Comparative Analysis of Driver Mutations, Cancer Stage, and Metastatic Burden in Patients with Lung Adenocarcinoma with Prism Compared to COPD and Normal Lung Function

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Abstract Rationale: Preserved Ratio Impaired Spirometry (PRISm) is a condition defined by an FEV1 < 80% predicted and FEV1/FVC ratio ≥ 0.7. While specific driver mutations, such as EGFR and ALK1,2, are well-documented in lung adenocarcinoma patients with chronic obstructive pulmonary disease (COPD), the mutation profile in PRISm patients remains underexplored in current medical literature. This study aimed to investigate the distribution and clinical implications of driver mutations in lung adenocarcinoma patients across different lung function groups, including PRISm, COPD, and normal lung function. Methods: A retrospective analysis was conducted of 147 adenocarcinoma patients treated in the Mount Sinai Health System from January 2018 to May 2024. Patients were categorized by lung function (normal, COPD, PRISm). We compared the prevalence of driver mutations (ALK, BRAF, EGFR, HER2, MET, KRAS, NRAS, PIK3C, RET, ROS1, TP53), emphysema, PD-L1 levels, ECOG performance, cancer stage, and metastases in patients with normal lung function, PRISm and COPD. Statistical analyses used Kruskal-Wallis and Chi-Square tests, with significance at p < 0.05. Results: COPD patients had a significantly higher prevalence of emphysema (p = 0.0005) and lower ECOG scores, indicating poorer functional status compared to PRISm and normal groups (p = 0.015). Cancer stages III and IV were more common in PRISm and COPD groups than in the normal group (p = 0.023). PRISm patients had a significantly higher metastatic burden (p = 0.036). PD-L1 expression was not statistically significant across groups, and no significant differences were found for driver mutations between patients with normal lung function, PRISm and COPD. Discussion: The findings reveal distinct profiles for lung adenocarcinoma patients based on lung function. PRISm and COPD patients had higher metastatic burden and more advanced cancer stages than patients with normal lung function, suggesting a more aggressive disease course. Higher emphysema prevalence and lower ECOG scores in COPD demonstrate how COPD phenotype can affect functional status. Although driver mutations did not vary significantly between patients with normal lung function, PRISm and COPD, lung function stratification may be valuable in guiding treatment. Conclusion: PRISm and COPD adenocarcinoma patients have a more aggressive disease profile compared to those with normal lung function, marked by greater metastatic burden and advanced stage of lung cancer. Lung cancer screening should be therefore emphasized in PRISm patients who meet lung canceer screening eligibility. Increased emphysema prevalence in lung cancer and its effect on ECOG performance may effect patient outcomes.

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