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

Additionally, the authors reported that the annual incidence of lung cancer in our control group was only half what we expected (i.e., 0.27% instead of 0.50%); thus, the study was underpowered, and concluded that the limited statistical power of this trial does not allow a conclusive statement about the efficacy of lung cancer screening but go on to say that nevertheless, our results support risk stratification with a focus on age, smoking history, and obstructive lung disease when selecting candidates for lung cancer screening (Wille, 2016). Thus, the DLCST study (Wille, 2016) did not show age-specific subgroup data on the effect of low dose CT screening on lung cancer deaths among 50- to 54-year-old persons, even though the inclusion criteria for age included persons greater than or equal to age 50 years, and the DLCST study results did not show a statistically significant lowering of lung cancer mortality in the low dose CT group.Even though two small European studies included persons age 50- to 54-years-old, neither the UKLS nor the COSMOS study had results for lung cancer mortality. The United Kingdom Lung Cancer Screening pilot study (UKLS) trial by Field et al., (May, 2016) was a pilot randomized controlled trial comparing a single thoracic low dose CT scan intervention with usual care that randomized individuals aged 5075 years (n = 4,055, with 4,061 enrolled and 6 not randomized) at high risk of lung cancer. The mean age of the screened arm was 67.1  4.1 years. For the study population (n = 4,061 enrolled with 6 not randomized), 29 (0.7%) were age 50 to 55 years. A total of 1994 participants underwent CT scanning: 42 participants (2.1%) were diagnosed with lung cancer. The mean age at trial recruitment for the cancer patients was 66.9 years (median 67 years; range 5575 years). No lung cancer mortality data were presented, and there were no age-stratified analyses for those diagnosed with lung cancer. The authors reported that the UKLS pilot is insufficiently powered to demonstrate a reduction in mortality (Field; May, 2016). The study authors concluded that [l]ung cancer has been detected in 2.1% of people screened and that the specific successes include the demonstration that a population-based lung cancer screening trial can be undertaken in the UK, using a risk-based prediction model to select participants (Field; May, 2016).The aim of the Rampinelli (2017) study was to evaluate the cumulative radiation exposure and lifetime attributable risk of cancer incidence associated with low dose CT in a retrospective secondary analysis of data from a 10-year non-randomized observational lung cancer screening program, the Continuous Observation of Smoking Subjects (COSMOS) study. The single center COSMOS study in Italy enrolled high risk asymptomatic smokers aged 50 and older, who were current or former smokers (20 pack-years). The 50- to 54-year-old age group consisted of 34.4% (606/1759) women. The retrospective study included stratified analyses for the 50- to 54-year-old age group on the lifetime attributable risk of lung cancer and major cancers after 10 years of CT screening, but the COSMOS study by Rampinelli et al., (2017) did not have results for lung cancer-specific mortality data. Neither the UKLS nor the COSMOS study had results for lung cancer mortality. Thus, neither the COSMOS (Rampinelli, 2017) nor the UKLS (Field; May, 2016) studies had results for lung cancer mortality, even though persons age 50- to 54- years-old were included in the study populations.Several low dose CT studies, such as the NLST, did not include persons age 50- to 54-years-old at enrollment into the study. For the extended follow up analysis of the high quality NLST trial, one of the two largest randomized controlled clinical trials of low dose CT, with the other being the NELSON study, the inclusion criterion for age was 55 to 74 years, so the lower age criterion was 55 years (NLST Research Team, 2019). The lowest age group at randomization was the 55- to 59-year-olds which was 42.8% (11,442/26,722) of the low dose CT intervention arm in the NLST trial (NLST Research Team, 2019). Persons age 50 to 54 years were excluded from the NLST study.For the ITALUNG study, one of several small European randomized controlled clinical trials of low dose CT that excluded persons age 50- to 54-years-old, the inclusion criterion for age was 55 to 69 years (Paci, 2017), so the lower age limit was 55 years. In the active group, the mean age at entry was 60.9 years with the lowest age group of < 55 years comprising 3% (53/1.613) of the LDCT study population (Paci, 2017). Persons who were 50 to 54 years were not included in the ITALUNG study. For the small European DANTE study, the eligibility criterion for age was 60 to 74 years (Infante, 2015). The lower limit of the age criterion was 60 years, which excludes persons 50 to 54years. 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 results did not show the baseline age distribution for the study population stratified by age group, such as 50 to 54 years. The lung cancer mortality analyses of the DANTE study were not stratified by age group, such as 50 to 54 years. The DANTE study excluded persons 50- to 54-years-old. 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 lower limit of the age criterion being 55 years, the LSS study excluded persons 50 to 54 years.Overall, based primarily on the NELSON, LUSI, and MILD study results, we find the human clinical evidence is sufficient 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 50- to 54-years-olds who are eligible for low dose CT. Given the limitations of the three studies, the overall evidence from the stratified results of the LUSI study and the overall results of the MILD and NELSON studies suggest a clinically significant lowering of lung cancer deaths among persons who were age 50 to 54 years who received low dose CT lung cancer screening compared to those who had no screening. The evidence suggests that lowering the starting age for low dose CT screening from 55 years to 50 years will continue to show benefit by reducing lung cancer deaths for women and very likely for men. The study results show sufficient evidence to lower the starting age for lung cancer screening with low dose CT. The evidence is sufficient for broadening the age eligibility criteria for lung cancer screening with low dose CT. Thus, with these limitations, we find that the evidence is sufficient to conclude that this approach to broadening the recommended population for lung cancer screening is reasonable and necessary for the prevention or early detection of illness or disability among Medicare beneficiaries with the specific eligibility criterion for starting age of screening set at 50 years.The 2021 USPSTF recommendation on lung cancer screening now recommends that people start screening at age 50 (USPSTF, Krist; 2021), rather than age 55 years. As reported by the authors of the 2021 USPSTF evidence review by Jonas et al. (2021), NLST and NELSON results are generally applicable to high-risk current and former smokers aged 50 to 74 years, but participants were younger, more highly educated, less likely to be current smokers than the US screening-eligible population, and had limited racial and ethnic diversity. The general US population eligible for lung cancer screening may be less likely to benefit from early detection compared with NLST and NELSON participants because they face a high risk of death from competing causes, such as heart disease and stroke. Data from the 2012 Health and Retirement Study showed a lower 5-year survival rate and life expectancy in screening-eligible persons compared with NLST participants (Jonas, 2021). Consistent with the USPSTF grade B recommendation, our recommended screening population for starting age allows lung cancer screening to be reasonable and necessary for Medicare beneficiaries.Among the societal 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). Thus, for the lower age limit for starting low dose CT screening between 50 and 54 years, the American College of Chest Physicians guidelines only suggest low dose CT since this is a weak recommendation, and so it is not recommended since it is not a strongrecommendation.In the updated 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). For NCCN categories of evidence and consensus, Category 1 is defined as based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate (Wood, NCCN; 2021). Thus, the updated NCCN guidelines recommend starting screening at age 50 years.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 starting screening at age 55 years.The American Cancer Society 2013 guideline recommends that clinicians with access to high-volume, high-quality lung cancer screening and treatment centers should initiate a discussion about screening with apparently healthy patients aged 55 years to 74 years who have at least a 30 [or more]pack-year smoking history and who currently smoke or have quit within the past 15 years (Wender, 2013). This American Cancer Society guideline was published around the time of the previous 2013 USPSTF lung cancer screening recommendation statement. Thus, the American Cancer Society recommends starting screening at age 55 years. However, the 2013 American Cancer Society guideline is being updated and, in the meantime, the American Cancer Society recommends yearly lung cancer screening with low dose CT scans for people who: are 50 to 80 years old and in fairly good health, currently smoke or have quit in the past 15 years, and have at least a 20 pack-year smoking history.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.