The National Lung Screening Trial found that 3 years of annual screening with low-dose helical computed tomography (CT) reduced lung cancer mortality compared with chest radiography in older persons who were heavy smokers.¹ The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial also recently showed that mortality from lung cancer did not differ between subjects screened with radiography and those receiving usual care,² supporting earlier findings with chest radiography screening. In a report in The New England Journal of Medicine, the National Lung Screening Trial Research Team described the screening, diagnosis, and limited treatment results from the initial round of screening in the National Lung Screening Trial.³

Study Design

In the trial, 52,344 participants aged 55 to 74 years with a history of at least 30 pack-years of smoking (either current smokers or smokers within the prior 15 years) underwent annual screening for 3 years with low-dose CT (n = 26,309) or chest radiography (n = 26,305). These subjects accounted for 98.5% and 97.4%, respectively, of subjects initially randomized. Compliance with screening did not differ between the two groups according to age, sex, race/ethnic group, smoking status, or educational level.

For low-dose CT, all noncalcified nodules with long-axis diameters of 4 mm or greater in the axial plane were considered to be positive for potential lung cancer. For radiography, all noncalcified nodules and masses were considered to be positive. Screening results were classified as positive, negative with clinically significant abnormalities, negative with minor abnormalities, or negative with no abnormalities.

Major Findings

Positive screening results were found in 7,191 CT subjects (27.3%) and in 2,387 radiography subjects (9.2%). Rates of positivity increased slightly with increasing age and increasing number of pack-years in both groups. Negative results with clinically significant abnormalities were found in 2,695 CT subjects (10.2%) and in 785 radiography subjects (3.0%).

During follow-up, lung cancer was diagnosed in 292 subjects in the CT group (1.1%) and in 190 in the radiography group (0.7%). In the CT group, 270 subjects (92.5%) had a true-positive screening result, 18 (6.2%) had a false-negative screening result, and 4 (1.4%) missed the screening visit. Sensitivity and specificity values for CT were 93.8% and 73.4%, respectively. In the radiography group, 136 subjects (71.6%) had a true-positive screening result, 49 (25.8%) had a false-negative result, and 5 (2.6%) missed the screening visit. Sensitivity and specificity values for radiography were 73.5% and 91.3%, respectively.

In the CT group, the positive predictive value for positive findings leading to a biopsy was 52.9% but the overall positive predictive value for all positive findings was only 3.8%. Positive predictive values were 3.8% for nodules of 4 mm and increased to 41.3% for those with a diameter of more than 30 mm. The positive predictive value for noncalcified hilar or mediastinal adenopathy was 18.5%. Overall, the negative predictive value was 99.9%.

In the radiography group, positive predictive values were 70.2% for a positive finding that led to a biopsy procedure, but only 5.7% for all positive screening findings. Positive predictive values were 5.8% for pulmonary nodules and increased from 1.0% to 39.3% as diameter increased from 4 to 6 mm to more than 30 mm. The positive predictive value for noncalcified hilar or mediastinal adenopathy was 9.3%. Overall, the negative predictive value was 99.8%.

Diagnostic Procedures

At least one diagnostic procedure was performed in 6,369 (90.4%) of CT group subjects and 2,176 (92.7%) of radiography group subjects with positive screening findings. For the CT group and the radiography group, CT was performed in 5,153 (73.1%) and 1,546 (65.8%) subjects, FDG–positron-emission tomography was performed in 728 (10.3%) and 179 (7.6%), 155 (2.2%) and 83 (3.5%) underwent percutaneous cytologic or biopsy procedures, 306 (4.3%) and 107 (4.6%) underwent bronchoscopy, and 297 (4.2%) and 121 (5.2%) underwent a diagnostic surgical procedure. Overall, 10,313 imaging procedures, including 7,288 CT examinations, were performed in the CT group, compared with 3,657 imaging procedures, including 2,158 CT examinations, in the radiography group.

The difference between the CT group and the radiography group in number of diagnosed cancers was almost completely accounted for by a greater number of stage IA cancers diagnosed in the CT group (132 vs 46). There were no major differences in the numbers of stage IB (26 and 24), IIA (10 and 3), IIB (12 and 10), IIIA (34 and 29), IIIB (30 and 27), or IV (44 and 46) cancers diagnosed in the two groups.

More bronchioloalveolar carcinomas (38 and 8) and adenocarcinomas (123 and 71) were diagnosed in the CT group. A total of 277 CT group and 181 radiography group subjects were treated with some combination of surgery, chemotherapy, and radiotherapy, with 117 CT subjects and 40 radiography subjects with stage IA disease receiving surgery alone.

The investigators noted, “As expected, more positive screening results, more diagnostic procedures, more biopsies and other invasive procedures, and more lung cancers were seen in the low-dose CT group than in the radiography group during the first screening round. In addition, more early-stage lung cancers, but similar numbers of late-stage cancers, were diagnosed in the low-dose CT group.”

The investigators concluded, “The National Lung Screening Trial initial screening results are consistent with the existing literature on screening by means of low-dose CT and chest radiography, suggesting that a reduction in mortality from lung cancers is achievable at U.S. screening centers that have staff experienced in chest CT.” ■

Disclosure: For full disclosures of the study authors, visit www.nejm.org.

References

1. Aberle DR, Adams AM, Berg CD, et al: Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 365:395-409, 2011.

2. Oken MM, Hocking WG, Kvale PA, et al: Screening by chest radiograph and lung cancer mortality: The Prostate, Lung, Colorectal and Ovarian (PLCO) randomized trial. JAMA 306:1865-1873, 2011.

3. The National Lung Screening Trial Research Team: Results of initial low-dose computed tomographic screening for lung cancer. N Engl J Med 368:1980-1991, 2013.