Rethinking carcinoembryonic antigen and carbohydrate antigen 19-9 in gastric cancer surveillance: From statistical association to clinical utility

Table 2 Emerging biomarker technologies for postoperative gastric cancer surveillance

Biomarker	Advantages	Limitations	Clinical readiness
CEA/CA19-9	Inexpensive, widely available, easily serialized	Low sensitivity/specificity; affected by non-malignant conditions	Established in guidelines but not validated as a standalone prognostic tool
Circulating tumor DNA (ctDNA)	Tumor-specific; detects MRD; identifies actionable mutations	Cost, assay standardization; CHIP interference; limited early-stage sensitivity	Investigational; multiple ongoing trials in GC
Circulating tumor cells	Captures metastatic phenotype; whole-cell analysis	Technical isolation challenges; low counts in early disease	Experimental; limited GC validation
Extracellular vesicles	Rich molecular cargo; immunomodulatory insights	Isolation variability; lack of standardized protocols	Pre-clinical/early translational
Methylated cfDNA	Epigenetic signal: High sensitivity in some assays	Assay complexity; limited prospective data	Investigational; promising early results
Multi-analyte panels (ctDNA + protein + fragmentomics)	Combines complementary signals; highest accuracy potential	Complexity; cost; validation needed	Active clinical trials; not yet guideline-endorsed

CEA: Carcinoembryonic antigen; CA19-9: Carbohydrate antigen 19-9; MRD: Minimal residual disease; CHIP: Clonal hematopoiesis of indeterminate potential; GC: Gastric cancer; cfDNA: Cell-free DNA.