Circulating tumor DNA as a biomarker for progression and survival in esophageal cancer after neoadjuvant therapy and esophagectomy: a systematic review and meta-analysis

Background: Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for monitoring treatment response and predicting outcomes in cancer. This meta-analysis aimed to evaluate the prognostic value of ctDNA in predicting survival outcomes and pathologic complete response (pCR) in esophageal cancer (EC) patients undergoing neoadjuvant therapy (NAT). Methods: A systematic search of PubMed, Web of Science, and Embase was conducted between August and September 2024. Observational studies and randomized clinical trials were included if they reported associations between ctDNA detection and progression-free survival (PFS), overall survival (OS), or pCR. Fixed-effects models were used to pool hazard ratios (HRs) and odds ratios (ORs). Heterogeneity was quantified using I 2 statistics, and publication bias was assessed via funnel plots and Egger’s test. Results: Among 71 studies screened, 10 met the inclusion criteria (n = 334 patients). Baseline ctDNA detection was not significantly associated with PFS, OS, or pCR (P > 0.05). However, ctDNA detection post-NAT was significantly associated with worse PFS (HR 3.81; 95% CI: 2.19–6.64), OS (HR 3.00; 95% CI: 1.64–5.50), and lower odds of pCR (OR 0.26; 95% CI: 0.09–0.73). Similarly, ctDNA detection post-surgery predicted worse PFS (HR 4.17; 95% CI: 2.17–8.04) and OS (HR 4.00; 95% CI: 1.90–8.42). Conclusion: ctDNA detection following NAT and surgery is a strong predictor of poor survival outcomes and lower pCR rates in EC. These findings underscore ctDNA’s potential as a biomarker for risk stratification and personalized treatment planning in EC patients. Further standardization of ctDNA detection methods is essential to optimize its clinical utility.