Comprehensive characterization of cell-free tumor DNA in plasma and urine of patients with renal tumors.

Cell-free tumor-derived DNA (ctDNA) allows non-invasive monitoring of cancers, but its utility in renal cell cancer (RCC) has not been established.

Here, a combination of untargeted and targeted sequencing methods, applied to two independent cohorts of patients (n = 91) with various renal tumor subtypes, were used to determine ctDNA content in plasma and urine.

Our data revealed lower plasma ctDNA levels in RCC relative to other cancers of similar size and stage, with untargeted detection in 27.5% of patients from both cohorts. A sensitive personalized approach, applied to plasma and urine from select patients (n = 22) improved detection to ~ 50%, including in patients with early-stage disease and even benign lesions. Detection in plasma, but not urine, was more frequent amongst patients with larger tumors and in those patients with venous tumor thrombus. With data from one extensively characterized patient, we observed that plasma and, for the first time, urine ctDNA may better represent tumor heterogeneity than a single tissue biopsy. Furthermore, in a subset of patients (n = 16), longitudinal sampling revealed that ctDNA can track disease course and may pre-empt radiological identification of minimal residual disease or disease progression on systemic therapy. Additional datasets will be required to validate these findings.

These data highlight RCC as a ctDNA-low malignancy. The biological reasons for this are yet to be determined. Nonetheless, our findings indicate potential clinical utility in the management of patients with renal tumors, provided improvement in isolation and detection approaches.

Genome medicine. 2020 Feb 28*** epublish ***

Christopher G Smith, Tina Moser, Florent Mouliere, Johanna Field-Rayner, Matthew Eldridge, Anja L Riediger, Dineika Chandrananda, Katrin Heider, Jonathan C M Wan, Anne Y Warren, James Morris, Irena Hudecova, Wendy N Cooper, Thomas J Mitchell, Davina Gale, Andrea Ruiz-Valdepenas, Tobias Klatte, Stephan Ursprung, Evis Sala, Antony C P Riddick, Tevita F Aho, James N Armitage, Samantha Perakis, Martin Pichler, Maximilian Seles, Gabriel Wcislo, Sarah J Welsh, Athena Matakidou, Tim Eisen, Charles E Massie, Nitzan Rosenfeld, Ellen Heitzer, Grant D Stewart

Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK. ., Medical University of Graz, Diagnostic and Research Center for Molecular Biomedicine, Institute of Human Genetics, Graz, Austria., Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081, HV, Amsterdam, The Netherlands., Cambridge Urology Translational Research and Clinical Trials Office, University of Cambridge, Cambridge, CB2 0QQ, UK., Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK., Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK., Department of Surgery, University of Cambridge, Cambridge, CB2 0QQ, UK., Cancer Research UK Major Centre - Cambridge, Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK., Department of Internal Medicine Graz, Austria Division of Oncology, Medical University of Graz, Graz, Austria., Department of Urology, Medical University of Graz, Graz, Austria., Department of Oncology, Military Institute of Medicine, Warsaw, Poland., Hutchison/MRC Research Centre, University of Cambridge, Cambridge, CB2 0QQ, UK., Medical University of Graz, Diagnostic and Research Center for Molecular Biomedicine, Institute of Human Genetics, Graz, Austria. ., Cancer Research UK Major Centre - Cambridge, Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK. .