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Dynamic Circulating Tumor DNA Methylation Monitoring Guiding Postoperative Surveillance in Nonmetastatic Colorectal Cancer: A Prospective, Randomized, Phase III FIND Trial

In brief

ctDNA monitoring doubles curative-intent therapy rate to 48% in post-surgery colorectal cancer

In the phase III FIND trial of 584 patients, ctDNA-guided surveillance raised the proportion receiving curative-intent metastasis-directed treatment from 24% to 48%, with recurrence detected about four months earlier. Recurrence overall was unchanged, and long-term survival benefit remains to be proven.

Journal
Journal of clinical oncology : official journal of the American Society of Clinical Oncology (Q1)
Published
29 July 2026
Study design
Randomized controlled trial
Evidence level
Level 1, High (CEBM 1b)
Authors
Shaobo Mo, Chaoqiang Zhou, Maoguang Ma, Wenqin Luo, Yaqun Li, Ping Lu, et al.
PMID
42525894
DOI
10.1200/JCO-25-03009

Why clinicians should know about it

Abstract

PURPOSE: We hypothesized that a dynamic surveillance strategy guided by circulating tumor DNA (ctDNA) methylation would increase the rate of curative-intent therapy for recurrence in patients with nonmetastatic colorectal cancer (CRC) after curative resection. METHODS: The FIND trial (ClinicalTrials.gov identifier: NCT05904665) is a prospective, multicenter, randomized, phase III study. Patients with nonmetastatic CRC were randomly assigned to ctDNA-guided surveillance or standard computed tomography (CT)-based monitoring. In the ctDNA-guided group, a positive ctDNA result triggered immediate CT imaging; if negative, bimonthly CT continued alongside quarterly ctDNA testing. After two consecutive ctDNA-negative results, imaging reverted to standard frequency. The primary end point was the proportion of patients with recurrence receiving curative-intent metastasis-directed therapy. RESULTS: Among 584 eligible patients (289 ctDNA-guided, 295 control) in the modified intention-to-treat population, with a median follow-up of 23.3 months, recurrence rates were similar (18.0% v 18.6%, P = .919). The ctDNA-guided group had a significantly higher rate of curative-intent treatment (48.1% v 23.6%, relative risk 2.03, P = .008). The median time to clinical recurrence was significantly shorter in the ctDNA-guided group than in the control group (9.5 v 13.4 months; P < .001), representing a lead time of 3.9 months. Among recurrences confined to the liver and/or lungs, the ctDNA-guided group showed higher curative resection rates (42.3% v 18.2%, P = .002). These patients had more favorable hepatic metastatic features: fewer lesions (≤3: 75.0% v 28.6%, P = .005), smaller tumor size (≤3 cm: 90.0% v 57.1%, P = .033), and more unilobar disease (80.0% v 28.6%, P = .002). CONCLUSION: ctDNA methylation-guided dynamic surveillance improves the rate of curative-intent therapy for recurrence in patients with initially nonmetastatic CRC through earlier detection of resectable metastases, pending validation of long-term survival benefit in future analyses with mature data.

Abstract as published, via PubMed.

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For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.