In the LDCT group, 649 cancers were diagnosed after a positive screening test, 44 after a negative screening test, and 367 among participants who either missed the screening or received the diagnosis after the completion of the screening phase. In the radiography group, 279 cancers were diagnosed after a positive screening test, 137 after a negative screening test, and 525 among participants who either missed the screening or received the diagnosis after the completion of the screening phase. A total of 356 and 443 deaths from lung cancer occurred in the LDCT and chest x-ray groups, respectively, with a relative reduction in the rate of death from lung cancer of 20.0% (95% CI, 6.8–26.7) with LDCT screening. Overall mortality was reduced by 6.7% (95% CI, 1.2–13.6). The number needed to screen with low-dose CT to prevent one death from lung cancer was 320.
Other randomized controlled trials of LDCT are under way in a number of countries. Furthermore, NLST data are being analyzed to examine other important issues in lung cancer screening, including cost effectiveness, quality of life, and whether screening would benefit individuals younger than those enrolled in NLST and those with fewer than 30 pack-years of smoking exposure.
A Guide has been developed to help patients and physicians assess the benefits and harms of LDCT screening for lung cancer.
Evidence of no benefit associated with screening
Screening by chest x-ray and/or sputum cytology
The question of lung cancer screening dates back to the 1950s. Five studies of chest imaging, two of which were controlled, were undertaken during the 1950s and 1960s.[31,32,33,34,35,36,37,38] Two included sputum cytology as well.[31,32,33,34,35] The results of these studies suggested no overall benefit of screening, although design limitations prevented the studies from providing definitive evidence.
In the early 1970s, the National Cancer Institute funded the Cooperative Early Lung Cancer Detection Program, which was designed to assess the ability of screening with radiologic chest imaging and sputum cytology to reduce lung cancer mortality in male smokers. The program comprised three separate randomized controlled trials, each enrolling about 10,000 male participants aged 45 years and older who smoked at least one pack of cigarettes a day in the previous year. One study was conducted at the Mayo Clinic,[40,41,42] one at Johns Hopkins University,[43,44,45] and one at Memorial Sloan-Kettering.[45,46,47,48] The Hopkins and Sloan-Kettering studies employed the same design: persons randomly assigned to the intervention arm received sputum cytology every 4 months and annual chest imaging, while persons randomly assigned to the control arm received annual chest imaging. Neither study observed a reduction in lung cancer mortality with screening. The two studies were interpreted as showing no benefit of frequent sputum cytology when added to an annual regimen of chest x-ray.