Unpacking the Obesity Paradox in Lung Cancer: A Nationwide Analysis of In-Hospital Mortality From the US National Inpatient Sample (2020-2022).

Background Lung cancer remains the leading cause of cancer-related mortality worldwide. Although obesity is an established risk factor for multiple malignancies, numerous studies have reported an "obesity paradox," wherein patients with obesity demonstrate improved survival compared with normal-weight or underweight individuals. Whether this survival advantage reflects a true protective biological mechanism or methodological artifacts such as reverse causation driven by cancer cachexia and selection bias remains controversial, particularly within the acute inpatient setting. We evaluated the independent association between documented obesity and in-hospital mortality among lung cancer hospitalizations. Methods We performed a retrospective cross-sectional analysis of the US National Inpatient Sample (2020-2022). Adult hospitalizations (age ≥18 years) with a diagnosis of lung cancer were identified and dichotomized by the presence or absence of an International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) obesity code; the unit of analysis was the hospitalization rather than the individual patient, and the exposure was documented obesity coding rather than measured adiposity. Baseline demographics, comorbidities, and in-hospital complications were compared using the chi-squared test (categorical variables) and the Mann-Whitney U test (continuous variables). The primary outcome was in-hospital mortality; multivariable logistic regression adjusted for demographic, clinical, and hospital-level covariates. Results Of 61,963 unweighted lung cancer hospitalizations, 7,065 (11.4%) carried an obesity code. Obese patients were younger (median: 68 vs. 70 years) and more often female (4,090/7,065 (57.9%) vs. 28,011/54,898 (51%)). They had a higher prevalence of hypertension, diabetes, dyslipidemia, and obstructive sleep apnea (1,703 (24.1%) vs. 2,910 (5.3%)) but a lower weighted Elixhauser score (median: 10 vs. 16). In-hospital mortality was lower in the obese group (278 (3.9%) vs. 3,746 (6.8%); p<0.001). After adjustment, an obesity code was independently associated with 33% lower odds of in-hospital death (adjusted odds ratio (aOR): 0.67; 95% CI: 0.58-0.77; p<0.001). Conclusions Documented obesity coding was independently associated with lower in-hospital mortality among lung cancer hospitalizations. However, the low sensitivity of administrative obesity coding, a binary exposure that cannot separate normal-weight from cachectic patients, and the susceptibility of hospitalized cohorts to collider and reverse-causation bias mean this association should not be interpreted as a protective effect of adiposity. The paradox is most parsimoniously explained by confounding by illness severity rather than a therapeutic target, and the finding should be interpreted as an association involving documented obesity coding rather than an effect of adiposity itself.