Monthly Biological Variation of Five Lung Cancer Markers in Healthy Older Individuals: Evidence from Combined Prospective Cohort and Real-World Data Analyses

Background: Elderly populations face disproportionate lung cancer burdens; however, biological variation (BV) data for key tumor markers (carcinoma embryonic antigen [CEA], neuron-specific enolase [NSE], cytokeratin 19 fragment [Cyfra21-1], progastrin-releasing peptide [ProGRP], and squamous cell carcinoma antigen [SCC-Ag]) in this demographic remain scarce, impeding personalized result interpretation. This study explored BV for these five lung cancer markers among older Chinese individuals. Methods: ]) were estimated using nested ANOVA and Bayesian hierarchical modeling. Real-world data (N=8,003) were analyzed for CEA. Methods followed BV data critical appraisal checklist standards. Results: -derived reference change values (RCVs). Conclusions: This study establishes the first comprehensive BV database for lung cancer biomarkers in elderly Asians. Stable monthly variation enables flexible monitoring protocols. Our findings support implementing personalized RCVs for clinical interpretation and facilitate earlier therapeutic interventions for aging individuals.