LAUSR

In the era of precision oncology, liquid biopsy techniques, especially the use of plasma circulating tumour DNA (ctDNA) analysis, represent a paradigm shift in the use of genomic biomarkers with considerable implications for clinical practice. Compared with tissue-based tumour DNA analysis, plasma ctDNA is more convenient to test, more readily accessible, faster to obtain and less invasive, minimizing procedure-related risks and offering the opportunity to perform serial monitoring. Additionally, genomic profiles of ctDNA have been shown to reflect tumour heterogeneity, which has important implications for the identification of resistant clones and selection of targeted therapy well before clinical and radiographic changes occur. Moreover, plasma ctDNA testing can also be applied to cancer screening, risk stratification and quantification of minimal residual disease. These features provide an unprecedented opportunity for early treatment of patients, improving the chances of treatment success. Liquid biopsy techniques, especially the use of plasma circulating tumour DNA (ctDNA) analysis, are a convenient, fast and non-invasive approach to the diagnosis and monitoring of urological cancers, and could enable selection of targeted therapy before clinical and radiographic changes occur. In this Review, the authors discuss the uses of liquid biopsy and plasma ctDNA analysis in particular, and consider how it could be used in clinical practice now and in the future. Precision medicine entails the targeting of therapy according to the presence of specific genomic biomarkers; thus, the ability to detect such biomarkers is of paramount importance. Liquid biopsies are non-invasive and fast and can be repeatedly performed throughout a disease course and during treatment to provide information on tumour heterogeneity and to capture the emergence of resistant clones. Circulating tumour DNA (ctDNA) analysis offers the opportunity to identify treatment failures well before clinical and radiographic progression, enabling early interventions and possibly increasing the chances of treatment success. Characterization of a tumour’s genomic landscape using ctDNA analysis can identify predictive biomarkers for patient selection and enrolment in clinical trials. ctDNA yield depends on various factors, including time of blood sample acquisition relative to treatment and response, tumour mutational and disease burden, and the amount of tumour-derived cell-free DNA (cfDNA), which should be considered when ordering and interpreting the test.