Prognostic Value of Treatment-Related Body Composition Changes in Metastatic NSCLC Receiving Nivolumab

<i>Background and Objectives:</i> This study aimed to evaluate the prognostic impact of baseline body composition measurements and changes in muscle and adipose tissue during treatment on overall survival (OS) in metastatic non-small cell lung cancer (NSCLC) patients treated with nivolumab. <i>Materials and Methods:</i> Eighty-eight metastatic NSCLC patients who were initiated on nivolumab between January 2022 and December 2024 were retrospectively analyzed. Body composition parameters were derived from baseline and 3-month ¹⁸F-FDG PET/CT scans at the L3 level, including psoas muscle index (PMI), skeletal muscle index (SMI), intramuscular adipose content (IMAC), and subcutaneous fat density (SFD). Treatment-related changes in body composition were evaluated, and survival analyses were performed using Kaplan-Meier estimates and Cox regression models. <i>Results:</i> Overall, 34.1% (<i>n</i> = 30) of patients were classified as sarcopenic. Median OS was significantly longer in non-sarcopenic patients (19 months vs. 5 months, <i>p</i> < 0.001). In univariate analysis, older age, higher comorbidity burden, liver metastasis, baseline sarcopenia, and adverse treatment-related changes in muscle and nutritional parameters were found to be associated with OS. In multivariate analysis, only unfavorable changes in skeletal muscle (ΔSMI; HR 3.39, <i>p</i> = 0.003) and subcutaneous fat radiodensity (ΔSFD; HR 2.45, <i>p</i> = 0.02) remained independent adverse prognostic factors. Baseline body composition parameters did not maintain their independence in multivariate models. <i>Conclusions:</i> Our study demonstrates that muscle loss or insufficient gain and unfavorable changes in subcutaneous fat radiodensity during nivolumab treatment more strongly predict overall survival compared to baseline measurements. These findings highlight the clinical importance of monitoring dynamic body composition throughout treatment, rather than static assessments, in NSCLC patients receiving immunotherapy.