Prognostic value of circulating tumor DNA in esophageal and gastric cancer by treatment stage: a systematic review and meta-analysis.

BACKGROUND

The prognostic value of circulating tumor DNA (ctDNA) remains controversial. This meta-analysis systematically evaluates the association between ctDNA status and prognosis in esophageal cancer (EC) and gastric cancer (GC) (including gastroesophageal junction cancer), stratified by resectability and treatment stage.

METHODS

PubMed, Web of Science, EMBASE and Scopus were systematically searched up to February 2026. Pooled hazard ratios (HRs) and 95% confidence intervals (95%CIs) were used to quantify disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS).

RESULTS

Forty-four studies were included: 28 on resectable cancer, 17 on unresectable cancer (among which one study covered both types). In resectable cancer, ctDNA positivity was associated with worse DFS at baseline (HR=2.45, 95%CI: 1.18-5.07), after neoadjuvant therapy (HR=3.89, 95%CI: 2.50-6.06), after radical surgery (HR=6.76, 95%CI: 4.72-9.67), and follow-up (HR=19.17, 95%CI: 12.69-28.96). ctDNA positivity was also associated with worse OS at baseline (HR=1.89, 95%CI: 1.13-3.16), after neoadjuvant therapy (HR=3.40, 95%CI: 2.03-5.69), and after radical surgery (HR=4.52, 95%CI: 2.70-7.58). In resectable cancer, ctDNA positivity was associated with both DFS and OS, and the association differed between treatment time points (DFS: Q-test P<0.001; OS: Q-test P=0.05). In unresectable cancer, baseline ctDNA positivity was associated with worse PFS (HR=2.17, 95%CI: 1.31-3.60) and OS (HR=2.04, 95%CI: 1.54-2.70). During treatment, ctDNA positivity was associated with worse PFS (HR=2.72, 95%CI: 1.63-4.52) and OS (HR=2.63, 95%CI: 1.52-4.55).

CONCLUSION

ctDNA positivity was associated with worse prognosis in both resectable and unresectable EC and GC. In resectable cancer, the association with DFS and OS differed between treatment time points.