Comorbidity, malnutrition, and their additive effect on prognosis in cancer patients: a multicenter cohort study

BACKGROUND: With population aging and the rising prevalence of chronic disease worldwide, comorbidity is prevalent among patients with cancer. However, the relationship between comorbidity and malnutrition, as well as their combined impact on prognosis remains poorly understood. METHODS: We analyzed data of 12,947 cancer patients from a large-scale multicenter cohort study. Comorbidity burden was quantified using the modified age-adjusted Charlson Comorbidity Index (mACCI). Malnutrition was diagnosed using the Global Leadership Initiative on Malnutrition (GLIM). Clinical outcomes included overall survival, 30-day mortality, prolonged length of hospital stay (LOS), and increased hospitalization costs. Multivariable regression models were employed. RESULTS: 10,673 (82.4%) patients were diagnosed with malnutrition, and 7,982 (62.0%) patients had a high comorbidity burden (mACCI ≥ 2). The comorbidity burden and malnutrition were significantly correlated only in patients with stage I disease (OR = 1.60, 95% CI: 1.13-2.25). Some comorbidities, including anemia, non-stroke cardiovascular/cerebrovascular disease, chronic kidney disease, chronic pulmonary disease, and diabetes, had specific associations with the phenotypic or etiological characteristics of malnutrition (all p < 0.05). Malnutrition was an independent prognostic factor for all four adverse outcomes (all p < 0.05), and high comorbidity burden was an independent prognostic factor for prolonged LOS and increased costs (all p < 0.05). Patients with both high comorbidity burden and malnutrition exhibited a higher risk of 30-day mortality (OR = 4.58, 95% CI: 1.30-29.1), prolonged LOS (OR = 1.33, 95% CI: 1.12-1.58), and increased costs (OR = 1.35, 95% CI: 1.14-1.60) compared with those with low comorbidity burden and well-nourished status. CONCLUSION: The relationship between comorbidity burden and malnutrition was stage-dependent, and their coexistence had an additive effect on the prognosis of cancer patients. These findings highlight the importance of integrating comorbidity assessment into the nutritional management of cancer patients, particularly in early-stage disease.