Establishment of Age-Specific Reference Intervals for CA 19-9 and CEA: A Retrospective Analysis of the Saudi Population

Introduction: Accurate interpretation of serum marker measurements is essential in clinical laboratory practice. Carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA) are widely used biomarkers, yet their serum concentrations may be influenced by demographic and non-malignant factors. This study aimed to establish age- and gender-stratified reference intervals (RIs) for a Saudi population and quantify the impact of these local limits on diagnostic specificity and stewardship. Methods: We retrospectively analysed 1,567 adult laboratory results (aged 15–100) from nationwide diagnostic centres. This study followed the CLSI EP28-A3c guidelines for the indirect estimation of reference intervals. Statistical analysis included Kruskal–Wallis and Mann–Whitney U tests to quantify differences across demographic strata. Non-parametric 97.5th percentiles were calculated to define population-specific upper reference limits (URLs). Results: Both markers varied significantly by gender (CA 19-9: P = 0.013; CEA: P < 0.001) and age (CA 19-9: P = 0.018; CEA: P < 0.001). Using universal thresholds, the proportion of individuals classified as abnormal for CEA rose 8-fold in the >70 age group. CA 19-9 abnormalities exhibited a distinct peak of 11.5% in the 61–70 age cohort. Inter-marker correlation was weak (ρ = 0.118, P < 0.001), indicating independent demographic influences on each biomarker. Conclusion: Serum CA 19-9 and CEA concentrations vary with age and gender, leading to high rates of clinical misclassification in seniors and specific middle-aged cohorts. These findings highlight the necessity of age-stratified reference intervals to reduce the misclassification of benign elevations.