Circulating tumor DNA as a predictive biomarker for colorectal cancer postsurgical recurrence: a systematic review and meta-analysis

Abstract Purpose Colorectal carcinoma constitutes a predominant etiology of oncological mortality globally. This systematic review and meta-analysis elucidated the prognostic utility of circulating tumor DNA (ctDNA) as a predictive biomarker for postsurgical recurrence in colorectal cancer patients. Methods Two independent investigators conducted systematic literature search across PubMed, Web of Science, Embase, Scopus, and clinical trial registries. Studies investigating ctDNA prognostic significance for colorectal cancer recurrence were incorporated. Random-effects models were implemented utilizing restricted maximum likelihood methodology. The study quality was assessed using Newcastle–Ottawa Scale. Results Following screening of 2259 records, 11 studies were incorporated. ctDNA-positive patients exhibited significantly elevated recurrence risk as compared to ctDNA-negative counterparts (pooled HR: 2.34; 95% CI: 1.90–2.79; p < 0.001). Moderate heterogeneity was observed ( I 2 = 66.40%), attributable to patient stage distribution, sampling timing, detection platforms, and mutational panel variations. Stage I-III patients demonstrated exceptional consistency (HR: 2.04, I 2 = 0.00%). Detection platforms showed robust performance: droplet digital PCR (HR: 3.63), next-generation sequencing (HR: 2.67), and Safe-SeqS (HR: 2.16), with no significant differences ( p = 0.10). Adjuvant chemotherapy analysis revealed differential performance: treated patients (HR: 2.50; 95% CI: 2.08–2.93) versus untreated (HR: 1.70; 95% CI: 1.07–2.34; p = 0.04). Extended analysis confirmed prognostic utility for overall survival (HR: 2.24) and surveillance recurrence-free survival (HR: 3.54). Conclusions ctDNA represents a robust prognostic biomarker for postsurgical colorectal cancer recurrence with consistent cross-platform performance. Enhanced prognostic value in adjuvant chemotherapy patients supports personalized surveillance implementation, though methodological standardization remains warranted.

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