Background/Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.

Background/Objectives: Neutrophil-to-lymphocyte ratio (NLR), a marker of systemic inflammation, has prognostic value in non-small cell lung cancer (NSCLC), but its longitudinal performance in routine care is unclear. We evaluated baseline and 12-month changes in NLR and hemoglobin in a single-center, Eastern European cohort. Methods: In this retrospective study, 180 adults with histologically confirmed NSCLC, diagnosed May 2022–April 2024 at a Romanian tertiary center, were followed until 30 April 2025. Baseline demographics, tumor characteristics, molecular profiles, laboratory parameters, and treatments were extracted from electronic health records. Progression-free survival (PFS) was the primary endpoint, overall survival (OS) the secondary, analyzed using Kaplan–Meier curves and Cox proportional hazards models. An additional treatment-start-anchored sensitivity analysis in treated patients was conducted. Results: The cohort (median age 67.8 years, 68.9% stage IV) received chemo-immunotherapy (58.9%), immunotherapy (26.7%), chemotherapy (9.4%), or supportive care (5.0%). Median for PFS was 8.2 months and for OS 14.5 months. A high baseline NLR (≥3, 58.9%) increased progression risk (HR 1.60, 95% CI 1.10–2.32, p = 0.014), with a trend for worse OS (HR 1.45, 95% CI 0.99–2.12). A 12-month NLR increase (62.2%) further elevated progression risk (HR 1.52, 95% CI 1.05–2.20, p = 0.026). Low hemoglobin (<12 g/dL) had a non-significant effect (HR 1.38, 95% CI 0.97–1.96, p = 0.074). PD-L1 ≥ 50% and chemo-immunotherapy correlated with longer PFS. Findings were consistent in the treatment-start anchored sensitivity analysis. Conclusions: These exploratory findings suggest that inexpensive hematologic markers can complement clinical assessment in advanced-stage NSCLC; prospective multi-center validation is warranted.

Background and Objectives: In real-world NSCLC management, prognostic assessment extends beyond tumour staging and molecular profiling, which represent a partial timeframe of disease biology. Routinely collected inflammatory and haematological markers may better reflect the dynamic host–tumour interactions during treatment. This study assessed the prognostic significance of baseline and longitudinal neutrophil-to-lymphocyte ratio (NLR) and haemoglobin levels on survival outcomes in a real-world NSCLC cohort. Materials and Methods: We conducted a retrospective observational cohort study of 615 patients with histologically confirmed NSCLC diagnosed between 1 May 2022 and 30 April 2024 at a tertiary referral centre in western Romania. Survival outcomes, including progression-free and overall survival, were analysed through Kaplan–Meier curves, complemented by 12-month restricted mean survival time estimates. High NLR was defined as ≥3 and low haemoglobin as <12 g/dL. Longitudinal changes were evaluated at 6 and 12 months, with 12-month analyses restricted to patients alive at that landmark. Results: The cohort had a median age of 66 years (IQR 60–72) and was predominantly male (66.3%). Most patients presented with advanced disease (60.3% stage IV, 23.6% stage III). At baseline, 57.1% (n = 351) exhibited high NLR and 39.8% (n = 245) had low haemoglobin. Median PFS was 9.0 months (IQR 4.5–15.5), and median OS was 16.5 months (IQR 8.5–27.0). Stage IV disease was associated with shorter PFS than stages I–II (7.0 vs. 20.8 months; log-rank p < 0.001). High-baseline NLR showed a borderline association with shorter PFS (adjusted HR 1.40; 95% CI 0.98–1.95). Among the 436 patients alive at 12 months, NLR increased in 56.7% of cases, and this increase showed a non-significant trend toward shorter PFS (HR 1.35; 95% CI 0.95–1.90; p = 0.09) in a 12-month landmark analysis. Conclusions: Baseline systemic inflammation and anaemia are highly prevalent in real-world NSCLC patients and cluster with advanced disease. Elevated NLR was associated with poorer survival outcomes, whereas low haemoglobin did not demonstrate a significant independent association in adjusted analyses. These haematological parameters are accessible tools for prognostic assessment in routine clinical practice.