Circulating and urinary tumour DNA in urothelial carcinoma - upper tract, lower tract and metastatic disease

Non-invasive liquid biopsies such as plasma circulating tumour DNA (ctDNA) and urinary tumour DNA (utDNA) are promising tools for urothelial carcinoma diagnosis and management. In this Review, the authors provide an overview of the different liquid biopsy technologies available, and discuss the current state as well as future perspectives of ctDNA and utDNA application in urothelial carcinoma clinical care. Precision medicine has transformed the way urothelial carcinoma is managed. However, current practices are limited by the availability of tissue samples for genomic profiling and the spatial and temporal molecular heterogeneity observed in many studies. Among rapidly advancing genomic sequencing technologies, non-invasive liquid biopsy has emerged as a promising diagnostic tool to reproduce tumour genomics, and has shown potential to be integrated in several aspects of clinical care. In urothelial carcinoma, liquid biopsies such as plasma circulating tumour DNA (ctDNA) and urinary tumour DNA (utDNA) have been investigated as a surrogates for tumour biopsies and might bridge many shortfalls currently faced by clinicians. Both ctDNA and utDNA seem really promising in urothelial carcinoma diagnosis, staging and prognosis, response to therapy monitoring, detection of minimal residual disease and surveillance. The use of liquid biopsies in patients with urothelial carcinoma could further advance precision medicine in this population, facilitating personalized patient monitoring through non-invasive assays.