Multicenter phase 3 trial of dynamic ctDNA methylation monitoring guiding postoperative surveillance in nonmetastatic colorectal cancer

The multicenter prospective phase 3 FIND trial in China investigated whether 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. Patients were randomized to ctDNA-guided surveillance (n=289) or standard computed tomography (CT)-based monitoring (control group; n=295). 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 endpoint was the proportion of patients with recurrence receiving curative-intent metastasis-directed therapy. With a median follow-up of 23.3 months, recurrence rates were similar between the groups (18.0% versus 18.6%; p=0.919). The ctDNA-guided group had a significantly higher rate of curative-intent treatment (48.1% versus 23.6%; relative risk 2.03; p=0.008). The median time to clinical recurrence was significantly shorter in the ctDNA-guided group than in the control group (9.5 versus 13.4 months; p<0.001). Among recurrences confined to the liver and/or lungs, the ctDNA-guided group showed higher curative resection rates (42.3% versus 18.2%; p=0.002). These patients had more favorable hepatic metastatic features: fewer lesions, smaller tumor size, and more unilobar disease. The authors conclude that 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.