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

(NCI, 2021)Overall mortality rates for lung and bronchus cancer have decreased over the past decade, averaging 3.8% each year over 20102019 (NCI, 2021). The majority of cases are still diagnosed at a late stage with a low five-year relative survival (NCI, 2021). Most patients diagnosed with lung cancer present with distant or metastatic disease; less than 20% are diagnosed with localized (i.e., stage 1) disease (NCI, 2021). Patients with localized disease have a 60% five-year survival rate, compared with 33% for those with regional spread to lymph nodes and 6% for those with distant pulmonary metastases (NCI,2021).Lung cancer has a generally poor prognosis, with overall observed five-year relative survival of 22.1% in 2013 (NCI, 2021). However, early-stage lung cancer has a better prognosis and is more amenable to treatment (USPSTF, Krist; 2021). By leading to earlier detection and treatment, screening for lung cancer can give patients a greater chance for cure (USPSTF, Krist; 2021).(Stage and Survival for Lung Cancer; NCI, 2021)Lung cancer is a proliferation of malignant cells arising in the tissues or airways of the lungs. Lung cancer has traditionally been classified into 2 major categories based on cell type and immunohistochemical and molecular characteristics: (1) nonsmall cell lung cancer (NSCLC), which collectively comprises adenocarcinoma, squamous cell carcinoma, and large cell carcinoma (ACS, Lung Cancer; 2019), and (2) small cell lung cancer, which is more aggressive and has worse survival rates (Jonas, 2021; Travis, 2015; USPSTF, Krist; 2021). About 80% to 85% of lung cancers are non-small cell lung cancer (NSCLC) (ACS, Lung Cancer; 2019). These subtypes, which start from different types of lung cells are grouped together as NSCLC because their treatment and prognoses (outlook) are often similar. About 10% to 15% of all lung cancers are small cell lung cancer (SCLC) (ACS, Lung Cancer; 2019). This type of lung cancer tends to grow and spread faster than NSCLC. About 70% of people with SCLC will have cancer that has already spread at the time they are diagnosed (ACS, Lung Cancer; 2019). Screening is aimed at early detection of NSCLC rather than small cell lung cancer because the latter is much less common and typically spreads too quickly to be reliably detected at an early, potentially curable stage by screening (USPSTF, Krist; 2021).The most important risk factor for lung cancer is smoking (Alberg, 2013). The risk of developing lung cancer is largely driven by age and smoking status, with smoking estimated to account for nearly 90% of all lung cancer cases (ACS, Risk Factors, 2019; Alberg, 2013; Siegel, 2021; USPSTF, Krist, 2021), with a relative risk of developing lung cancer approximately 20-fold higher in smokers than in nonsmokers (Samet, 1992). Just as important, older age is also associated with increasing incidence of lung cancer (USPSTF, Krist; 2021). Other risk factors for lung cancer include environmental exposures such as radon and asbestos, radiation therapy, other (noncancer) lung diseases, race/ethnicity, and family history (ACS, Risk Factors, 2019; Jonas, 2021). About 80% of lung cancer deaths are thought to result from smoking (ACS, Risk Factors; 2019).Computed TomographyThe National Institutes of Health (NIH) National Cancer Institute (NCI) describes computed tomography (CT) as an imaging procedure that uses special x-ray equipment to create detailed pictures, or scans, of areas inside the body. It is sometimes called computerized tomography or computerized axial tomography (CAT). . . . Each picture created during a CT procedure shows the organs, bones, and other tissues in a thin slice of the body. The entire series of pictures produced in CT is like a loaf of sliced breadyou can look at each slice individually (2-dimensional pictures), or you can look at the whole loaf (a 3-dimensional picture). Computer programs are used to create both types of pictures. Modern CT machines take continuous pictures in a helical (or spiral) fashion rather than taking a series of pictures of individual slices of the body, as the original CT machines did. Helical CT (also called spiral CT) has several advantages over older CT techniques: it is faster, produces better quality 3-D pictures of areas inside the body, and may detect small abnormalities better (NIH, NCI; 2019).United States Preventive Services Task Force (USPSTF)In 2021, the most recent recommendation was released to update its 2013 recommendation: The USPSTF recommends annual screening for lung cancer with 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. Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery. (B recommendation) (USPSTF, Krist; 2021).The USPSTF assigns one of five letter grades to each of its recommendations (A, B, C, D, I). The following tables from Moyer et al. (2014) on behalf of the USPSTF provide the current grade definitions and descriptions of levels of certainty after July 2012.(Moyer, 2014)(Moyer, 2014)III. History of Medicare CoveragePursuant to 1861(ddd)(1) of the Act, the Secretary may add coverage of "additional preventive services" if certain statutory requirements are met. Specifically, the definition of additional preventive services permits coverage under Medicare Part B for certain services that were not already included as preventive services and if the Secretary determines through the national coverage determination process (as defined in section 1869(f)(1)(B) of the Act) that these services are all of the following:(1) Reasonable and necessary for the prevention or early detection of illness or disability.(2) Recommended with a grade of A or B by the United States Preventive Services Task Force.(3) Appropriate for individuals entitled to benefits under Part A or enrolled under Part B.We have established regulations implementing this statute that are codified at 42 CFR  410.64.CMS issued an NCD on February 5, 2015 establishing coverage for lung cancer screeningwith LDCT. The NCD includes beneficiary eligibility criteria, a counseling and shared decision-making visit, reading radiologist eligibility criteria, and radiology imaging facility eligibility criteria.The policy is codified in section 210.14 of the Medicare National Coverage Determinations (NCD) Manual (Pub. 100-03). Section 210.14 of the NCD Manual is included in Appendix C.A. Current RequestCMS received a complete, formal joint request to reconsider the Lung Cancer Screening with Low Dose Computed Tomography (LDCT) NCD from the GO2Foundation for Lung Cancer, The Society of Thoracic Surgeons, and American College of Radiology (ACR).The request letter is available athttps://www.cms.gov/medicare-coverage-database/view/ncacal-tracking-sheet.aspx?ncaid=304B. Benefit CategoryMedicare is a defined benefit program. For an item or service to be covered by the Medicare program, it must fall within one of the statutorily defined benefit categories outlined in the Act. CMS is authorized to cover "additional preventive services" if certain statutory requirements are met as provided under 1861(ddd) of the Social Security Act.IV. Timeline of Recent ActivitiesDateActions TakenMay 18, 2021CMS initiates this national coverage analysis. A 30-day public comment period begins.June 17, 2021First public comment period ends. CMS receives 170 comments.November 17, 2021Proposed Decision Memorandum posted. 30-day public comment period begins.December 17, 2021Second public comment period ends.  CMS receives 49 public comments.V. Food and Drug Administration (FDA) StatusCT imaging systems and post-processing software go through the 510(k) process at the FDA to obtain clearance for commercial distribution. To obtain 510(k) clearance, the sponsor must demonstrate that the device is substantially equivalent in terms of its intended use, technological characteristics, and safety and effectiveness to CT systems previously cleared or on the market prior to the 1976 Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (FDCA) that do not require approval of a premarket approval application (PMA). FDA has authorized CT systems with indications for low-dose lung cancer screening.Counseling services are not generally under the purview of the FDA.VI. General Methodological PrinciplesWhen making national coverage determinations concerning additional preventive services, CMS applies the statutory criteria in  1861(ddd) of the Social Security Act and regulations at 42 CFR 410.64, and evaluates relevant clinical evidence to determine whether or not the service is reasonable and necessary for the prevention or early detection of illness or disability, is recommended with a grade of A or B by the USPSTF, and is appropriate for individuals entitled to benefits under Part A or enrolled under Part B of the Medicare program.VII. EvidenceThe evidence summarized in this section includes the peer-reviewed, published clinical research pertinent to lung cancer screening with LDCT. Our assessment focuses on the key evidence questions below.1. Evidence QuestionsQuestion 1: Is the evidence sufficient to determine that screening for lung cancer with low dose computed tomography is recommended with a grade of A or B by the United States Preventive Services Task Force?Question 2: Is the evidence sufficient to determine that screening for lung cancer with low dose computed tomography is reasonable and necessary for the prevention or early detection of illness or disability?Question 3: Is the evidence sufficient to determine that screening for lung cancer with low dose computed tomography is appropriate for Medicare beneficiaries?2. External Technology AssessmentsCMS did not request an external technology assessment (TA) on this issue.3. Internal Technology AssessmentLiterature Search MethodsCMS searched PubMed for publications from the period of August 2014 to July 2021. We chose the starting search date as August 2014 since the literature search for the 2015 National Coverage Determinations internal technology assessment on screening for lung cancer with low dose CT ended in August 2014. General keywords included low dose computed tomography, screening, mortality, and lung cancer. Publications that presented original human clinical data on screening with low dose CT for lung cancer were considered. Keywords for the search included low dose computed tomography, low dose CT, LDCT, screening, survival, mortality, death, and lung cancer. CMS staff searched the bibliographies of relevant publications for other pertinent studies. Abstracts, meeting presentations, reviews, animal studies, publications on emphysema and asbestos, cost analyses, microsimulation modeling studies, mechanistic biomarker studies, and non-English language publications were excluded. Studies with fewer than 10 cases and those not involving human subjects were excluded. The reviewed evidence was gathered from articles submitted by the requester, and from the public comments and the PubMed literature search.Articles were included if they conformed to the following eligibility criteria:Inclusion criteria:Studies using low dose computed tomography (low dose CT) for lung cancer screeningArticles published in scientific journalsTechnology assessments, guidelines, consensus statements, or meta-analysesEnglish languageAdultHumanLiterature from United States, Canada, the United Kingdom, Europe, Australia, China and other Southeast Asian countriesExclusion criteria:Non-English language articlesTechnical, nonclinical articles (e.g., animal, biomechanical, cadaver)Conference abstracts, meeting presentationsStudies conducted outside the countries listed aboveStudies published before 2014Studies with less than 10 participantsStudies not related to low dose computed tomographyStudies not related to lung cancerTable 1. Age Eligibility Criteria for Low Dose CT Randomized Controlled TrialsFirst Author (year published), Study Acronym, Study Design, Population: Country, Overall Sample Size (n)Age Inclusion Criteria (years)Age Distribution in Screening Study Population (mean, lowest and highest age groups, frequency; n, years)Race (percent)Women (percent)Timing: Follow Up Duration (mean; years)Outcome: Lung Cancer Mortality: Low Dose CT Arm Compared Control Arm (HR, RR, or OR, 95% CI; p value)Becker (2020) LUSI (RCT) Germany (4,052)50 to 69Median: 5550-54: 46.4% (942/2029)65-69: 11.1% (225/2029)Not shown35.3%8.8  yr (median)HR: 0.74 (0.46 1.19; p = 0.21)HR women: 0.31 (0.10 0.96, p = 0.04)