Longitudinal detection of circulating tumor DNA in patients with advanced renal cell carcinoma.

715 Background: Treatment response monitoring is key to effective disease management for patients with advanced (RCC) and can potentially improve clinical outcomes. Circulating tumor DNA (ctDNA) has shown promise as a biomarker in the early identification of treatment response in a variety of tumor types. Herein, we evaluated ctDNA-derived molecular residual disease (MRD) detection and dynamics in both clear cell (ccRCC) and non-clear cell (nccRCC) RCC patients treated with standard of care therapy and provide correlations with clinical outcomes. Methods: This was a multi-center retrospective analysis of real-world data obtained from commercial ctDNA testing (Signatera, Natera, Inc.), 41 patients (142 plasma samples) with high-risk resected or metastatic RCC were analyzed for ctDNA. Clinical data were collected on IMDC risk category, pathologic subtype, tumor stage and grade including the presence of sarcomatoid/rhabdoid features. Progression on radiological imaging was based on RECIST 1.1. criteria. Results: Of the 41 patients, 73% (30/41) had ccRCC and the remaining 27% (11/41) were nccRCC. Immunotherapy was administered as a single agent or in combination with other immune checkpoint inhibitor agents/targeted therapy in 78% (32/41) in either frontline or refractory settings. ctDNA detection at any time point was 70% (29/41) and patients were followed-up for a median of 26.4 weeks (range: 0.9-90.6) from the first ctDNA time point. Fourteen patients (34%) experienced disease progression during follow-up and all had ctDNA detected ahead of radiological progression (100% sensitivity) with a median lead time of 13.6 weeks (range: 1-39.7 weeks). Concordance between clinical outcome and ctDNA status (detected or not detected) was observed in 78% (32/41) of the patients, 12% (5/41) showed discordance, and imaging data is pending for 10% (4/41) at the time of analysis. Conclusions: Collectively, our study demonstrates high concordance between MRD status and subsequent clinical outcomes. MRD had 100% sensitivity for predicting subsequent radiographic progression with significant median lead time. MRD may serve as a valuable tool for monitoring patients on immunotherapy-based regimens for RCC.