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

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.Similarly, 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 stopping screening at age 80 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). 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.We find that the human clinical evidence is not sufficient to conclude that lung cancer screening with low dose CT is reasonable and necessary for Medicare beneficiaries with the specific eligibility criterion for stopping low dose CT screening at age 80 years. The Medicare beneficiary eligibility criterion for stopping age will not be changed and will remain at 77 years-old.Lowering Pack-Year Smoking History From 30 Pack-Years to 20 Pack-YearsThe 2021 USPSTF lung cancer screening statement recommends annual lung cancer screening with low dose CT for adults who have a 20 pack-year smoking history (USPSTF, Krist; 2021). The current updated 2021 USPSTF recommendation reduces the pack-years of smoking history that makes someone eligible for screening from 30 pack-years to 20 pack-years. Thus, the pack-year eligibility criterion was lowered from 30 pack-years in the previous 2013 USPSTF recommendation (Moyer, USPSTF; 2014) to 20 pack-year smoking history in the current updated recommendation. For this reconsideration, we will assess the recently updated trial data published from 2014 to the present for evidence on the beneficial effect of screening with low dose CT among persons who have a smoking history of 20 to 29 pack-years.The MILD study (Pastorino, Silva, Sestini; 2019) defined the enrollment eligibility criterion for current smokers as  20 pack-years (Pastorino, Silva, Sestini; 2019). In the intervention arm, 21.9% (521/2,376) had < 30 pack-years of cigarette smoking and the median pack-years was 39 pack-years of smoking (Pastorino, 2019). Taking into account the minimum enrollment criterion for smokers of at least 20 pack-years, 21.9% of the intervention arm smoked 20 to 29 pack-years. In the MILD study, the low dose CT arm showed a significant 39% reduced risk of lung cancer mortality at 10 years compared to the control arm (hazard ratio = 0.61; 95% CI 0.39  0.95; p = 0.02) with adjustment for age and pack-years (Pastorino, Silva, Sestini; 2019). Even though there was no stratified lung cancer mortality analysis by smoking history subgroups in the number of pack-years, such as 20 to 29 pack-years of smoking cigarettes, the overall study results demonstrated statistically significant reduced lung cancer mortality, 39%, in the low dose CT arm which included persons who smoked between 20 to 29 pack-years with the large subgroup comprising 21.9% of the overall study population. Thus, there is evidence from the MILD study that lowering the smoking history from 30 pack-years to 20 pack-years would likely continue to reduce lung cancer deaths among persons who are screened for lung cancer with low dose CT.In the good quality NELSON study, the eligibility inclusion criterion for smoking history was persons who had smoked >15 cigarettes a day for > 25 years or >10 cigarettes a day for >30 years (de Koning, 2020). In pack-years, >15 cigarettes a day for > 25 years is equivalent to > 19 pack-years, and >10 cigarettes a day for >30 years is equivalent to >15 pack-years. Persons who smoked 20 to 29 pack-years were included in the NELSON study. Among the male participants in the screening group for the NELSON study, the median pack-year of smoking was 38.0 (interquartile range: 29.7  49.5) with a range of pack-years from 0.4 to 159.5 (de Koning, 2020). The specific number of pack-years smoked by the male participants is not shown in the NELSON study results. However, the NELSON study reported on the number of cigarettes smoked per day and the duration of smoking in years for the male participants.Because the number of pack-years smoked by participants in the NELSON study was not used to define smoking history, it is necessary to show how to convert the number of cigarettes smoked per day and the duration of smoking to pack-years smoked. Pack-years, or packs per years, are calculated by multiplying the number of packs of cigarettes smoked per day by the number of years the person has smoked, with a pack equal to 20 cigarettes. If a person has smoked a pack a day for the last 20 years, or two packs a day for the last 10 years, the person has a smoking history of 20 pack-years. Equivalently, if a person has smoked 20 cigarettes a day, which is one pack a day, for the last 20 years; or 40 cigarettes a day, which is two packs a day, for the last 10 years, the person has a smoking history of 20 pack-years.Among the male participants in the screening group (n = 6,583) for the NELSON study, 28.3% (1,859/6,565) smoked 16 to 20 cigarettes a day, which is about one pack a day, and 0.4% (25/6,563)had a duration of smoking of  25 years which includes an unspecified number of persons smoking for the last 20 years which is below 0.4%, meaning that an undetermined but likely small but non zero number of men smoked about one pack per day for perhaps 20 years which approximates a 20 pack-year smoking history. Equivalently to a 20 pack-year history, 6.9% (454/6,565) smoked 31 to 40 cigarettes a day, which is about two packs a day, and 0.4% (25/6,563) had a duration of smoking of  25 years which includes an unspecified number of persons smoking for the last 10 years which is below 0.4% (de Koning, 2020). Because the NELSON study results did not include the pack-year smoking history stratified by the number of pack-years, it is not known exactly how many men had a smoking history of 20 to 29 pack-years. However, the NELSON study included men who smoked about one pack per day (28.3%) and about two packs per day (6.9%), and those men smoked for  25 years (0.4%) with some of them, less than 0.4%, likely smoking for the last 20 years at one pack per day or 10 years at two packs per day, which would amount to a 20 pack-year smoking history. In addition, the lower limit of the range of pack-years of smoking was 0.4, so the range of pack-years of smoking encompasses 20 to 29 pack-years. Thus, while the exact number of men smoking 20 to 29 pack-years is not known, men with a smoking history of 20 to 29 pack-years would very likely have been included in the NELSON study, though the precise number is likely to be small but not zero. Additionally, the eligibility criterion for smoking history permitted persons who smoked 20 to 29 pack-years to be included in the NELSON study.For the NELSON study at 10 years of follow up among men, the cumulative rate ratio for death from lung cancer was significantly lower (rate ratio [RR] = 0.76, 95% CI: 0.61 to 0.94; p = 0.01) among those in the screening group who underwent low dose CT as compared with the control group who underwent no screening (de Koning, 2020). Among the small subsample of women, the non-significant rate ratio was 0.67 (95% CI: 0.38 to 1.14) at 10 years of follow up for lung cancer mortality comparing the low dose CT group to the control group, though the rate ratios were statistically significant at 7, 8, and 9 years of follow up (at 7 years: rate ratio = 0.46; 95% CI: 0.21  0.96; de Koning, 2020). There were no stratified analyses of lung cancer mortality by number of pack-years smoked as a subgroup that were shown in the NELSON study results. The authors concluded that in this trial involving high-risk persons, lung cancer mortality was significantly lower among those who underwent volume CT screening than among those who underwent no screening (de Koning, 2020). Additionally, the eligibility criterion for smoking history permitted persons who smoked 20 to 29 pack-years to be included in the NELSON study.Because the NELSON study showed a statistically significantly lower lung cancer death rate among men of all ages who underwent low dose CT and included persons who smoked 20 to 29 pack-years of cigarettes, the NELSON study provides convincing evidence for the discussion of lowering the smoking history eligibility criterion.Other small European studies, such as the LUSI and ITALUNG studies, had data on smokers with a 20 to 29 pack-year smoking history, but had differing results on lung cancer mortality. In the LUSI study, current smokers were described as long-term smokers but the study authors did not define long-term smokers (Becker, 2020). Eligibility for the LUSI study by smoking history criterion was defined by at least 25 years of smoking of at least 15 cigarettes per day, which is equivalent to at least 19 pack-years; or at least 30 years smoking of at least 10 cigarettes per day, which is at least equivalent to 15 pack-years (Becker, 2020). In the low dose CT intervention arm of the LUSI study, 50.2% were current smokers and 49.8% were ex-smokers (Becker, 2020). No definition of current smoker or ex-smoker was given in the study results. There were no data presented on the distribution of smoking history by subgroup of the number of pack-years smoked for the study population in the LUSI study results.Over an average observation time of 8.8 years after randomization, modeling by sex, however, showed a statistically significant reduction in lung cancer mortality among women (HR [hazard ratio] = 0.31 [95% CI: 0.10-0.96], p = 0.04), but not among men (HR = 0.94 [95% CI: 0.54-1.61], p = 0.81) screened by LDCT.. and this heterogeneity was close to statistical significance ([Pheterogeneity = 0.09) (Becker, 2020). There were no stratified analyses by smoking history for number of pack-years of smoking for lung cancer mortality in the LUSI study results. Because the smoking history eligibility criterion was defined as having at least 15 or 19 pack-years of smoking, it appears that the study population for the LUSI trial is likely to include smokers with a 20 to 25 pack-year smoking history. Thus, the LUSI study showed that low dose CT screening among persons with a 20 to 29 pack-year history reduces lung cancer mortality, especially among women.