Cancer cachexia and wasting phenotypes in relation to inpatient severity, infection, resource utilization, and mortality in U.S. cancer hospitalizations: National Inpatient Sample, 2018–2022.

Abstract

e23199 Background: The obesity paradox in cancer is often defined using body mass index, which may poorly reflect metabolic vulnerability. Cachexia, malnutrition, and sarcopenia are wasting phenotypes that may better explain inpatient risk. National data comparing these phenotypes with obesity alone during cancer hospitalizations is limited. Methods: A serial cross-sectional, hospitalization-level analysis of the 2018–2022 Healthcare Cost and Utilization Project National Inpatient Sample (NIS) was conducted using discharge-level survey weights with hospital clustering and stratification. Adult hospitalizations with a principal diagnosis of malignancy were identified using ICD-10-CM codes C00–C97 and D45–D47. Nutritional phenotypes were defined using inpatient diagnosis proxies for cachexia, malnutrition, sarcopenia, and obesity, and categorized as neither wasting nor obesity, wasting phenotype, obesity alone, or wasting with obesity. Outcomes included All Patient Refined Diagnosis Related Group (APR-DRG) severity, extreme inpatient severity (APR-DRG level 4), in-hospital mortality, infection using a sepsis proxy, length of stay (LOS), and total hospitalization cost. Survey-weighted multivariable models adjusted for demographics, payer, socioeconomic status, admission characteristics, cancer type, and hospital characteristics. Results: Among 961,655 unweighted cancer hospitalizations representing 4,808,274 nationally, wasting phenotypes were associated with higher inpatient vulnerability. Mean APR-DRG severity was highest among hospitalizations with wasting plus obesity (3.44) and wasting alone (3.40), compared with obesity alone (2.55) and neither wasting nor obesity (2.37). Extreme severity occurred disproportionately among wasting phenotypes, with adjusted odds ratios of 4.90 (95% CI 4.70-5.10) for wasting alone and 6.30 (95% CI 5.63-7.04) for wasting with obesity. LOS and cost were highest among wasting phenotypes, particularly wasting with obesity (LOS 14.25 days; cost $44,246). In-hospital mortality and sepsis followed similar gradients, with markedly increased adjusted odds for wasting phenotypes and lower mortality among obesity alone (OR 0.80, 95% CI 0.76–0.84). Conclusions: When evaluated using inpatient wasting phenotypes, the apparent obesity paradox in cancer is largely explained by the presence or absence of cachexia, malnutrition, and sarcopenia. These phenotypes are dominant drivers of inpatient severity. Incorporating wasting phenotypes into inpatient risk stratification may improve identification of high-risk oncology admissions.