The Impact of Body Composition on Outcomes in NSCLC Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review.

Immune checkpoint inhibitors targeting the PD-1/PD-L1 axis have become a standard in the treatment of all stages of non-small lung cancer. Beyond tumor-intrinsic biomarkers like PD-L1 expression, evidence points to the role of patient-related factors, such as body mass index, sarcopenia, and cachexia. These body composition parameters may reflect metabolic reserve or even immune competence and could help stratify outcomes in patients treated with PD-1 and PD-L1. This systematic review aims to evaluate the impact of body composition-specifically BMI, pretreatment weight loss, sarcopenia, and cachexia-on clinical outcomes such as progression-free and overall survival in NSCLC patients treated with immune checkpoint inhibitors. A systematic literature search was conducted across multiple databases including PubMed, Google Scholar, and Science Direct. We included full-text original research articles (1 January 2020-1 May 2025) reporting clinical outcomes of NSCLC patients treated with PD-1 or PD-L1 inhibitors, in relation to body composition factors (BMI, pretreatment weight loss, sarcopenia, cachexia). Eligible studies involved adults (>18 years) and included observational cohorts or controlled trials; animal or in vitro studies were excluded. Data extraction and risk of bias assessments were performed independently by two reviewers, with discrepancies being resolved through a third one. From 12,358 records identified, 21 studies met the inclusion criteria. Most were retrospective cohorts assessing the impact of pre-treatment weight loss, cachexia, and sarcopenia on ICI outcomes in NSCLC. These factors consistently predicted poorer survival and response, while BMI alone showed limited prognostic value. Considerable heterogeneity in body composition definitions and outcome reporting was observed. Body composition-particularly weight loss, cachexia, and sarcopenia-significantly impacts survival and response in NSCLC patients treated with ICIs. These factors reflect immune-metabolic dysfunction that may impair treatment efficacy. BMI alone is insufficient; routine assessment of muscle mass and cachexia could improve risk stratification.