Prognostic Significance of Postoperative and Post-Adjuvant Circulating Tumor DNA in Resected Colon Cancer: A Systematic Review and Meta-Analysis

Background: Circulating tumor DNA (ctDNA) is a promising biomarker for detecting minimal residual disease in colon cancer. We performed a systematic review and meta-analysis to assess the prognostic value of postoperative and post-adjuvant chemotherapy (ACT) ctDNA positivity in resected colon cancer. Methods: We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library for studies evaluating ctDNA after curative-intent surgery and/or ACT. Hazard ratios (HRs) for recurrence-free survival (RFS), disease-free survival (DFS), and overall survival (OS) were pooled using random-effects models. Results: Twenty-three studies comprising 10,217 patients were included. Postoperative ctDNA positivity was significantly associated with worse RFS (HR: 5.46, 95% CI: 3.79–7.85, p < 0.01, I² = 88%). In stage III disease, the pooled HR was 4.52 (95% CI: 2.90–7.05), while in stage II disease, the pooled HR was 6.67 (95% CI: 0.94–46.01). Post-ACT ctDNA positivity was associated with a marked increase in risk of recurrence (HR: 11.21, 95% CI: 6.92–18.15, p < 0.01, I² = 58%). Among stage III patients, the pooled HR was 10.83 (95% CI: 5.38–21.82), with sensitivity analysis yielding a stable estimate (HR: 6.84, 95% CI: 4.58–10.21, I² = 8%). Postoperative ctDNA positivity was also associated with inferior OS (HR: 3.99, 95% CI: 2.43–6.55, p < 0.01, I² = 90%) and worse DFS (HR: 4.92, 95% CI: 2.60–9.32, p < 0.01, I² = 83.5%). Conclusions: Postoperative and post-ACT ctDNA positivity are strong predictors of recurrence and mortality in resected colon cancer. ctDNA represents a robust biomarker of minimal residual disease that can inform risk-adapted treatment strategies. Prospective randomized trials are needed to determine whether ctDNA-guided management improves survival outcomes.