Comorbidities as independent predictors of mortality in lung cancer: A real-world multivariate analysis from a Latin American tertiary center with integrated molecular profiling.

e20093 Background: Lung cancer patients frequently present with multiple comorbidities that may significantly influence survival beyond tumor-related factors. However, the independent contribution of non-oncologic conditions to mortality remains underexplored, particularly in real-world Latin American populations. Methods: We conducted a retrospective study of adult patients with non–small cell lung cancer treated at a tertiary center (2016–2023). Clinical, tumor, and comorbidity data and causes of death were collected. All-cause mortality was the primary outcome. Multivariate logistic regression adjusted for age, sex, and tumor stage was performed. Results: A total of 496 patients were included (54.6% women; median age 69 years). At diagnosis, 15% were stage I, 6% stage II, 13.8% stage III, and 65.2% stage IV. PD-L1 expression was assessed using tumor proportion score (TPS) in 254 patients: 41.3% were TPS < 1%, 37.8% had TPS 1–49%, and 20.9% had TPS ≥50%. EGFR were assessed in 298 patients, identifying mutations in exon 19 deletions 17.8% (n = 53), L858R 12.8% (n = 38), exon 20 insertions 3.7% (n = 11), ALK rearrangements were assessed in 275 patients identifying positivity 12.0% (n = 33), reflecting a biologically characterized real-world cohort enriched for actionable alterations. The most frequent comorbidities were smoking history (55.6%), hypertension (46.8%), COPD (16.7%), and diabetes (16.3%); pulmonary embolism (PE) occurred in 10.1%. Overall mortality was 60.7% (n = 296). Cause of death was available in 161 patients, of whom 18.8% were non-oncologic and 81.2% cancer-related. Non-oncologic deaths were mainly due to pulmonary infections (pneumonia/COVID-19), often progressing to septic shock (32.0%), followed by cardiovascular disease (heart failure, 10.0%), thromboembolic events, and chronic kidney disease (7.5%). In bivariate analysis, mortality was higher in men (67.9%) and increased with stage (stage IV: 77.3% vs stages I–II, p < 0.001). COPD (70.4% vs 58.8%, p = 0.02), cerebrovascular disease (78.8% vs 59.4%, p = 0.03), and PE (71.4% vs 59.5%, p = 0.05) were associated with mortality. In multivariate analysis, advanced stage was the strongest predictor of death (stage III OR 4.29, 95% CI 1.73–10.10; stage IV OR 15.20, 95% CI 6.70–33.72). COPD (OR 2.13, 95% CI 1.10–4.11), cerebrovascular disease (OR 3.36, 95% CI 1.11–10.25), and PE (OR 1.55, 95% CI 1.05–3.47) remained independently associated with mortality after adjustment for age, sex, and stage. Conclusions: COPD, cerebrovascular disease, and pulmonary embolism remained independent predictors of all-cause mortality after adjustment for key clinical factors. These results support the implementation of integrated care pathways focused on early comorbidity identification and proactive management to improve survival in lung cancer patients.