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

Table 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)de Koning (2020) NELSON (RCT) Netherlands, Belgium (15,792 total; 13,195 men, 2594 women)50  to 74Median: males: 58 (IQR: 55-63)Range 46-7650-54: 24.6% (1611/6560)  75: 0.6% (40/6560)Not shown16.4%10 yr (actual)RR: 0.76 (0.61 - 0.94; P = 0.01)RR men 50-54: 0.85 (0.48 - 1.50)Doroudi (2018) LSS (RCT) United States (3,318)55 to 74No age data for study population shownNot shownNot shown5.2  yrRR:  1.24 (0.74 - 2.08)Field (May, 2016) UKLS (RCT) United Kingdom (4,055)50 to 7550-55: 0.7%71-75: 22.4%99% White1% non-white25.1%Not shownNo lung cancer mortality; Only lung cancer incidenceField (February, 2016) UKLS (RCT) United Kingdom (4,055)50 to 75Mean: 67.1  (SD 4.1)Median: 67 Range: 50 to 7599% White1% non-white25.1%1 yrLung cancer mortality not assessed; Confirmed lung cancerInfante (2015) DANTE (RCT) Italy (2,450 men)60 to 74Mean (95% CI): 64.6 (64.364.8)Median: 64.0 (IQR 5)Not shown0%8.35 yr (median)HR: 0.993 (0.691.43)Infante (Pooled, 2017) (pooled analysis DANTE and MILD) Italy (6,549) 49 to 74Median: 61 (IQR 10) 60:  48.5% (1766/3640)>60: 51.5% (1874/3640)Not shown21.5%8.2 yr (median)Pooled  HR: 0.83 (0.611.12)National Lung Screening Trial Research Team (2019) NLST (RCT) United States (53,452)55 to 7455-74: 42.8% (11442 / 26722)70-74: 8.8% (2354/26722)89.6%White4.4%Black1.7% Hispanic2.0%Asian0.3% AmericanIndian /NativeAlaskan0.3%NativeHawaiian/Pacific Islander1.6% Other /unknown41.0%12.3  yr (median)RR dilution-adjusted: 0.89 (0.800.997)Tanner (2016) NLST (secondary analysis of NLST) United States (53,452)55 to 74Not shown89.6% White4.4% Black6.0% Other /  Missing41.0%Not shownHR: 0.62 (0.510.76)Paci (2017) ITALUNG (RCT) Italy (3,206)55 to 69Mean: 60.9<55: 3% (53/1613)>69: 0.3%  (5/1613)Not  shown35.3%9.3 yrRR:  0.70 (0.47 - 1.03; p = 0.07)Paci (2021) ITALUNG (secondary analysis) Italy (3,206)55 to 69<55: 3% 70: 0%Not shown35%10  yr10 yr survival rates for lung cancer cases: 64% active arm vs 60% control arm (p = 0.69)Pastorino, Silva (Prolonged; July, 2019) MILD (RCT) Italy (4,099)49 to 75Median: 58< 55: 32.5% (773/2376) 70: 3.8% (90/2376)Not shown33.7%10 yrHR: 0.61 (0.39  0.95; p = 0.02)Pastorino, Sverzellati (Ten Year; September, 2019) MILD (secondary analysis of RCT) Italy  (2,376) (subset of screening arm)49 to 75<55: 32.5% (773/2376) 65: 15.5% (368/2376)Not shown31.6%10 yrBiennial (low dose CT every 24 months) arm compared to annual arm: HR: 1.10 (0.59 -2.05)Rampinelli (2017) COSMOS (secondary retrospective analysis of observational screening trial)  Italy (5,203)50 and older50-54: 33.8% (1759/5203) 65: 12% (658/5203)age range not shownNot shown33.9%10 yrNo lung cancer mortality, but lifetime attributable risk of cancer incidence and radiation exposure doseWille (2016) DLCST (RCT) Denmark (4,104)50 to 70Mean 57.9  4.8Not shown44.8%> 5 yrs after last screen, mean follow up duration not shownHR:  1.03 (0.66 1.6; p = 0.89)Table 2. Age Eligibility Criteria for Low Dose CT Observational Studies and Meta-AnalysesFirst Author, (year published) Study Acronym, Study DesignPopulation: Country Overall Sample Size (n)Age Inclusion Criteria (years)Age Distribution in Screening Study Population (mean; lowest and highest age groups; frequency;  n, years)Timing: Follow up Duration (mean, median; years)Outcome: Lung Cancer Mortality: Low Dose CT Arm Compared Control Arm (HR, RR, or OR, 95% CI; p value)Dement (2020) (prediction modeling)United States (17,069)Not shownNo age dataNot shownModeling resultsHoreweg (2014) NELSON (RCT)Netherlands, Belgium (7,155)50 to 75Median: 58.0 (IQR 54.0-62.0)Not shownNo lung cancer mortality; Results: sensitivity, specificity, positive predictive value; interval cancers, screen-detected lung cancerLeleu (2020) DEP KP80 (single arm prospective study)France (1,307)55 to 74Mean: 61.8Not shownNo lung cancer mortality; Results: prevalence of lung cancer 2.7%.Liang (2019) (cancer registry study)Shanghai and two districts, China (over 9.5 million)Inclusion criteria for age not shown35-3940-4445-4950-5470-7475-7980-8485no sample sizes shownNo follow up period notedLung cancer mortality rate as average annual percent change [APC] = -1.71%, 95% CI: -2.98% 0.04%, P= 0.015)Nawa (2019) (retrospective cohort study)Japan (210) 50Not shown4 to 8 years after introduction of CT screeningReduction (24%) in lung cancer mortalityPatz (2016) NLST (retrospective cohort subgroup analysis)United States (26,231, with negative T0 screen)55 to 74Negative T0 screen60 (55-74)6.4 yrNegative T0 screen vs all T0 screen: 185.8 (95% CI 162.2211.9) per 100,000 person-years vs 277.2 (252.3303.9)Rulli (2020) (retrospective review)United States (2,924)55 to 79No age specific data shown3 yrLung cancer mortality rate 239 per 100,000 patients.White (2020) (retrospective review)United States (962)Not shownNo age reportedNot shownLung cancer rateWhittaker Brown (2019) NLST (subgroup analysis of interstitial lung abnormalities)United States (50,206)55 to 74Median 61 (IQR 58-66)Not shownHR: 1.51 (1.13-2.03)Wu (2019) (retrospective cohort study)Asian population (2,883)Not shown59.91  8.14Not shownOverall  mortality of 10.75% in screened groupMeta-AnalysesHuang (2019) (9 RCTs)Italy, Denmark, Germany, US, Netherlands, Belgium, China (97,244)45-60 to 69-75Mean 57.9 -61.0  4.8-5.8Median 57.0-64.0 (IQR 5-8)Range 55-74HeterogeneousPooled RR: 0.83 (0.760.90, I2= 1%)Sadate (2020) (7 RCTs)Italy, Denmark, Germany, United States, Belgium, The Netherlands (84,558) 49-60 to 69-74Age data not shown for study population3-10 yrPooled RR: 0.83 (0.76-0.91; I2= 0%)Wang (2018) (4 RCTs)United States, Italy (2), Denmark, (64,129) 49-60 to 70-74Age data not shown for study populationMedian 33.7 months to 6.5 yr; 4.8 person-yearsPooled OR: 1.13 (0.781.64; I2> 75%)Yang (2019) (4 RCTs)United States, Italy (2), Denmark (64,468)>49-60 to 70-74Age data not shown for study populationHeterogeneous: 6 yr 3.5 months to 9.47 yrPooled RR: 0.94 (0.74-1.19; p = 0.62; I2= 43.3%)Table 3. Smoking History Eligibility Criteria for Low Dose CT Randomized Controlled Trials and Meta-AnalysesFirst Author, (year published) Study Acronym, Study DesignSmoking History Inclusion Criteria (pack-years)Smoking History Study Population Distribution in Intervention Arm (mean  SD; frequency, range, or percent; pack-years)Smoking Cessation Inclusion Criteria (years since quitting smoking)Smoking Cessation Duration Since Quitting: Distribution in Study Population Intervention Arm   (n, years since quitting)Timing: Follow up Duration (mean, median; years)Outcome: Lung Cancer Mortality: Low Dose CT Arm Compared Control Arm (HR, RR, or OR, 95% CI; p value)Becker (2020)  LUSI (RCT)At least 25 years smoking of at least 15 cigarettes per day, or at least 30 years smoking of at least 10 cigarettes per dayNo pack-years shownStopped smoking not more than 10 years before invitation to screeningNone shown8.8  yr (median)HR: 0.74 (0.46  1.19; p = 0.21) HR women: 0.31 (0.10 0.96, p = 0.04)