Prognostic Value of Circulating Tumor DNA for Recurrence Risk in Stage III Colorectal Cancer: A Systematic Review and Meta-Analysis

Abstract

Background: Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for minimal residual disease (MRD) detection and recurrence risk stratification in colorectal cancer (CRC). However, its prognostic significance in stage III CRC remains incompletely defined. This meta-analysis aimed to evaluate the association between postoperative ctDNA positivity and recurrence risk in patients with stage III CRC. Methods: PubMed, Embase, and the Cochrane Library were searched for potentially eligible studies published up to April 2025. Pooled risk ratio (RR) and pooled hazard ratio (HR) were calculated to evaluate recurrence rate and the prognosis of recurrence-free survival (RFS) following CRC surgery and ACT. Meta-analysis was performed using a random-effects model. Results: A total of ten studies involving 2461 stage III CRC patients were included. Postoperative ctDNA positivity was significantly associated with an increased risk of recurrence (RR = 4.39, 95% CI, 3.45-5.58, P < .00001) and a poorer RFS (HR = 6.56, 95% CI, 4.80-8.98, P < .00001). The pooled analysis showed that ctDNA-positive patients had a significantly higher risk of recurrence following ACT (RR = 4.80, 95% CI, 3.17-7.26, P < .00001) and a worse RFS (HR = 10.00, 95% CI, 4.84-20.66, P < .00001). Conclusion: Postoperative ctDNA positivity is a strong prognostic marker of recurrence in patients with stage III CRC and could guide individualized surveillance and adjuvant therapy decisions. Further prospective studies are warranted to validate its routine clinical use. © 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.