Cancer-Specific Mortality, All-Cause Mortality, and Overdiagnosis in Lung Cancer Screening Trials: A Meta-Analysis

Purpose: Benefit of lung cancer screening using low-dose computed tomography (LDCT) in reducing lung cancer-specific and all-cause mortality is unclear. We undertook a meta-analysis to assess its associations with outcomes.

Methods: We searched the literature and previous systematic reviews to identify randomized controlled trials comparing LDCT screening with usual care or chest radiography. We performed meta-analysis using a random effects model. The primary outcomes were lung cancer-specific mortality, all-cause mortality, and the cumulative incidence ratio of lung cancer between screened and unscreened groups as a measure of overdiagnosis.

Results: Meta-analysis was based on 8 trials with 90,475 patients that had a low risk of bias. There was a significant reduction in lung cancer-specific mortality with LDCT screening (relative risk = 0.81; 95% CI, 0.74-0.89); the estimated absolute risk reduction was 0.4% (number needed to screen = 250). The reduction in all-cause mortality was not statistically significant (relative risk = 0.96; 95% CI, 0.92-1.01), but the absolute reduction was consistent with that for lung cancer-specific mortality (0.34%; number needed to screen = 294). In the studies with the longest duration of follow-up, the incidence of lung cancer was 25% higher in the screened group, corresponding to a 20% rate of overdiagnosis.

Conclusions: This meta-analysis showing a significant reduction in lung cancer-specific mortality, albeit with a tradeoff of likely overdiagnosis, supports recommendations to screen individuals at elevated risk for lung cancer with LDCT.