Prognostic and Predictive Factors in Advanced Urothelial Carcinoma Treated with Immune Checkpoint Inhibitors: A Review of the Current Evidence

SIMPLE SUMMARY: Despite immune checkpoint inhibitors’ (ICIs) improved overall survival in urothelial carcinoma patients, only a minority of them benefit from immunotherapy. Therefore, there is an unmet clinical need to identify biomarkers which are useful to select the patients who are most likely to respond to ICIs. This review describes the prognostic and predictive role, and potential clinical applicability, of patient- and tumour-related factors. These factors include new molecular classes, tumour mutational burden, mutational signatures, circulating tumour DNA, programmed death-ligand 1, inflammatory indices and clinical characteristics. This summary may help clinicians to assess patients who are considered for ICI treatment, and may drive further prospective research on these biomarkers. ABSTRACT: In recent years, the treatment landscape of urothelial carcinoma has significantly changed due to the introduction of immune checkpoint inhibitors (ICIs), which are the standard of care for second-line treatment and first-line platinum-ineligible patients with advanced disease. Despite the overall survival improvement, only a minority of patients benefit from this immunotherapy. Therefore, there is an unmet need to identify prognostic and predictive biomarkers or models to select patients who will benefit from ICIs, especially in view of novel therapeutic agents. This review describes the prognostic and predictive role, and clinical readiness, of clinical and tumour factors, including new molecular classes, tumour mutational burden, mutational signatures, circulating tumour DNA, programmed death-ligand 1, inflammatory indices and clinical characteristics for patients with urothelial cancer treated with ICIs. A classification of these factors according to the levels of evidence and grades of recommendation currently indicates both a prognostic and predictive value for ctDNA and a prognostic relevance only for concomitant medications and patients’ characteristics.