Impact of COPD on prognosis of lung cancer: from a perspective on disease heterogeneity

Wei Wang,1,* Shuang Dou,1,* Wenyan Dong,2 Mengshuang Xie,1 Liwei Cui,1 Chunyan Zheng,1 Wei Xiao1 1Department of Pulmonary Medicine, Qilu Hospital, Shandong University, Jinan, People’s Republic of China; 2Department of Geriatric Medicine, The Second Hospital of Shandong University, Jinan, People’s Republic of China *These authors contributed equally to this work Background: COPD is an important comorbidity of lung cancer, but the impact of COPD on the outcomes of lung cancer remains uncertain. Because both COPD and lung cancer are heterogeneous diseases, we evaluated the link between COPD phenotypes and the prognosis of different histological subtypes of lung cancer.Methods: In this retrospective study, subjects with a newly and pathologically confirmed diagnosis of lung cancer were enrolled from patients preparing for lung cancer surgery. All participants underwent pulmonary function test (PFT). The diagnosis of COPD was based on GOLD criteria. Lung cancer subtypes and COPD phenotypes were categorized by WHO classification of lung tumors and computer quantitative analysis of PFT. The HRs were estimated by Cox regression analysis.Results: Among 2,222 lung cancer patients, 32.6% coexisted with COPD. After adjustment for age, sex, body mass index (BMI), smoking status, and therapy method, COPD was significantly associated with the decreased overall survival (OS) of lung cancer (HR 1.28, 95% CI 1.05–1.57). With the increased severity of COPD, the OS of lung cancer was gradually worsened (HR 1.23, 95% CI 1.08–1.39). But surgical treatment and high BMI were independent prognostic protective factors (HR 0.46, 95% CI 0.37–0.56; HR 0.96, 95% CI 0.94–0.99). Moreover, in terms of disease heterogeneity, emphysema-predominant phenotype of COPD was an independent prognostic risk factor for squamous carcinoma (HR 2.53, 95% CI 1.49–4.30). No significant relationship between COPD phenotype and lung cancer prognosis was observed among adenocarcinoma, small cell lung cancer, large cell lung cancer, and other subtype patients.Conclusion: These findings suggest that COPD, especially emphysema-predominant phenotype, is an independent prognostic risk factor for squamous carcinoma only. Keywords: lung cancer, COPD, prognosis, histology, disease heterogeneity