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

ABSTRACT 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.