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

Table 1 Summary of key methodological concerns and recommended improvements

Methodological issue	Concern in Qi and Wu’s study[8]	Recommended approach
Selection bias	Only patients completing 6 cycles with good compliance were included	Intention-to-treat analysis; sensitivity analyses including non-completers
Temporal ambiguity	Biomarkers measured 1-3 months postoperatively; recurrence at 1 year	Landmark analysis; trajectory modeling; joint longitudinal-survival models
Confounding	Unadjusted comparisons; key covariates not measured or controlled	Multivariable Cox models; penalized regression; propensity score adjustment
Survival analysis	RFS reported as mean without censoring; no KM curves or Cox models	KM curves, log-rank tests, Cox regression; hazard ratios with CIs
Multiple testing	Multiple comparisons without correction; no primary endpoint	Prespecified primary endpoint; Bonferroni/FDR correction
Predictive performance	No AUC, calibration, or incremental value assessment	ROC/AUC; calibration plots; decision curve analysis; TRIPOD adherence
Molecular context	No molecular subtyping; Lewis antigen status not assessed	Incorporate MSI, HER2, EBV status; assess Lewis antigen phenotype

RFS: Recurrence-free survival; KM: Kaplan-Meier; CI: Confidence interval; AUC: Area under the curve; ROC: Receiver operating characteristic; FDR: False discovery rate; MSI: Microsatellite instability; HER2: Human epidermal growth factor receptor 2; EBV: Epstein-Barr virus.