Current and Future Role of Circulating DNA in the Diagnosis and Management of Urothelial Carcinoma.

The growing sophistication of tumor molecular profiling has helped to slowly transition oncologic care toward a more personalized approach in different tumor types, including in bladder cancer. The National Comprehensive Cancer Network recommends that all patients with stage IVA and stage IVB urothelial carcinoma have molecular analysis that integrates at least FGFR3 testing to help facilitate the selection of future therapeutic options. Sequencing of tumor-derived tissue is the mainstay to obtain this genomic testing, but as in other cancers, there has been extensive research into the integration of liquid biopsies in longitudinal management. Liquid biopsies broadly refer to the isolation of both cellular and noncellular tumor components including proteins and nucleic acids such as mRNA and circulating free DNA within a liquid sample. Although protein-based testing and testing of circulating tumor cells are options, the bulk of promising research in bladder cancer is investigating the role of plasma-based circulating tumor DNA (ctDNA). Currently, a universal consensus on optimal preanalytic and analytic approaches has not been fully defined, and the exact role that liquid biopsies should have in screening, diagnosis, prognostication, treatment selection, and monitoring is not yet known. Still, it can be expected that ctDNA testing will be a part of appropriate management of muscle-invasive bladder cancer and metastatic bladder cancer in the near future. In this review, the goal is to provide a practical overview of the current and future role of ctDNA in bladder cancer including ongoing trials.