Utility of Circulating Tumor DNA Monitoring in Postnephrectomy Renal Cancer

PURPOSE Increased heterogeneity in outcomes has been observed postnephrectomy in patients with renal cell carcinoma (RCC), with standard clinical parameters being primarily used for risk assessment. Currently, no blood-based biomarkers are available for molecular residual disease (MRD) detection in RCC. Herein, we performed a multicenter, real-world evaluation of the prognostic value of circulating tumor DNA (ctDNA) in resected RCC. METHODS This real-world evidence-based multi-institutional study included a cohort of 77 patients with stage I-IV RCC. Longitudinal ctDNA testing was performed on plasma samples (n = 295) using a clinically validated, personalized, tumor-informed ctDNA assay (Signatera, Natera, Inc, Austin, TX). ctDNA results were analyzed, and association with recurrence-free survival was assessed. RESULTS The patient cohort included 77 patients with stage I-IV RCC (clear cell: 64, non–clear cell: 13). Patients who tested ctDNA-positive during the MRD window experienced worse prognosis and a higher likelihood of recurrence (hazard ratios, 18; P < .0001) compared with their ctDNA-negative counterparts. CONCLUSION Overall, we demonstrate the utility of ctDNA testing for MRD detection. Future prospective studies in RCC would be needed to validate the utility of ctDNA in informing clinical decision making.