Lung Cancer Incidence and Mortality with Extended Follow-up in the National Lung Screening Trial

Abstract

Introduction: The National Lung Screening Trial (NLST) randomized high-risk current and former smokers to three annual screens with either low-dose computed tomography (LDCT) or chest radiography (CXR) and demonstrated a significant reduction in lung cancer mortality in the LDCT arm after a median of 6.5 years' follow-up. We report on extended follow-up of NLST subjects.

Methods: Subjects were followed by linkage to state cancer registries and the National Death Index. The number needed to screen (NNS) to prevent one lung cancer death was computed as the reciprocal of the difference in the proportion of patients dying of lung cancer across arms. Lung cancer mortality rate ratios (RRs) were computed overall and adjusted for dilution effect, with the latter including only deaths with a corresponding diagnosis close enough to the end of protocol screening.

Results: The median follow-up times were 11.3 years for incidence and 12.3 years for mortality. In all, 1701 and 1681 lung cancers were diagnosed in the LDCT and CXR arms, respectively (RR = 1.01, 95% confidence interval [CI]: 0.95-1.09). The observed numbers of lung cancer deaths were 1147 (with LDCT) versus 1236 (with CXR) (RR = 0.92, 95% CI: 0.85-1.00). The difference in the number of patients dying of lung cancer (per 1000) across arms was 3.3, translating into an NNS of 303, which is similar to the original NNS estimate of around 320. The dilution-adjusted lung cancer mortality RR was 0.89 (95% CI: 0.80-0.997). With regard to overall mortality, there were 5253 (with LDCT) and 5366 (with CXR) deaths, for a difference across arms (per 1000) of 4.2 (95% CI: -2.6 to 10.9).

Conclusion: Extended follow-up of the NLST showed an NNS similar to that of the original analysis. There was no overall increase in lung cancer incidence in the LDCT arm versus in the CXR arm.

Keywords: Incidence; Low-dose CT; Lung cancer; Mortality; Screening.

Figure 1.

Cumulative lung cancer cases by arm. A) All lung cancers. Black is LDCT arm, red is CXR arm. Gray line represents excess of cases in the LDCT arm over the CXR arm. B) All cases excluding bronchioloalveolar carcinoma (BAC) are solid lines, BAC cases are dotted lines. Black is LDCT arm, red is CXR arm.

Figure 1.

Cumulative lung cancer cases by arm. A) All lung cancers. Black is LDCT arm, red is CXR arm. Gray line represents excess of cases in the LDCT arm over the CXR arm. B) All cases excluding bronchioloalveolar carcinoma (BAC) are solid lines, BAC cases are dotted lines. Black is LDCT arm, red is CXR arm.

Figure 2.

A. Lung cancer deaths by trial arm. Black is LDCT arm, red is CXR arm; solid lines are all deaths and dotted lines show deaths for the dilution-adjusted analysis. Vertical bars show number of deaths for each study year. Black/gray and red/purple bars are for CXR and LDCT arms, respectively. Total height is all deaths, height of black/red segment shows number of deaths for dilution-adjusted analysis. B. Stage IV lung cancers cases by trial arm. Black is LDCT arm, red is CXR arm.

Figure 2.

A. Lung cancer deaths by trial arm. Black is LDCT arm, red is CXR arm; solid lines are all deaths and dotted lines show deaths for the dilution-adjusted analysis. Vertical bars show number of deaths for each study year. Black/gray and red/purple bars are for CXR and LDCT arms, respectively. Total height is all deaths, height of black/red segment shows number of deaths for dilution-adjusted analysis. B. Stage IV lung cancers cases by trial arm. Black is LDCT arm, red is CXR arm.