Abstract
Lung cancer risks at which individuals should be screened with computed tomography (CT) for lung cancer are undecided. This study's objectives are to identify a risk threshold for selecting individuals for screening, to compare its efficiency with the U.S. Preventive Services Task Force (USPSTF) criteria for identifying screenees, and to determine whether never-smokers should be screened. Lung cancer risks are compared between smokers aged 55-64 and ≥ 65-80 y. Applying the PLCO(m2012) model, a model based on 6-y lung cancer incidence, we identified the risk threshold above which National Lung Screening Trial (NLST, n = 53,452) CT arm lung cancer mortality rates were consistently lower than rates in the chest X-ray (CXR) arm. We evaluated the USPSTF and PLCO(m2012) risk criteria in intervention arm (CXR) smokers (n = 37,327) of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). The numbers of smokers selected for screening, and the sensitivities, specificities, and positive predictive values (PPVs) for identifying lung cancers were assessed. A modified model (PLCOall2014) evaluated risks in never-smokers. At PLCO(m2012) risk ≥ 0.0151, the 65th percentile of risk, the NLST CT arm mortality rates are consistently below the CXR arm's rates. The number needed to screen to prevent one lung cancer death in the 65th to 100th percentile risk group is 255 (95% CI 143 to 1,184), and in the 30th to <65th percentile risk group is 963 (95% CI 291 to -754); the number needed to screen could not be estimated in the <30th percentile risk group because of absence of lung cancer deaths. When applied to PLCO intervention arm smokers, compared to the USPSTF criteria, the PLCO(m2012) risk ≥ 0.0151 threshold selected 8.8% fewer individuals for screening (p<0.001) but identified 12.4% more lung cancers (sensitivity 80.1% [95% CI 76.8%-83.0%] versus 71.2% [95% CI 67.6%-74.6%], p<0.001), had fewer false-positives (specificity 66.2% [95% CI 65.7%-66.7%] versus 62.7% [95% CI 62.2%-63.1%], p<0.001), and had higher PPV (4.2% [95% CI 3.9%-4.6%] versus 3.4% [95% CI 3.1%-3.7%], p<0.001). In total, 26% of individuals selected for screening based on USPSTF criteria had risks below the threshold PLCO(m2012) risk ≥ 0.0151. Of PLCO former smokers with quit time >15 y, 8.5% had PLCO(m2012) risk ≥ 0.0151. None of 65,711 PLCO never-smokers had PLCO(m2012) risk ≥ 0.0151. Risks and lung cancers were significantly greater in PLCO smokers aged ≥ 65-80 y than in those aged 55-64 y. This study omitted cost-effectiveness analysis. The USPSTF criteria for CT screening include some low-risk individuals and exclude some high-risk individuals. Use of the PLCO(m2012) risk ≥ 0.0151 criterion can improve screening efficiency. Currently, never-smokers should not be screened. Smokers aged ≥ 65-80 y are a high-risk group who may benefit from screening. Please see later in the article for the Editors' Summary.
Highlights
The National Colorectal and Ovarian Cancer Screening Trial (Lung) Screening Trial (NLST) demonstrated that annual low-dose computed tomography (LDCT) screening reduces lung cancer mortality by 20% when applied to high-risk smokers [1]
Our study aims are as follows: (1) identify a risk threshold for selecting lung cancer screenees based on the PLCOm2012 [11] risk at which mortality rates in the National Lung Screening Trial (NLST) CT screening arm are consistently lower than those in the chest Xray (CXR) screening arm; (2) compare performance of U.S Preventive Services Task Force (USPSTF) versus PLCOm2012 risk criteria for selecting screenees, based on lung cancer incidence and mortality; (3) as an alternate PLCOm2012 risk threshold, estimate the PLCOm2012 risk that selects a proportion of smokers equal to that selected by USPSTF criteria; (4) determine whether high-risk never-smokers exceed screening risk thresholds and might be considered for screening; and (5) compare the PLCOm2012 risks and lung cancer rates in high-risk PLCO smokers aged 54–64 y versus $65–80 y
Risk Threshold for Screening Selection Lung cancer mortality rates by NLST intervention arm and by decile of PLCOm2012 risk are presented in Figure 1 and Table 1
Summary
The National Lung Screening Trial (NLST) demonstrated that annual low-dose computed tomography (LDCT) screening reduces lung cancer mortality by 20% when applied to high-risk smokers (age 55–74 y, $30 pack-years, and ,15 y of quit time [for former smokers, time since ceasing smoking]) [1]. The U.S Preventive Services Task Force (USPSTF) recommends annual screening of high-risk individuals, i.e., those who are 55–80 y, have smoked $30 pack-years, and have ,15 y of smoking quit time [9]. Some of these criteria, which are similar to the NLST criteria, were based on microsimulation models developed by the Cancer Intervention and Surveillance Modeling Network (CISNET) lung group [10]. Important issues regarding selection of individuals for lung cancer screening remain It is unclear at what risk individuals should be screened, how efficient the USPSTF criteria are compared to model-based risk criteria, and into what risk threshold USPSTF recommendations translate. Because most lung cancers are not detected until they are advanced, less than 17% of people diagnosed with lung cancer survive for five years
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