# Real-world experience of circulating tumor DNA testing in resectable colorectal cancer: a Japanese single-institution observational study

## TL;DR

This study shows that ctDNA testing after colorectal cancer surgery can help predict recurrence risk and guide treatment decisions in real-world clinical settings.

## Contribution

The study provides real-world evidence of ctDNA testing's clinical utility in resectable CRC outside of clinical trials.

## Key findings

- ctDNA-positive patients had a 62.5% recurrence rate, while ctDNA-negative patients had only 13.5%.
- ctDNA clearance after chemotherapy was associated with recurrence-free survival in some patients.
- Persistent ctDNA positivity predicted disease progression.

## Abstract

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 or comorbidities remains unclear. We conducted a prospective observational study to describe the real-world implementation and clinical findings of postoperative ctDNA testing in CRC.

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.

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.

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.