Hidden advanced physiology in non-metastatic gastrointestinal cancer: Malnutrition/cachexia and in-patient failure-to-rescue.

11102 Background: Cancer stage is often used as a proxy for inpatient risk, yet physiologic reserve may better determine outcomes. It was hypothesized that among gastrointestinal (GI) cancer hospitalizations without coded metastasis, malnutrition/cachexia identifies a vulnerable subgroup with complication burden, ICU escalation, and post-complication mortality approaching that of metastatic disease. Methods: A survey-weighted analysis of the National Inpatient Sample (NIS), 2016–2023, was conducted. Adult hospitalizations with any GI malignancy (ICD-10-CM C15–C20, C22–C25) were included; encounters with palliative care coding (Z51.5) were excluded. Metastatic disease was defined by C77–C79. Vulnerability was defined as malnutrition/cachexia (E43, E44, E46, R64). Major complications included sepsis, bleeding/transfusion, venous thromboembolism, acute kidney injury (AKI), bowel injury/peritonitis, and respiratory failure. ICU escalation proxies included mechanical ventilation and/or shock. Outcomes were compared across three groups: non-metastatic/no vulnerability, non-metastatic/vulnerable, and metastatic. Failure-to-rescue was defined among non-metastatic surgical hospitalizations as death following ≥1 major complication. Results: The cohort included 748,734 weighted hospitalizations; 39.6% had coded metastasis. Among non-metastatic admissions, vulnerability prevalence increased from 15.6% in 2016 to 21.9% in 2023. In-hospital mortality in the non-metastatic/vulnerable group (4.14% [95% CI, 4.00–4.29]) approximated metastatic mortality (3.96%) and exceeded non-metastatic/no vulnerability mortality (1.86% [95% CI, 1.81–1.91]). Compared with non-metastatic/no vulnerability, vulnerable admissions demonstrated higher ICU escalation (7.75% [95% CI, 7.56–7.94] vs 3.54%), AKI (27.30% [95% CI, 26.98–27.62] vs 17.25%), and any major complication (59.31% [95% CI, 58.95–59.67] vs 42.93%). Resource utilization was higher in the vulnerable group (LOS 9.33 vs 5.49 days; cost $33,156 vs $22,879). Among non-metastatic admissions with complications, mortality was higher with vulnerability (6.46% [95% CI, 6.24–6.69] vs 3.88%). In the non-metastatic surgical subcohort, failure-to-rescue mortality was 5.90% (95% CI, 5.59–6.22) with vulnerability versus 2.65%. Conclusions: Among U.S. GI cancer hospitalizations without coded metastasis, malnutrition/cachexia identifies a high-risk inpatient phenotype with complication burden, ICU escalation, and post-complication mortality closely resembling metastatic disease. These findings suggest physiologic vulnerability, rather than stage alone, drives inpatient risk and failure-to-rescue, supporting targeted inpatient risk stratification and earlier supportive interventions.