The therapeutic and prognostic implications of molecular biomarkers in urothelial carcinoma

Urothelial cell carcinoma (UCC) of the bladder and upper urinary tract is a heterogeneous disease with distinct biologic features resulting in different clinical behaviors. Bladder cancer (BC) is classified into non-muscle invasive BC (NMIBC) and muscle invasive BC (MIBC). NMIBC is associated with high recurrence rates and risk of progression to invasive disease, whereas MIBC is complicated by systemic recurrence after radical cystectomy because of the limited efficacy of available therapies. UCC of the upper urinary tract (UUT-UCC) is a rare but aggressive urologic cancer characterized by multifocality, local recurrence, and metastasis. Conventional histopathologic evaluation of UCC, including tumor stage and grade, cannot accurately predict the behavior of BC and UUT-UCC. Recent clinical and preclinical studies aimed at understanding the molecular landscape of UCC have provided insight into molecular subtyping, inter- or intratumoral heterogeneity, and potential therapeutic targets. Combined analysis of molecular markers and standard pathological features may improve risk stratification and help monitor tumor progression and treatment response, ultimately improving patient outcomes. This review discusses prognostic and therapeutic biomarkers for BC and UUT-UCC, and describes recent advances in molecular stratification that may guide prognosis, patient stratification, and treatment selection.