Abstract
The primary aim of lung cancer screening is to improve survival from lung cancer by identifying early stage non-small cell lung cancers and prolong survival through their surgical removal. In a post-hoc analysis of 10,054 screening participants from the National Lung Screening Trial (NLST) we show that the risk of lung cancer, according to the PLCOm2012 model, is closely related to the likelihood of having chronic obstructive pulmonary disease (COPD). Those at greatest risk for lung cancer have the highest prevalence of COPD and greater likelihood of dying of a non-lung cancer cause. This "competing cause of death" effect occurs because smokers eligible for lung cancer screening have a high prevalence of comorbid disease and greater likelihood of dying from cardiovascular disease, respiratory disease or other cancers. This means high risk smokers at greatest risk of lung cancer may not necessarily benefit from screening due to greater inoperability and premature death. In this analysis we show that the benefit of annual computed tomography (CT) screening is greatest in those with normal lung function or only mild-to-moderate COPD. We found no mortality benefit in those with severe or very severe COPD (GOLD 3-4). We also show that the efficiency of screening, based on optimizing the number of lung cancer deaths averted per 1,000 persons screened, is best achieved by screening those at intermediate risk. By combining clinical risk variables with a gene-based risk score, even greater reductions in lung cancer mortality can be achieved with CT. We suggest a biomarker-led outcomes-based approach may help to better define which eligible smokers might defer screening (low risk of lung cancer), discontinue screening (high risk of overtreatment with little benefit) or continue screening to achieve the greatest reduction in lung cancer mortality.