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Description of the Evidence

    continued...

    A study in Ireland,[17] 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,[18] noncalcified nodules were detected in 51% of 1,520 patients at the prevalence screen and cumulatively in 74% after five subsequent annual screens.[20] 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.

    In a 2008 systematic review of chest CT lung cancer screening studies, the mean proportion of patients with any incidental abnormality was 65.2% (95% confidence interval [CI], 63.5%–66.9%). The mean proportion of patients with clinically significant incidental findings—defined as any abnormality considered to require additional diagnostic workup—was 14.2% (95% CI, 13.2%–15.2%).[21] It is not clear whether the detection of these abnormalities produces a net benefit or a net harm.[18]

    A less familiar harm is overdiagnosis,[22] the diagnosis of a condition that would not have become clinically significant had it not been detected by screening. In the case of screening with LDCT, overdiagnosis could lead to unnecessary diagnosis of lung cancer requiring some combination of surgery (e.g., lobectomy), chemotherapy, and radiation therapy. Although overdiagnosis is almost impossible to document in a living individual, autopsy studies suggest that many individuals die with lung cancer rather than from it. In one study, about one-sixth of all lung cancers found at autopsy had not been clinically recognized before death.[23] Even this may be an underestimate because autopsy probably fails to detect many small lung cancers that are detectable by CT.[24] Studies in Japan provide additional evidence that screening with LDCT could lead to a substantial amount of overdiagnosis.[25] In a study in which smokers and nonsmokers were annually screened for lung cancer between 1996 and 1998 using LDCT, the overall rate of screen-detected lung cancers was very similar in the two groups: 0.46% for smokers (mainly men) and 0.41% for nonsmokers (mainly women).[26] The nonsmoking group may have included individuals who were at an elevated risk for lung cancers for other reasons, but no information is provided on this point. A second study involving both smokers and nonsmokers reported a similar finding of a 1.1% lung cancer detection rate in both groups.[27] Confirmative studies are needed to establish the level of overdiagnosis that might be associated with CT screening for lung cancer. In that same population, the volume-doubling times of 61 lung cancers were estimated using an exponential model and successive CT images. Lesions were classified into three types: (1) type G (ground glass opacity), (2) type GS (focal glass opacity with a solid central component), and (3) type S (solid nodule). The mean-doubling times were 813 days, 457 days, and 149 days for types G, GS, and S, respectively. In this study, annual CT screening identified a large number of slowly growing adenocarcinomas that were not visible on chest x-ray.[28]

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