Dynamic surveillance using circulating tumor DNA (ctDNA) methylation testing after curative-intent surgery significantly increased the proportion of patients with recurrent nonmetastatic colorectal cancer who were able to undergo curative-intent treatment, according to results of the phase III FIND trial reported by Mo et al in the Journal of Clinical Oncology.
Study Details
The prospective, multicenter, randomized study enrolled patients with stage I to III colorectal cancer who had undergone R0 resection. Patients were randomly assigned to either standard postoperative surveillance or a ctDNA-guided surveillance strategy. In the experimental arm, plasma ctDNA methylation was assessed preoperatively, within 1 month after surgery, and every 3 months for 2 years. A positive ctDNA result triggered immediate contrast-enhanced computed tomography (CT) imaging; if imaging remained negative, patients underwent CT every 2 months while continuing quarterly ctDNA testing until two consecutive negative ctDNA results allowed a return to standard imaging intervals.
Between May 2023 and July 2024, 795 patients were screened across six centers in China, and 728 were randomly assigned. After exclusions, the modified intention-to-treat population included 584 patients: 289 in the ctDNA-guided group and 295 in the standard surveillance group. Median follow-up at the time of analysis was 23.3 months, and the primary endpoint was the proportion of patients with disease recurrence who received curative-intent metastasis-directed therapy.
Key Results
Overall recurrence rates were similar between groups (18.0% in the ctDNA-guided group vs 18.6% with standard surveillance, P = .919). However, among patients who developed recurrence, nearly half of those in the ctDNA-guided arm underwent curative-intent metastasis-directed therapy compared with fewer than one-quarter in the control arm (48.1% vs 23.6%, relative risk = 2.03, 95% confidence interval = 1.19–3.57, P = .008). In addition, postrecurrence progression-free survival favored the ctDNA-guided group (hazard ratio = 0.51, P = .014).
The ctDNA-guided strategy also enabled earlier detection of relapse. Median time to clinical recurrence was 9.5 months in the ctDNA-guided arm vs 13.4 months in the standard surveillance arm, corresponding to a median lead time of 3.9 months (P < .001). Among patients whose recurrence was confined to the liver and/or lungs, curative-intent treatment was performed in 42.3% of patients in the ctDNA-guided group vs 18.2% in the control group (P = .002). These patients also presented with more favorable metastatic characteristics, including three or fewer liver lesions (75.0% vs 28.6%, P = .005), tumors measuring 3 cm or smaller (90.0% vs 57.1%, P = .033), and unilobar disease (80.0% vs 28.6%, P = .002).
The authors concluded: “ctDNA methylation-guided dynamic surveillance improves the rate of curative-intent therapy for recurrence in patients with initially nonmetastatic [colorectal cancer] through earlier detection of resectable metastases, pending validation of long-term survival benefit in future analyses with mature data.”
Junjie Peng, MD, of the Department of Colorectal Surgery, Fudan University Shanghai Cancer Center and the Department of Oncology, Shanghai Medical College, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by the National Natural Science Foundation of China, the Science and Technology Commission of Shanghai Municipality, and the National Science and Technology Major Project. For full disclosures of the study authors, visit ascopubs.org.
