Evaluation of Circulating Tumor DNA for Methylated BCAT1 and IKZF1 to Detect Recurrence of Stage II/Stage III Colorectal Cancer (CRC).

Background: Most recurrences of early-stage colorectal cancer (CRC) detected with current surveillance measures are widespread and incurable. Circulating tumor DNA (ctDNA) may facilitate earlier diagnosis of recurrent CRC and improve cancer-related outcomes. Methods: Plasma from patients undergoing standard surveillance after definitive treatment for stage II/III CRC was assayed with COLVERA and carcinoembryonic antigen (CEA) at a single time-point. Results were correlated with radiographic imaging. Assay performance, including sensitivity and specificity for recurrence, were compared. Impact of potentially confounding variables was also explored. Results: 322 patients were included in the final analysis, and 27 recurrences were documented over a median follow-up period of 15 months. Sensitivity for recurrence was 63% (CI 42.4-80.6) and 48% (CI 28.7-68.1) for COLVERA and CEA (≥5ng/mL), respectively (p=0.046), while specificity was 91.5% (CI 87.7-94.4) and 96.3% (CI 93.4-98.1), respectively (p=0.016). Smoking and age were independent predictors of CEA but not COLVERA positivity. Conclusion: COLVERA was more sensitive but less specific than CEA in detecting recurrent CRC. Short median follow-up may have been responsible for apparent false positives in COLVERA. Studies with serial sampling and longer follow-up are needed to assess whether earlier detection of CRC recurrence translates into clinical benefit. Impact: This prospective study showed that COLVERA ( a two-gene ctDNA assay) was more sensitive for detection of recurrence in a cohort of patients undergoing surveillance after definitive therapy for stages II and III CRC