Lung Cancer in Chronic Obstructive Pulmonary Disease Patients, It Is Not Just the Cigarette Smoke

Pablo Sanchez-Salcedo; Javier J. Zulueta


Curr Opin Pulm Med. 2016;22(4):344-349. 

In This Article

Airflow Obstruction and Lung Cancer

The first epidemiological studies associating these two entities go back to almost 30 years ago, when Skillrud et al.[17] and Tockman et al.[18] described a four-fold increase in lung cancer incidence and mortality, respectively, in patients with airflow obstruction. Several studies have later confirmed this observation, with a two to four-fold increase in lung cancer risk among patients with COPD.[19–23] The degree of airflow obstruction has also been assessed, but the evidence has been contradictive. In the BMI, Airflow obstruction, Dyspnea, Exercise performance observational cohort of patients with COPD attending pulmonary clinics, de Torres et al.[24] described an increased lung cancer risk among patients with mild and moderate airflow obstruction [hazard ratio 3.05; 95% confidence interval (CI) 1.41–6.59, and hazard ratio 2.06; 95% CI 1.01–4.18, respectively]. In the Pamplona sub-cohort of the International Early Lung Cancer Detection Program, 94% of the lung cancer cases detected in patients with COPD occurred in individuals with mild or moderate COPD.[22] However, regression analysis failed to show a significant association. These results contrast to those from other cohorts where opposite results have been observed.[19,21,23,25] For instance, in the Pittsburgh Lung Screening Study,[21] and in the National Health and Nutrition Examination Survey,[25] the risk for incident lung cancer was significantly higher in patients with COPD with more severe degrees of airway obstruction.

In a recent meta-analysis, Wasswa-Kintu et al.[26] concluded there was a strong association between a reduced FEV1 and lung cancer. Compared with the highest quintile of FEV1 (>100% predicted), the lowest quintile of FEV1 (<~70% predicted) was associated with a two and almost four-fold increase in lung cancer risk in men and women, respectively. In patients with COPD, even a small reduction in FEV1% predicted (below 90%) showed an important lung cancer risk [odds ratio (OR) 2.56; 95% CI 1.29–5.07] after adjusting for covariates.[27]

Leaving risk assessment aside, some evidence has pointed out that lung cancer cases that develop in patients with COPD differ from those occurring in patients without airflow obstruction. In a recent study by Wauters et al.[28] involving DNA methylation profiling of 46 nonsmall cell lung carcinomas, the authors described a specific tumor microenvironment in patients with COPD characterized by a reduced immune cell infiltration. Even though there are other clinical variables that are likely to affect the methylation profile of the tumor, the effect of COPD was stronger than age, smoking behavior, emphysema, and others.[28] This could have important implications when considering treatment options in lung cancer patients with and without COPD.

Based on data from the subgroup of participants from the National Lung Screening Trial who had spirometry done (n = 18 714), Young et al.[29] described that the presence of COPD was associated with more aggressive lung cancers and significantly less or minimal overdiagnosis. The lung cancer prevalence was virtually the same and the overall distribution of lung cancer histology was comparable in patients with COPD who underwent screening by CT and chest radiograph, with no evidence of a histology shift.[29] On the other hand, 29 excess lung cancers were detected among individuals with normal lung function who underwent screening by CT, compared with the chest X-ray arm, all of them from the carcinoma in-situ subgroup, suggesting overdiagnosis in this subgroup.[29]