Crit Rev Oncol Hematol. 2026 Oct 17. pii: S1040-8428(26)00539-1. [Epub ahead of print]228
105652
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.
Keywords: CtDNA; Esophageal cancer; Gastric cancer; Meta-analysis; Prognosis