Circulating Tumor DNA as a Biomarker for Recurrence After Curative Resection of Colorectal Cancer Liver Metastases: A Systematic Review and Meta-Analysis.

Colorectal liver metastases (CRLM) remain a leading cause of cancer-related mortality, with recurrence rates of 50 to 70% following curative-intent hepatic resection. Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for minimal residual disease (MRD) detection, yet its prognostic value in resected CRLM has not been systematically quantified. A systematic review and meta-analysis was conducted following PRISMA 2020 guidelines (PROSPERO: CRD420251177140). MEDLINE, Embase, Web of Science, Cochrane CENTRAL, and Scopus were searched through October 2025. Studies evaluating ctDNA as a prognostic biomarker in adults with resected CRLM were included. Hazard ratios (HRs) for recurrence-free survival (RFS) and overall survival (OS) were pooled using random-effects models. Evidence certainty was assessed using GRADE methodology. Ten studies (1034 patients) were included. Postoperative ctDNA positivity was significantly associated with inferior RFS in the MRD window (HR 3.28, 995% CI, 2.58-4.17; I² = 10%) and after adjuvant chemotherapy (HR 8.69, 995% CI, 5.43-13.90; I² = 0%). ctDNA positivity was also associated with reduced OS (HR 7.11, 995% CI, 3.87-13.09). ctDNA detection preceded radiological recurrence by 3.5 to 6.1 months. Preoperative ctDNA was not a statistically significant predictor. ctDNA is a promising prognostic biomarker in resected CRLM, strongly associated with recurrence and mortality. However, prospective randomized trials are needed before routine clinical implementation.