Association of Skeletal Muscle Radiodensity and Skeletal Muscle Index with Immunotherapy Response in Metastatic Non-Small Cell Lung Cancer

Sarcopenia and reduced skeletal muscle radiodensity have been proposed as potential biomarkers influencing the outcomes of immunotherapy in cancer patients. This retrospective study aimed to evaluate the prognostic significance of skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD), assessed by means of computed tomography imaging at the L3 level, in 76 male patients with metastatic non-small cell lung cancer treated with PD-1/PD-L1 inhibitors. Patients were categorized into high and low SMI/SMD groups based on body mass index-adjusted cut-off values. Clinical outcomes included treatment response, overall survival, and immune-related adverse events. While no statistically significant differences in overall survival were observed between groups stratified by SMI or SMD, patients with higher SMD demonstrated a significantly greater disease control rate (56.22 ± 8.04 vs. 48.36 ± 10.34 HU; <i>p</i> = 0.031). Additionally, a statistically significant interaction was observed between PD-L1 expression and SMI (<i>p</i> = 0.027), indicating that muscle mass may influence the prognostic value of PD-L1. Neither SMI nor SMD were associated with immune-related adverse event incidence. Multivariate analysis identified PD-L1 expression ≥ 50% as the only independent predictor of longer overall survival (Hazard Ratio = 0.29; <i>p</i> = 0.001). In conclusion, while neither SMI nor SMD independently predicted overall survival, SMD was associated with treatment response. Notably, SMI modified the prognostic relevance of PD-L1 expression, suggesting a potential role for muscle mass in refining immunotherapy stratification.