-ICI sequencing (FGFR3 alterations, enfortumab vedotin-based therapy, chemotherapy, trials), and delivery models (navigation, electronic patient-reported outcomes, telemedicine, payment structures). EXPERT OPINION: Optimizing systemic frameworks for immunotherapy care requires careful evaluation of functional status, protocols for immune-related adverse events management, standardization for assessments of clinical responses, and ensuring equitable access to care. ctDNA and AI-assisted radiomics are promising adjuncts to clinical care, but still require multi-center prospective validation before adoption into routine practice.