MTE 27.01 Who Should be Screened for Lung Cancer?

Abstract

The National Lung Screening Trial (NLST) demonstrated that screening for lung cancer could reduce lung cancer (LC) mortality by 20%.1 Screening with low-dose CT (LDCT) resulted in more early stage lung cancers and fewer late-stage cancers as compared to chest X-ray screening. It has been estimated that 12,000 lung cancer deaths could be averted each year if all eligible Americans were to undergo LDCT screening.2 An Italian screening study with LDCT reported that stopping smoking reduces overall mortality by 39% compared with current smokers.3 Tanner and associates also reported a 20% LC mortality reduction in the NLST in the chest X-ray arm (control arm) in the absence of smoking for 7 years.4 The maximum mortality benefit was seen in the absence of smoking in combination with LDCT that resulted in a LC mortality reduction of 38% (HR=0.62). Accordingly, current-screening programs must include tobacco cessation counseling and treatment to current smokers.5 The US Preventive Services Task Force has approved LDCT screening in high-risk individuals (asymptomatic persons aged 55 to 80 years who have a 30-pack-year or more smoking history and have quit within the past 15 years).6 However, from 2010-2015 less than 5% per year of those eligible are currently undergoing LDCT screening. Of the 6.8 million smokers eligible for LDCT screening, only 262,700 received it.7 In the last two years a large number of centers have ramped up their screening programs in the US. Another issue is that of all lung cancers patients in the United States only 30-40% of these individuals were actually eligible for LDCT screening based on the NLST criteria for screening.8 Tammemagi et al developed an LC-risk-prediction model based on the PLCO (Prostate, Lung, Colon, Ovarian) screening trial.9 At a six-year LC risk of ≥1.5%, this risk prediction model detected 12% more LC and screened 8.8% fewer individuals than those using the NSLC screening criteria.10 The number needed to screen to detect one LC was 255 with this model as compared with 320 in the NLST. None of the never-smokers in the PLCO trial had a risk of >1.5%. Do not screen never-smokers! In an effort to detect more lung cancers at an earlier stage, additional risk factors need to be included in screening programs and evaluated for their efficacy. Young and colleagues evaluated a subset of the NLST participants who had pulmonary function testing (PFT) and observed a two-fold increase in lung cancer incidence with COPD.11 There was a linear relationship between increasing severity of airflow limitation and risk of lung cancer.12 The heritability of lung cancer is not well explained. The OncoArray Consortium has identified 18 genetic susceptibility loci for LC across histological types.13 Dr. Stephen Lam in Vancouver, BC is testing this 18-gene array as a risk factor in an international screening trial. The European Study of Cohorts of Air Pollution Effects (ESCAPE) identified particle matter (PM 10 and PM 2.5) as having significant association with LC risk (HR1.22 and 1.18 respectively).14 The hazard ratios (HR) associated with adenocarcinoma was 1.51 and 1.55 respectively. Satellites are able to measure air pollution and have good correlation with simultaneous ground measurements (accessed 8/4/2017). There is extensive research into biomarkers for risk of lung cancer that might be of use in screening for LC or in identifying risk of malignancy in indeterminate pulmonary nodules. Sources of biomarkers to date have included breath, sputum, urine and blood. Categories of blood biomarkers have included micro-RNA, proteins, circulating tumor DNA and autoantibodies. A randomized prospective trial (RCT) in Scotland is evaluating an autoantibody panel against tumor antigens for early detection of LC.15 The trial randomized 12,000 high-risk participants to the blood test alone or routine care (no screening). Those with a positive blood test undergo a CT chest scan. Results of this RTC should be available in late 2018. If we (IASLC) are going to decrease the mortality of lung cancer then we must promote tobacco use intervention and implement LC screening so that more LCs are detected in an early and more curable stage. The optimal paradigm for screening has yet to be developed and is likely to vary in different countries. The NLST was a starting point and reveals that is can be accomplished. Continued innovations and research are required. 1. The National Lung Cancer Screening Trial Research Team. NEJM (2011); 365:395-409 2. Ma et al. Cancer (2013); 119:1381-5 3. Pastorino et al. J Thorac Oncol (2016); 11:693-699 4. Tanner et al. Amer J Resp Crit Care Med (2016); 193:534-541 5. Tammemagi et al. JNCI (2014); 106:doi.1043/jnci/dju168 6. Moyer et al. Ann Int Med (2014); 160:330-338 7. Jemal and Fedewa. JAMA Oncol, published online February 2, 2017 8. Wang et al. JAMA (2015); 313:853-855 9. Tammemagi et al. NEJM (2013); 368:728-736 10. Tammemagi et al. PLOS (2014); 11e 1001764 11. Young et al. Amer J Resp Crit Care Med (2015); 192:1060-1067 12. Hopkins et al. Annals Amer Thorac Society, published online January 11, 2017. 13. McKay et al. Nature Genetics (2017); 49:1126-1132 14. Raaschou-Nielsen et al. Lancet Oncol (2013); 14:813-822 15) Sullivan et al. BMC Cancer (2017); 17:187-196. Screening, Risk Assessment