Lung cancer is the cause of more than one-fifth of all cancer deaths in many developed countries. Although the main risk factor – smoking – has declined in these countries in recent decades, many millions of people are still at risk from this devastating disease. It is particularly intractable because of its complex, heterogeneous and often aggressive nature, leading to late diagnoses. Several trials of screening with high-risk groups, using chest radiography with or without sputum analysis, have shown no effect on lung cancer mortality.

More recently, however, multi-detector computed tomography (CT) has developed to a level that has enabled high resolution volumetric images to be obtained in a single breath-hold. Observational evidence suggests that this is enabling lung tumours to be detected at an earlier and more tractable stage. The National Lung Screening Trial (NLST) was established in the USA in 2002 with funding from the National Cancer Institute to test whether this type of screening was statistically superior to chest radiography in reducing deaths from lung cancer in high risk groups. The NLST Research Team, led by Christine

D. Berg from the National Cancer Institute's Division of Cancer Prevention, Bethesda, Maryland, USA has now published the results of this trial.

A total of 53,454 subjects were enrolled in the trial between 2002 and 2004. All were current or former smokers who were between the ages of 55 and 74 when enrolled and who were considered at high risk of developing lung cancer. The demographic characteristics of the two groups were almost identical, with 59% of each group being male. Half were randomised to receive screening by low-dose CT and half by chest radiography, both groups using standard protocols; both groups were screened three times, first soon after randomisation and then at two yearly intervals. All participants were followed up until December 2009. Suspicious lesions were noted along with minor abnormalities, and tissue samples were obtained from diagnosed lung cancers and other lesions. The primary analysis was a comparison of rates of death from lung cancer between the groups, with diagnosed cases of lung cancer and death from any cause as secondary analyses.

Approximately 95% of the participants in the CT screening group and 93% of those in the radiography group adhered to their assigned screening program. Both positive results and results showing abnormalities not suspicious for lung cancer were detected more often in the CT screening group than in the radiography group (24.2% versus 6.9% for positive results, and 7.5% versus 2.1% for other significant abnormalities, averaged over all three screens). However, a larger number of the positive results from CT screening were classed as false positives. There were few significant adverse events from either procedure.

Lung cancer was diagnosed more often in the low-dose CT group (1060 cancers, or 645 per 100,000 person-years) than in the radiography group (941 cancers, or 572 per person-years. However, the position was reversed for mortality, with 247 deaths per 100,000 person-years in the CT group and 309 in the radiography group. This represents a relative reduction in lung cancer deaths of 20.0% in the CT group (95% CI, 6.8 to 26.7; P = 0.004). There was also a smaller but statistically significant reduction of 6.7% in deaths from all causes in the CT group 6.7% (95% CI, 1.2 to 13.6; P = 0.02). The main reason for this reduction was that more early-stage cancers were detected with CT than with radiography.

The adverse event profile and data on death from all causes indicates that CT tomography is safe, and its already superior capacity to detect lung cancer at a treatable stage is likely to improve with advances in CT technology. However, the high number of false positive results – with implications for cost-effectiveness as well as for the distress caused by false cancer diagnoses – must be taken into account in determining the extent to which it should be used in the clinic.

Reference

The National Lung Screening Trial Research Team[1] (2011). Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening, N. Engl. J. Med., published online ahead of print June 29, 2011. DOI: 10.1056/NEJMoa1102873

[1] Writing team of 10 led by Berg, C.D.