Visceral Adipose Tissue Radiodensity as a Potential Biomarker of Immunotherapy Efficacy in Metastatic Non-Small Cell Lung Cancer Patients

Introduction. Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality worldwide. Immunotherapy with immune checkpoint inhibitors (ICIs) has improved clinical outcomes, yet predictive biomarkers of treatment efficacy are limited. Recent attention has turned to body composition, particularly adipose tissue characteristics, as potential prognostic indicators. While subcutaneous adipose tissue (SAT) has shown promise, the role of visceral adipose tissue (VAT) radiodensity remains unclear. This study aimed to assess the prognostic significance of VAT radiodensity as a potential biomarker of ICI efficacy in patients with metastatic NSCLC. Methods. A retrospective cohort study was conducted on 92 patients with metastatic NSCLC treated with ICIs. VAT radiodensity was measured using contrast-enhanced CT scans at the L3 vertebral level. Radiodensity was defined as the mean Hounsfield unit (HU) value within a 1 cm2 area of VAT. VAT radiodensity was analyzed as both a categorical and a continuous variable. Quartile ranges were as follows: Q1 (-150HU to -100HU), Q2 (-99HU to -91HU), Q3 (-90HU to -73HU), Q4 (-72HU to -50HU). Survival data were analyzed using Kaplan-Meier curves and Cox proportional hazards models adjusted for relevant clinicopathological covariates. A significance threshold of p < 0.05 was applied. Results. The median overall survival was 15.9, 21.9, 20.1, and 14.2 months for quartiles Q1, Q2, Q3, and Q4, respectively (log-rank p = 0.6331). Multivariable Cox models showed no significant association between VAT radiodensity and NSCLC-specific mortality in categorical or continuous analyses (p > 0.05 across all models). However, PD-L1 expression ≥ 50% emerged as a strong independent predictor of reduced mortality risk (HR = 0.34; p < 0.001). A significant interaction between VAT radiodensity and PD-L1 status was observed (p < 0.001), suggesting possible modulation of immunotherapy response by metabolic factors. Restricted cubic spline analysis showed the non-linear association between mortality risk and VAT radiodensity in patients with metastatic NSCLC. Conclusions. VAT radiodensity was not an independent predictor of survival in metastatic NSCLC patients treated with ICIs. Nevertheless, its interaction with PD-L1 expression highlights a potential modifying role that warrants further exploration. These findings support the integration of VAT radiodensity into multivariable prognostic models rather than as a standalone biomarker.