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

Author/s: 
Ebell, M.H., Bentivegna, M., Hulme, C.

Abstract

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.

Keywords: cancer screening; health services; low-dose computed tomography; lung cancer; mass screening; overdiagnosis; preventive medicine; public health.

© 2020 Annals of Family Medicine, Inc.

Keywords 
cancer screening health services low-dose computed tomography lung cancer mass screening overdiagnosis preventive medicine public health

Lung Cancer Screening with Low-Dose CT: a Meta-Analysis

Author/s: 
Hoffman, Richard M., Atallah, Rami P., Struble, Roger D., Badgett, Robert G

Background: Randomized controlled trials have evaluated the efficacy of low-dose CT (LDCT) lung cancer screening on lung cancer (LC) outcomes.

Objective: Meta-analyze LDCT lung cancer screening trials.

Methods: We identified studies by searching PubMed, Google Scholar, the Cochrane Registry, ClinicalTrials.gov , and reference lists from retrieved publications. We abstracted data on study design features, stage I LC diagnoses, LC and overall mortality, false positive results, harm from invasive diagnostic procedures, overdiagnosis, and significant incidental findings. We assessed study quality using the Cochrane risk-of-bias tool. We used random-effects models to calculate relative risks and assessed effect modulators with subgroup analyses and meta-regression.

Results: We identified 9 studies that enrolled 96,559 subjects. The risk of bias across studies was judged to be low. Overall, LDCT screening significantly increased the detection of stage I LC, RR = 2.93 (95% CI, 2.16-3.98), I2 = 19%, and reduced LC mortality, RR = 0.84 (95% CI, 0.75-0.93), I2 = 0%. The number needed to screen to prevent an LC death was 265. Women had a lower risk of LC death (RR = 0.69, 95% CI, 0.40-1.21) than men (RR = 0.86, 95% CI, 0.66-1.13), p value for interaction = 0.11. LDCT screening did not reduce overall mortality, RR = 0.96 (95% CI, 0.91-1.01), I2 = 0%. The pooled false positive rate was 8% (95% CI, 4-18); subjects with false positive results had < 1 in 1000 risk of major complications following invasive diagnostic procedures. The most valid estimates for overdiagnosis and significant incidental findings were 8.9% and 7.5%, respectively.

Discussion: LDCT screening significantly reduced LC mortality, though not overall mortality, with women appearing to benefit more than men. The estimated risks for false positive results, screening complications, overdiagnosis, and incidental findings were low. Long-term survival data were available only for North American and European studies limiting generalizability.

Keywords 
low-dose computed tomography lung cancer screening lung neoplasms meta-analysis mortality
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