Clinicopathological characteristics of patients with minimal residual disease in stage II–III colon cancer: Interim results from the observational cohort of CLAUDIA study.

Abstract

3635 Background: Circulating tumor DNA (ctDNA) monitoring for minimal residual disease (MRD) has emerged as a key prognostic biomarker in resected colon cancer. The CLAUDIA study (KCSG CO22-12, NCT05534087) is a prospective, multicenter study evaluating ctDNA-guided adjuvant therapy. It includes an observational screening cohort (Part 1) and a randomized interventional trial for MRD (+) patients (Part 2). Here, we report the baseline characteristics and MRD status of the Part 1 cohort and the clinical outcomes for patients who did not participate in Part 2. Methods: In Part 1, stage II or III colon cancer patients who received curative resection scheduled for adjuvant oxaliplatin-based chemotherapy (FOLFOX or CAPOX) are enrolled (N= approximately 1,200). Postoperative plasma samples collected after surgery, before starting adjuvant chemotherapy, are analyzed using a tumor-informed ctDNA assay that tracks up to 100 patient-specific mutations (IMBdx). Patients identified as MRD (+) are screened for a Part 2 randomized phase III trial (N=236) comparing mFOLFIRINOX to standard care. MRD (-) patients are managed at the investigator’s discretion. Results: As of November 2025, a total of 809 patients were enrolled. Postoperative ctDNA was positive in 228 patients (28.2%). MRD (+) rate was significantly higher in patients with T4 tumors (40.5% vs. 22.8% in T1–3 tumors, p<0.0001), N2 disease (38.8% vs. 25.4% in N0–1, p=0.0007), and elevated postoperative CEA (>5 ng/mL) (42.2% vs. 26.8% in normal, p=0.013). Accordingly, MRD (+) was enriched in high-risk stage III disease (T4 or N2) (40.3% vs. 21.5% in low-risk stage III and stage II, p<0.0001). However, MRD (+) rates did not differ significantly by histology, tumor location, or MSI status. MRD positivity was not associated with the mutational status of the frequently altered genes in colon cancer (APC, TP53, KRAS, BRAF, ERBB2, SMAD4). We analyzed outcomes in 673 patients who did not participate in the Part 2 randomized study [92 MRD (+) and 581 MRD (-)]. In the multivariate analysis of recurrence-free survival adjusting for clinicopathologic covariates, MRD (+) was the strongest independent predictor of poor outcome (adjusted HR 5.81; 95% CI 2.65–12.74; p<0.0001). Conclusions: Postoperative ctDNA status serves as a robust prognostic biomarker in stage II-III colon cancer, correlating with advanced tumor burden. MRD (+) patients who receive standard-of-care management face a significantly increased risk of recurrence. These findings validate the utility of the ctDNA assay used and support the rationale for the ongoing CLAUDIA Part 2 trial, which investigates treatment intensification for MRD (+) patients. Clinical trial information: NCT05534087 .