Targeting of low-dose CT screening according to the risk of lung-cancer death

Abstract

Background: In the National Lung Screening Trial (NLST), screening with low-dose computed tomography (CT) resulted in a 20% reduction in lung-cancer mortality among participants between the ages of 55 and 74 years with a minimum of 30 pack-years of smoking and no more than 15 years since quitting. It is not known whether the benefits and potential harms of such screening vary according to lung-cancer risk.

Methods: We assessed the variation in efficacy, the number of false positive results, and the number of lung-cancer deaths prevented among 26,604 participants in the NLST who underwent low-dose CT screening, as compared with the 26,554 participants who underwent chest radiography, according to the quintile of 5-year risk of lung-cancer death (ranging from 0.15 to 0.55% in the lowest-risk group [quintile 1] to more than 2.00% in the highest-risk group [quintile 5]).

Results: The number of lung-cancer deaths per 10,000 person-years that were prevented in the CT-screening group, as compared with the radiography group, increased according to risk quintile (0.2 in quintile 1, 3.5 in quintile 2, 5.1 in quintile 3, 11.0 in quintile 4, and 12.0 in quintile 5; P=0.01 for trend). Across risk quintiles, there were significant decreasing trends in the number of participants with false positive results per screening-prevented lung-cancer death (1648 in quintile 1, 181 in quintile 2, 147 in quintile 3, 64 in quintile 4, and 65 in quintile 5). The 60% of participants at highest risk for lung-cancer death (quintiles 3 through 5) accounted for 88% of the screening-prevented lung-cancer deaths and for 64% of participants with false positive results. The 20% of participants at lowest risk (quintile 1) accounted for only 1% of prevented lung-cancer deaths.

Conclusions: Screening with low-dose CT prevented the greatest number of deaths from lung cancer among participants who were at highest risk and prevented very few deaths among those at lowest risk. These findings provide empirical support for risk-based targeting of smokers for such screening. (Funded by the National Cancer Institute.).

Figure 1. Efficacy of Low-Dose CT Screening, According to Risk Quintile

Panel A shows the lung-cancer mortality ratio for the low-dose CT group versus the radiography group among risk quintiles 1 through 5 (Q1 through Q5, each 20% of the screening group) for the prescreening 5-year risk of lung-cancer death. Panel B shows the number of lung-cancer deaths prevented by low-dose CT (i.e., the between-group difference) among the risk quintiles. The exact boundaries for the risk of 5-year lung-cancer death for each quintile, as percentages, are shown on the x axis. Bars denote 95% confidence intervals. The horizontal gray lines indicate the overall efficacy of low-dose CT screening. The gray symbols indicate the efficacy outcomes in risk quintiles as defined by four published prediction models of lung-cancer incidence: Bach et al., Spitz et al., Cassidy et al. (for the Liverpool Lung Project [LLP]), and Tammemagi et al.

Figure 2. Cumulative Screening Outcomes in the Low-Dose CT Group

Each panel shows cumulative screening outcomes in the low-dose CT group, from highest risk in quintile 5 (Q5, on the left) to overall risk in quintiles 1 through 5 (Q1–Q5, on the right). The risk cutoff defining each group and the represented number and proportion of patients are indicated below the x axis. Panel A shows the cumulative number of lung-cancer deaths that were prevented in the low-dose CT group, as compared with the radiography group, with the corresponding percentage over each bar. Panel B shows the number of participants who would need to undergo three annual screenings with low-dose CT to prevent one lung-cancer death. Panel C shows the cumulative number of participants with false positive results on screening, with the corresponding percentage over each bar. Panel D shows the cumulative number of participants with false positive results on screening per CT-prevented lung-cancer death.