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.
The design of the Mayo Clinic study (known as the Mayo Lung Project, or MLP), was different. All potential participants were screened with chest imaging and sputum cytology, and those known or suspected to have lung cancer, as well as those in poor health, were excluded. Remaining persons were randomly assigned to either an intervention arm that received chest imaging and sputum cytology every 4 months for 6 years, or to a control arm that received a one-time recommendation at trial entry to receive the same tests on an annual basis. No reduction in lung cancer mortality was observed. The MLP was interpreted in the 1970s as showing no benefit of an intense screening regimen with chest x-ray and sputum cytology. The Czechoslovakian study began with a prevalence screen (chest imaging and sputum cytology) of 6,364 males aged 40 to 64 years who were current smokers with a lifetime consumption of at least 150,000 cigarettes.[49,50] All participants except the 18 diagnosed with lung cancer as a result of the prevalence screen were randomly assigned to one of two arms: an intervention arm, which received semi-annual screening for 3 years, or a control arm, which received screening during the third year only. The investigators reported 19 lung cancer deaths in the intervention arm and 13 in the control arm, and concluded that frequent screening was not necessary.