Utility of Circulating Tumor DNA Assessment in Characterizing Recurrence Sites after Optimal Resection for Metastatic Colorectal Cancer

Introduction: Plasma ctDNA is a promising biomarker for metastatic colorectal cancer (mCRC); however, its role in characterizing recurrence sites after mCRC resection remains poorly understood. This single-institution study investigated the timing of ctDNA detection and its levels in the context of recurrence at different sites following mCRC resection. Methods: Patients who underwent optimal resection of CRC metastases involving the peritoneum, distant lymph nodes, or liver, with serial postoperative tumor-informed ctDNA assessments (Signatera) were included. Recurrence sites, as defined by surveillance imaging or laparoscopy, were categorized as peritoneal-only and other distant sites (liver, lung, lymph nodes, or body wall). Results: Among the 31 included patients, ctDNA was detected in all 26 (83.4%) patients with postoperative recurrence and was persistently undetectable in five patients who did not experience recurrence. At three months post-surgery, ctDNA was detected in 2/8 (25.0%) patients with peritoneal-only recurrence and 17/18 (94.4%) patients with distant recurrence (p < 0.001). Beyond three months, ctDNA was detected in the remaining six patients with peritoneal-only disease and one patient with distant disease. ctDNA detection preceded the clinical diagnosis of recurrence by a median of nine weeks in both groups. At recurrence, peritoneal-only recurrent cases exhibited lower ctDNA levels (median 0.4 MTM/ml, IQR 0.1-0.8) compared to distant recurrence (median 5.5 MTM/ml, IQR 0.8-33.3, p = 0.004). Conclusion: Peritoneal-only recurrence was associated with delayed ctDNA detection and low levels of ctDNA after optimal resection for mCRC. ctDNA testing may effectively characterize recurrence sites and may help guide subsequent treatments specific to the disease sites involved.