Emerging Roles of Urine-Derived Components for the Management of Bladder Cancer: One Man’s Trash Is Another Man’s Treasure

SIMPLE SUMMARY: Urinary bladder cancer (UBC) is one of the most common and deadly cancers worldwide, with many patients not responding to chemotherapy, or presenting with serious adverse effects after chemotherapy. Yet, current bench side assays provide limited accuracy for predicting therapeutic response to chemotherapeutic drugs. The aim of this review is to demonstrate the potential of urinary-derived extracellular vesicles and UBC-organoids to serve as predictive biomarkers for this cancer. Specifically, molecular subtyping of urine-derived extracellular vesicles has the potential to provide insights into the molecular stratification of the tumor, while urinary organoids will allow for individualized chemotherapy testing in the context of precision medicine. ABSTRACT: Urinary bladder cancer (UBC) is the most common malignancy of the urinary tract in humans, with an estimated global prevalence of 1.1 million cases over 5 years. Because of its high rates of recurrence and resistance to chemotherapy, UBC is one of the most expensive cancers to treat, resulting in significant health care costs. The development of innovative molecular and cellular tools is necessary to refine patient stratification and help predict response to treatment. Urine is an underused resource of biological components shed from bladder tumors, such as exfoliated cells and extracellular vesicles, that could serve as molecular fingerprints and provide valuable biological insights into tumor phenotype and mechanisms of resistance to chemotherapy. Additionally, characterization of urine-derived extracellular vesicles and cells could be used as reliable biomarkers for prediction of response to neoadjuvant therapy.