Circulating Tumor DNA as a Marker of Recurrence Risk in Stage III Colorectal Cancer: The α‐CORRECT Study

BACKGROUND AND OBJECTIVES: Identification of colorectal cancer (CRC) patients at high risk of recurrence could be of substantial clinical use. We evaluated the association of ctDNA status, using a tumor-informed assay, with recurrence-free survival (RFS). METHODS: Stage III CRC patients were enrolled between 2016 and 2020. Tumor tissue and serial (every 3 months for years 1-3, biannually for years 4-5) blood samples were collected. Utilizing whole-exome sequencing and selection of 50-200 variants for tumor informed assays, ctDNA status was determined using plasma cell-free DNA. RESULTS: Of 137 patients enrolled, 124 with 1029 ctDNA results were included in the analyses. Median follow-up was 4.8 years. Plasma ctDNA status was strongly associated with risk of recurrence during the surveillance period (hazard ratio (HR) 49.6, 95% CI: 16.6-148.3; p < 0.0001), and at the postsurgical (HR 9.6, 95% CI: 3.2-29.5) and postdefinitive therapy timepoints (HR: 16.7, 95% CI: 6.9-40.3). The estimated 3-year RFS for ctDNA positive and ctDNA negative patients were, respectively, 54.5% and 96.1% after surgery, and 18.2% and 90.0% after definitive therapy. Multivariable analysis indicated ctDNA but not CEA was strongly prognostic for recurrence. CONCLUSIONS: Our tumor-informed ctDNA assay was strongly prognostic for recurrence in patients with stage III colorectal cancer at all timepoints.