NCA - Screening for Lung Cancer with Low Dose Computed Tomography (LDCT) (CAG-00439R) - Decision Memo

The American Academy of Family Physicians gives the clinical preventive services recommendation for lung cancer screening in adults a B grade recommendation. The AAFP supports the United States Preventive Services Task Force (USPSTF) recommendation for annual screening for lung cancer with low-dose computed tomography (LDCT) in adults aged 50 to 80 years who have a 20 pack-year smoking history and currently smoke or have quit within the past 15 years (AAFP, 2021). Thus, the American Academy of Family Physicians recommends starting screening at age 50 years.We find that the human clinical evidence is sufficient to conclude that lung cancer screening with low dose CT is reasonable and necessary for prevention or early detection of illness or disability, for Medicare beneficiaries with the specific eligibility criterion for starting low dose CT screening at age 50 years. This approach to broadening the starting age for lung cancer screening from 55 to 50 years is consistent with the USPSTF grade B recommendation.Changing Stopping Age From 77 years to 80 yearsThe current 2021 USPSTF lung cancer screening statement recommends a stopping age for screening of 80 years (USPSTF, Krist; 2021). This stopping age is the same as the 2013 USPSTF recommendation of stopping screening at age 80 years (Moyer, USPSTF; 2014). However, the 2015 NCD on Screening for Lung Cancer with LDCT had the stopping age for screening at 77 years because there were no trial data or evidence on adults over 77 years (CAG-00439N; CMS, 2015). For this reconsideration, we will assess the recently updated trial data published from 2014 to the present for evidence of the effect of screening with low dose CT among persons age 77 years to 80 years.Many low dose CT studies did not include persons age 77- to 80-years-old at time of enrollment into the study. For the extended follow up analysis of the NLST trial, the inclusion criterion for age was 55 to 74 years, so the upper age criterion was 74 years (NLST Research Team, 2019). The upper age group at randomization was 70- to 74-years-old and consisted of 8.8% (2,354/26,722) of the low dose CT screening arm in the NLST trial (NLST Research Team, 2019). Persons age 74 to 80 years were excluded from the NLST study.For the NELSON study, the inclusion criterion for age was 50 to 74 years (de Koning, 2020). At randomization, the median age of the male participants was 58 years in the low dose CT screening group (interquartile range, 55 to 63 in the screening group) and while the highest age group of > 75years comprised 0.6% (40/6,560) of the screening group, the age range for men was from 46 years to 76 years (de Koning, 2020). The NELSON study did not include persons 77- to 80-years-old.For the ITALUNG study, one of several small European randomized controlled clinical trials of low dose CT, the inclusion criterion for age was 55 to 69 years (Paci, 2017), so the upper age limit was 69 years. In the active group, the mean age at entry was 60.9 years with the uppermost age group of > 69 years comprising 0.3% (5/1,613) of the LDCT study population (Paci, 2017). Persons who were 70- to 80-years-old were not included in the ITALUNG study. The inclusion criterion for age in the LUSI study was 50 to 69 years (Becker, 2020). The median age in the intervention arm of the LUSI study was 55 years and the upper age group 65 to 69 years comprised 11.1% (225/2,029) of the intervention arm (Becker, 2020). The LUSI study did not include persons 70- to 80-years-old. For the MILD study, the inclusion criterion for age was 49 to 75 years (Pastorino, Silva; Prolonged, July, 2019). The median age of the intervention arm was 58 years and the upper age group of  70 years comprised 3.8% (90/2,376) of the intervention arm in the MILD study (Pastorino, Silva; Prolonged, July, 2019). The MILD study excluded persons 76- to 80-years-old.For the DLCST study, the inclusion criterion for age was 50 to 70 years (Wille, 2016). The mean age of the screening group at randomization was 57.9  standard deviation of 4.8 (Wille, 2016). The upper limit of the inclusion criteria included persons equal to or less than 70 years-old. Thus, the DLCST study did not include persons 71 to 80 years-old. For the UKLS study, the inclusion criterion for age was 5075 years (n = 4,055, with 4,061 enrolled and 6 not randomized) at high risk of lung cancer (Field; May, 2016). The uppermost age group was 71- to 75-years-old (Field; May, 2016). For the study population (n = 4,061 enrolled with 6 not randomized), 22.4% were age 71 to 75 years and the mean age of the screened arm was 67.1  4.1 years (Field; May, 2016). Thus, the UKLS study excluded persons 76- to 80-years-old.For the small European DANTE study, the eligibility criterion for age was 60 to 74 years (Infante, 2015). The upper limit of the age criterion was 74 years, which excludes persons 77 to 80 years. In the low dose CT arm, the median age was 64.0 years (interquartile range: 5 years) and the mean age was 64.6 years (95% CI: 64.3-64.8) (Infante, 2015). The DANTE study excluded persons 75- to 80-years-old. The retrospective analysis of the small COSMOS study enrolled high risk asymptomatic smokers aged 50 and older, who were current or former smokers (20 pack-years) (Rampinelli, 2017). For the COSMOS study, the  65 years age group comprised 12.6% (658/5203) of the trial participants (Rampinelli, 2017). The COSMOS study does not appear to have persons 77- to 80-years-old in the study population. For the small LSS feasibility study (n = 3,318) conducted in the United States, the eligibility criterion for age was 55 to 74 years (Doroudi, 2018). With the upper limit of the age criterion being 74 years, the LSS study excluded persons 75 to 80 years.Thus, none of the ten randomized controlled clinical trials, including the COSMOS, DANTE, DLCST, ITALUNG, LSS, LUSI, MILD,NELSON, NLST, and UKLS studies, had persons age 77- to 80-years-old in the study populations.In our literature search, one observational study, study by Liang et al., (2019 included individuals in age categories beyond 77 years, categorized as 75 to 79 years, 80 to 84 years, and greater than or equal to 85 years. The Liang et al., (2019) study used official cancer registry data from Shanghai municipality and its two districts with different levels of accessibility for low dose CT, defined as urban versus suburban access, to assess the potential effect of low dose CT on lung cancer incidence and mortality, but the study had no patient-level data on low dose CT. A major limitation reported by the study authors was that they could not determine which patients were diagnosed through LDCT screening, or how many people were screened in the different regions (Liang, 2019). In addition, the Liang (2019) study did not follow individuals over time and had no prospective follow up information on outcomes such as lung cancer mortality. As a result, the study did not calculate lung cancer mortality  as a hazard ratio or a rate ratio using a survival function. Thus, the Liang (2019) cancer registry  study, while including persons beyond 77 years-old, was excluded from the analysis because it was not a prospective randomized controlled trial of using low dose CT to screen for lung cancer and it did not have information on whether an individual was screened with low dose CT.Our findings on the lack of evidence on adults over 77 years are consistent with our 2015 decision memo for Screening for Lung Cancer with Low Dose Computed Tomography (LDCT) (CAG-00439N; CMS, 2015).Overall, there are no lung cancer screening trial data or evidence on adults over 77 years. There is insufficient evidence to determine if these patients over 77 years would benefit from low dose CT screening for lung cancer. There is no relevant published human clinical study literature regarding the use of low dose CT in persons age 77- to 80-years-old. We find the human clinical evidence is insufficient to determine that screening for lung cancer with low dose CT is reasonable and necessary for the prevention or early detection of illness or disability for the population of 77- to 80-years-old who are eligible for low dose CT. The study results do not show sufficient evidence to change the eligibility criterion for the age to stop lung cancer screening with low dose CT. Thus, we find that the evidence is not sufficient to conclude that lung cancer screening is reasonable and necessary for Medicare beneficiaries with the specific eligibility criterion for the stopping age of 80 years. The Medicare beneficiary eligibility criterion for stopping age will not be changed and will remain at 77 years-old.Among the organizations making recommendations for the selection of individuals for lung cancer screening, the American College of Chest Physicians (CHEST) has two recommendations. 1. For asymptomatic individuals age 55 to 77 who have smoked 30 pack- years or more and either continue to smoke or have quit within the past 15 years, we recommend that annual screening with low-dose CT should be offered. (Strong recommendation, moderate-quality evidence). 2. For asymptomatic individuals who do not meet the smoking and/or age criteria in Recommendation #1, are age 50 to 80, have smoked 20 pack-years or more and either continue to smoke or have quit within the past 15 years, we suggest that annual screening with low-dose CT should be offered. (Weak recommendation, moderate-quality evidence) (Mazzone, Panel Report 2021). In the American College of Chest Physicians (CHEST) guidelines for low dose CT lung cancer screening (Mazzone, Panel Report 2021), they presented no data on the effect of screening cessation between age 77 and 80 years on lung cancer mortality. The CHEST guidelines meta-analysis stops the age at screening cessation at 75 years and has no data beyond the stopping age of 76 or more years.In the National Comprehensive Cancer Network (NCCN), Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Lung Cancer Screening Version 1.2022, the NCCN Lung Cancer Screening Panel defined the risk status of high risk as age  50 years and  20 pack-year history of smoking with these high-risk persons candidates for low dose CT (LDCT) screening (category 1) where shared patient/provider decision-making is recommended, including a discussion of benefits/risks (Wood, NCCN; 2021). Further, in the discussion of extending low dose CT screening beyond 77 years that is being updated in the most recent NCCN guidelines Version 1. 2022 (Wood, NCCN; 2021), no randomized controlled trial data were presented that showed whether low dose CT screening in persons age 77 or more years had an effect on lung cancer mortality, and so the evidence base for extending the eligibility criterion for low dose CT screening beyond 77 years does not appear to have randomized controlled trial evidence. Thus, in the updated National Comprehensive Cancer Network (NCCN) guidelines Version 1.2022, the eligibility criterion for age has no upper age limit in the low dose CT screening algorithm, and therefore, does not include a stopping age for low dose CT screening.In summary of their recommendations, the American College of Radiology Appropriateness Criteria expert panel concluded that for Variant 1: Lung cancer screening with low-dose CT chest without IV contrast is usually appropriate in patients 55 to 80 years of age and 30 or more packs per year smoking history and currently smoke or have quit within the past 15 years. Variant 2: The panel did not agree on recommending lung cancer screening with low dose CT chest without IV contrast in patients 50 years of age or older and 20 or more packs per year history of smoking plus one additional risk factor. There is insufficient medical literature to conclude whether or not these patients would benefit from CT screening for lung cancer. Screening in this patient population is controversial but may be appropriate. Variant 3: Lung cancer screening is usually not appropriate in patients younger than 50 years of age or older than 80 years of age or in patients of any age with less than 20 packs per year history of smoking and no additional risk factors (Donnelly, 2018). Thus, the American College of Radiology recommends stopping screening at age 80 years.