Eight observational studies of LDCT in various parts of the world have been reported and summarized. These are relatively small studies, ranging from about 600 to 8,000 participants, which began between 1992 and 2000. Most of the studies include a substantial percentage of females, and the studies in Japan include nonsmokers. Findings include a nodule or positivity rate of 5% to 51%, 0.4% to 3% lung cancers, 50% to 95% adenocarcinomas, 50% to 91% stage I or IA cancers, and estimates of sensitivity ranging from 40% to 95%.
False-positive test results and overdiagnosis must be considered when lung cancer screening with LDCT is being evaluated. The false-positive test result, which is more common than overdiagnosis, may lead to anxiety and invasive diagnostic procedures such as percutaneous needle biopsy or thoracotomy. In the ELCAP study, which used a CT slice thickness of 10 mm, noncalcified nodules were detected in 21% of patients without lung cancer at the prevalence screen. Thirty-one (13%) of 233 individuals with noncalcified nodules underwent biopsies, of which close to 90% (27 of 31 patients) resulted in a diagnosis of malignancy, and the prevalence of cancers detected was 2.7%.
In a case series that defined the population at high risk of lung cancer by occupations associated with asbestos exposure, 58% accepted an invitation to participate in an LDCT screening program. The ELCAP screening protocol was applied in 1,119 asbestos-exposed people whose average age was 57 years. Twenty-five biopsies resulted in the detection of one stage IA and four late stage lung cancers. The authors concluded the screening program was not able to replicate the ELCAP results and was not cost effective for lung cancer screening in this population.
A study in Ireland, which aimed to reproduce the ELCAP study in high-risk but younger individuals, revealed a similar proportion of noncalcified nodules were detected using 10 mm CT slice thickness. In the Irish study (N = 449), however, the prevalence of cancers detected was substantially smaller (0.46%). Furthermore, several individuals underwent invasive procedures for ultimately benign conditions (three of four patients with nodules >10 mm who underwent biopsy had benign cytology; one had a thoracotomy that confirmed benign disease; three patients with mediastinal masses underwent biopsy and two had benign cysts). In two other studies, which used 5 mm CT slices, noncalcified nodules were detected in a much higher proportion of patients.[18,19]
In the Mayo Clinic study, noncalcified nodules were detected in 51% of 1,520 patients at the prevalence screen and cumulatively in 74% after five subsequent annual screens. Ninety-five percent of these nodules were less than 8 mm in diameter, for which the recommended follow-up was noncontrast CT in 3 to 6 months. However, eight patients had surgery for benign lesions, five of which appeared to grow on follow-up CT. In addition, screening with LDCT can detect abnormalities other than noncalcified nodules, including enlarged lymph nodes, abdominal aortic aneurysms, and renal and adrenal masses. During the first three rounds of screening in the Mayo Clinic study, 696 such abnormalities were found in the 1,520 patients.