A Systematic Review and Lessons Learned from Early Lung Cancer Detection Trials Using Low-Dose Computed Tomography of the Chest

Abstract

Computed tomography (CT) screening of the chest has shown promise for early detection of lung cancer, but evidence for a reduction in lung cancer mortality by CT screening is not available. We reviewed 208 articles to synthesize available evidence for efficacy of CT screening in detecting potentially curative stages of lung cancer and for evidence in reducing lung cancer mortality. Other outcomes of interest included detection rate of cancer and of suspicious lesions, histology and stage of cancer at detection, screening-related morbidity, and the identification of populations uniquely suited for CT screening. We identified eight papers that reported the outcomes for CT of the chest in lung cancer screening. Since none of the studies utilized a control group, quantitative pooling was not done. In two studies, both CT and chest radiography (CXR) were used as screening tools in the same cohorts. A total of 19,107 subjects were screened using CT. The detected prevalence rate for lung cancer ranged from 0.40% to 13.6% and was a function of the subjects' age and smoking history. CT screening resulted in a 3-fold higher detection rate and a 5-fold increase in the rate of resectable cancers compared to CXR. Data on lung cancer and overall mortality and screening-related morbidity and mortality were incomplete. CT screening resulted in selective detection of adenocarcinomas with an approximately 2- to 3-fold oversampling of this histologic subtype. The positive predictive value of CT screening was highest for subjects in the 8th decade of life, and it was virtually nil for those in their 5th decade. Evidence regarding lung cancer screening by CT shows that this technology detects earlier-stage and smaller lung cancers with greater frequency than other screening methods. To date, no trials have demonstrated that CT screening leads to a reduction in lung cancer mortality. Until mortality trials are completed, low-dose CT screening should be considered an investigative tool rather than the standard of care.