Lung cancer is the primary cause of cancer mortality in developed countries. First diagnosis only when disease has already reached the metastatic phase is the main reason for failure in treatment. To this regard, although low-dose spiral computed tomography (CT) has proven to be effective in the early detection of lung cancer (providing both higher resectability and higher long-term survival rates), the capacity of annual CT screening to reduce lung cancer mortality in heavy smokers has yet to be demonstrated. Numerous ongoing large-scale randomised trials are under way in high-risk individuals with different study designs.
THE MAGNITUDE OF THE PROBLEMLung cancer kills more than 1.3 million people every year (Peto et al, 1996), with figures registering a continual increase in the Far East in countries such as China (Yang et al, 2004). Improvements in clinical management have been modest over the past 20 years, with an overall 5-year survival rate just above 10% in Europe (Verdecchia et al, 2007). Presence of metastatic disease at diagnosis is the main reason for treatment failure, and 5-year survival of patients resected in stage Ia is 470% (Goldstraw et al, 2007). In developed countries, smoking sanctions have achieved a significant reduction in the prevalence of active smokers and lung cancer mortality in males, but not yet in females (Levi et al, 2003). Despite the success of early prevention, a large cohort of former smokers remain at high risk of cancer for many years.
PREVIOUS RESEARCH INVOLVING OTHER MODALITIESEarly detection trials with chest radiography (CXR) and sputum cytology, funded by the US National Cancer Institute in the 1970s, were ineffective in decreasing lung cancer mortality, despite the higher proportion of early-stage cancer identified through screening (Melamed et al, 1984). Quite unexpectedly, the 25-year followup of the Mayo trial showed that overall mortality was higher in the CXR arm compared with the standard care arm (difference not reaching statistical significance, P ¼ 0.09), even though the survival rate of lung cancer patients diagnosed at an early stage in the CXR arm was much higher (69 vs 54% at 5 years, median 16 years vs 5 years, respectively) (Marcus et al, 2006). These results confirmed the inefficacy of CXR monitoring, as well as the occurrence of overdiagnosis in the intervention arm.
OBSERVATIONAL STUDIES WITH LOW-DOSE SPIRAL CTThe advent of low-dose spiral chest computed tomography (LDCT) opened a new perspective for early diagnosis, and initial studies conducted in Japan in the 1990s demonstrated the potential value of LDCT for lung cancer screening (Kaneko et al, 1996). Since then, the rapid technological development in multislice machines has improved the sensitivity and reliability of spiral CT, providing the concrete possibility of detecting pulmonary lesions of 3 -4 mm in size in a few seconds, without the use of intravenous contrast.In 1999, the Cornell University of New York published the first results of the Early Lung Cancer Action Project (ELCAP), showing...