Real-World Experience of Circulating Tumor DNA Testing in Resectable Colorectal Cancer: A Japanese Single-Institution Observational Study.

Background: Assessment of molecular residual disease (MRD) using circulating tumor DNA (ctDNA) is a powerful prognostic tool for detecting postoperative recurrence in colorectal cancer (CRC). However, ctDNA-based MRD testing has been available only within clinical trials in Japan, and its clinical utility in patients ineligible for trials due to age orcomorbidities remains unclear. We conducted a prospective observational study to describe the real-world implementation and clinical findings of postoperative ctDNA testing in CRC. Methods: CRC patients who underwent tumor-agnostic ctDNA MRD testing after curative-intent resection were prospectively enrolled. When ctDNA was detected, early imaging was performed to assess recurrence. Clinical outcomes were analyzed according to ctDNA status. Results: 56 CRC patients who underwent ctDNA testing 4-8 weeks after surgery between June 2023 and June 2025 were analyzed. 18 (32.1%) were ctDNA-positive and 38 (67.9%) were ctDNA-negative. Radiological recurrence occurred in 10 of 16 evaluable ctDNA-positive patients (62.5%), including liver metastases in 4 and no lung metastases. In contrast, recurrence was observed in 5 of 37 ctDNA-negative patients (13.5%), including lung metastases in 3 and no liver metastases. Three ctDNA-positive patients (18.8%) achieved ctDNA clearance after adjuvant chemotherapy and remained recurrence-free, whereas persistent-ctDNA positivity predicted disease progression. In the ctDNA-negative cohort, 84.5% remained disease-free regardless of adjuvant therapy. Conclusions: This interim report demonstrates the feasibility of implementing postoperative ctDNA testing in real-world clinical practice. While exploratory and descriptive in nature, the findings suggest that ctDNA status may reflect recurrence risk and provide useful information for postoperative management in resectable CRC.