Association Between Severe Vitamin D Deficiency and 5-Year Healthcare Utilization and Mortality in Patients with Non–Small Cell Lung Cancer: A Cohort Study

Background and Objectives: Non-small cell lung cancer (NSCLC) is a common malignancy and a leading cause of cancer-related mortality worldwide. Vitamin D supplementation may improve survival in patients with early stage NSCLC and low serum 25-hydroxyvitamin D [25(OH)D] levels. Using real-world data from the TriNetX research platform, this study aimed to examine the associations between baseline serum 25-hydroxyvitamin D [25(OH)D] concentrations and the risks of all-cause mortality, first hospitalization, first emergency department (ED) visit, and first intensive care unit (ICU) admission among adults with NSCLC. Materials and Methods: A retrospective cohort study using the TriNetX database was conducted to investigate the relationship between vitamin D deficiency and patients with non-small cell lung cancer (NSCLC) in adults (≥20 years). Patients were stratified into four groups according to serum 25-hydroxyvitamin D [25(OH)D] levels: Group A (≤10 ng/mL; severe vitamin D deficiency), Group B (>10 to 20 ng/mL), Group C (>20 to 30 ng/mL), and Group D (>30 to 100 ng/mL; normal vitamin D status). To minimize exposure misclassification, all patients required a confirmatory serum 25(OH)D measurement within 3 months before the index date. After 1:1 propensity score matching, patients were followed for up to 5 years to assess the predefined clinical outcomes. Results: A total of 4794 eligible patients with NSCLC were included and stratified into four groups: Group A (n = 738; 15.4%), Group B (n = 1204; 25.1%), Group C (n = 1237; 25.8%), and Group D (n = 1615; 33.7%). After propensity score matching, baseline characteristics were generally well balanced across the vitamin D groups, with only minor residual imbalances in eGFR and serum albumin. After propensity score matching, patients with severe vitamin D deficiency (Group A) consistently had a higher risk of all-cause mortality at 1, 3, and 5 years than those in Groups B, C, or D (all p < 0.05). Group A also showed higher risks of 1-year first ED visits, malnutrition, and bone metastasis in selected comparisons, and higher risks of first ED visits throughout follow-up when compared with Group D. Conclusions: In this real-world analysis of patients with NSCLC, severe vitamin D deficiency at baseline was consistently associated with higher all-cause mortality than all other baseline vitamin D categories over 5 years. Associations with first hospitalization, ED visit, and ICU admission were less consistent and were most evident in comparison with study-defined normal vitamin D status, particularly for first ED visit. However, low serum 25(OH)D levels may primarily reflect overall clinical vulnerability, and their independent prognostic value remains uncertain.