Circulating tumor DNA in the surveillance of patients with oligometastatic renal cell carcinoma treated with stereotactic ablative radiation.

Abstract

477 Background: Oligometastatic renal cell carcinoma (oRCC) patients receiving stereotactic ablative radiation (SAbR) are in need of effective biomarkers beyond imaging to identify those most likely to fail rapidly and therefore would benefit from systemic therapy. Detection of minimal residual disease (MRD) using circulating tumor (ctDNA) is a promising tool to guide decisions in the management of solid tumors. Herein, we investigate the utility of longitudinal ctDNA monitoring to identify high-risk patients. Methods: Patients with oRCC on surveillance after previous SAbR were enrolled in a prospective registry study and longitudinal quantitative ctDNA testing were performed using a tumor-informed commercial ctDNA assay (Signatera). Disease progression was assessed using standard-of-care clinical / radiographic exams and compared to the ctDNA levels that were obtained within the median 32.5 days (IQR 18.5-59) of radiographic exams. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated. Results: The cohort encompassed 17 patients with oRCC (16/17 metachronous >1 year after nephrectomy) who underwent 42 ctDNA measurements between September 2022 and August 2023 with a median of 3 (range 2-6) ctDNA time points per patient. Median follow up after start of ctDNA monitoring was 10.3 months. Seven patients developed radiographic progression at new sites including 6 who received additional SAbR and one who started systemic therapy with interleukin-2. At most recent follow up, 13/17 patients had no radiographic evidence of disease. Out of the 42 ctDNA time points, 11 had detectable ctDNA and 17 had clinical/radiographically detectable metastasis. The sensitivity, specificity, PPV, and NPV were calculated to be 64.7%, 100.0%, 100.0%, and 80.6% respectively. Out of 6 patients who underwent had ctDNA testing on SAbR, 5 had undetectable levels and the only patient that had detectable ctDNA levels showed a robust decline in ctDNA levels post SAbR. In the interleukin-2 treated patient, detectable levels of ctDNA became undetectable post treatment which also correlated with a complete radiographic response. Conclusions: This study highlights the utility of ctDNA as a prognostic biomarker in the surveillance of oRCC patients who were previously treated with SAbR. A high SPE and PPV suggests that rising ctDNA levels may harbinger radiographic progression requiring systemic therapy intervention. A larger study is warranted to further validate the findings of this study and to optimally integrate ctDNA kinetics to direct subsequent treatment choices for the oRCC patients.