Computed tomography screening for lung cancer: has it finally arrived? Implications of the national lung screening trial

Abstract

The National Lung Screening Trial (NLST) has provided compelling evidence of the efficacy of lung cancer screening using low-dose helical computed tomography (LDCT) to reduce lung cancer mortality. The NLST randomized 53,454 older current or former heavy smokers to receive LDCT or chest radiography (CXR) for three annual screens. Participants were observed for a median of 6.5 years for outcomes. Vital status was available in more than 95% of participants. LDCT was positive in 24.2% of screens, compared with 6.9% of CXRs; more than 95% of all positive LDCT screens were not associated with lung cancer. LDCT detected more than twice the number of early-stage lung cancers and resulted in a stage shift from advanced to early-stage disease. Complications of LDCT screening were minimal. Lung cancer-specific mortality was reduced by 20% relative to CXR; all-cause mortality was reduced by 6.7%. The major harms of LDCT are radiation exposure, high false-positive rates, and the potential for overdiagnosis. This review discusses the risks and benefits of LDCT screening as well as an approach to LDCT implementation that incorporates systematic screening practice with smoking cessation programs and offers opportunities for better determination of appropriate risk cohorts for screening and for better diagnostic prediction of lung cancer in the setting of screen-detected nodules. The challenges of implementation are considered for screening programs, for primary care clinicians, and across socioeconomic strata. Considerations for future research to complement imaging-based screening to reduce the burden of lung cancer are discussed.

Fig 1.

National Lung Screening Trial design. The trial was launched in August 2002. Over 20 months, 53,454 individuals were randomly assigned to receive either low-dose computed tomography (LDCT) or chest x-ray (CXR) for three annual screens. Outcomes through December 31, 2009, were collected on participants, an average of 6.5 years.

Fig 2.

Stage of lung cancers in the two screening arms based on result of screening. Lung cancers are shown as early-stage IA, intermediate-stage IB to IIB, and late-stage III to IV. In each arm, the stages are displayed by screen result, in which lung cancers were diagnosed after a positive screen, after a negative screen, or in participants who received no screen. Ninety percent of lung cancer diagnoses occurring with no screen occurred in the postscreening surveillance period. Lung cancers of unknown stage (n = 32) are excluded.

Fig 3.

Evolution of a ground-glass nodule to invasive adenocarcinoma. (A) Initial axial high-resolution computed tomography (CT) shows a 6-mm ground-glass nodule in the right lower lobe. (B) Follow-up high-resolution CT after 2.5 years shows a slight increase in size of the ground-glass nodule. (C) Final high-resolution CT at 8 years from initial detection demonstrates evolution of the nodule to an 8-mm solid nodule. At biopsy, this was an invasive adenocarcinoma.

Fig A1.

The original guidelines for the management of computed tomography (CT) –detected nodules in the National Lung Screening Trial. These guidelines were not mandated and could be used at the discretion of the interpreting radiologist. (*) Pure ground-glass nodules < 10 mm can be followed with low-dose helical CT (LDCT) at 6 to 12 months. At the final screen (T2), new nodules < 4 mm can be followed up at the discretion of the radiologist. (†) With lesions > 10 mm in diameter, institutional resources and preferences vary. (‡) The timing of repeat LDCT varies according to nodule size; larger nodules are followed up sooner than small nodules. (§) No growth is defined as < 15% increase in largest diameter or, with part-solid nodules, no increase in solid component. DCE-CT, dynamic contrast-enhanced computed tomography; FDG-PET, 18-fluorodeoxyglucose positron emission tomography; HU, Hounsfield unit.