Significance of Serum Tumor Markers in Esophageal and Gastric Cancers: A Systematic Literature Review.

[AIM] Serum tumor markers are helpful for diagnosis, monitoring treatment outcomes, and prognosis. However, their clinical utility for esophageal squamous cell carcinoma (ESCC) and gastric cancer (GC) remains unclear. This study aimed to comprehensively evaluate recent studies on serum tumor markers in ESCC and GC.

[METHODS] We conducted a systematic review and meta-analysis of studies published between January 2010 and March 2025 using PubMed. Overall, 84 and 468 articles on ESCC and GC were extracted, respectively. The sensitivity, specificity, positive predictive value, and summary receiver operating characteristic curves were calculated and evaluated using a systematic review and meta-analysis. Prognostic values were assessed using the hazard ratio based on univariate and multivariate analyses.

[RESULTS] In ESCC, squamous cell carcinoma antigen (SCC-Ag) exhibited the highest sensitivity (38.7%) and positive predictive value (85.2%); moreover, it was the only independent prognostic factor across multiple articles. Carcinoembryonic antigen (CEA) and cytokeratin 19 fragment had low sensitivity and predictive value, whereas serum p53 antibody demonstrated moderate prognostic relevance. In GC, CEA and CA125 had the highest sensitivity (37.2%) and positive predictive value (72.2%), respectively, and CA125 and CA72-4 were associated with peritoneal dissemination. CEA and CA125 levels were independent prognostic markers of GC.

[CONCLUSION] SCC-Ag is a key marker for ESCC diagnosis and prognosis. CEA and CA125 are valuable markers for GC prognosis, whereas CA125 and CA72-4 help detect peritoneal dissemination. Further research integrating the molecular characteristics of each tumor marker is warranted.