The current role and future directions of circulating tumor cells and circulating tumor DNA in urothelial carcinoma of the bladder.

Urothelial carcinoma of the bladder (UCB) is clinically and genetically a highly heterogeneous disease. Treatment decisions are usually based on histopathological workup and molecular diagnostics on tissue biopsies of the primary tumor or the metastatic site. Next to completely different molecular genotypes of phenotypically similar tumors, standard biopsies do not unconditionally allow real-time insight during the natural course of disease progression. Indeed, in UCB there is an imperative need of biomarkers for improving clinical staging, detecting minimal residual disease, predicting therapy response and prognosis and finally enabling patient stratification for multimodal, individualized treatment and therapy monitoring.Liquid biopsies of blood-based circulating biomarkers have evolved from bench to bedside in some cancer entities. In a narrative review we are summerizing the latest evidence on CTC and ctDNA in muscle-invasive and metastatic UCB. In this review, we summarize the current status, limitations and future needs of circulating tumor cells (CTC) and cell-free circulating tumor DNA (ctDNA) in UCB. Moreover, we discuss the potential clinical application of CTC and ctDNA as prognostic markers at different UCB stages and their value for target therapy guidance. CTC and ctDNA are promising circulating biomarkers in UCB, but none of both has progressed from bench to bedside yet. These markers may support outcome prognostication, patient counseling follow-up monitoring, and potentially decision-making regarding chemotherapy. Further prospective clinical or randomized studies are urgently warranted.