Benefits and harms of computed tomography lung cancer screening strategies: a comparative modeling study for the U.S. Preventive Services Task Force

Abstract

Background: The optimum screening policy for lung cancer is unknown.

Objective: To identify efficient computed tomography (CT) screening scenarios in which relatively more lung cancer deaths are averted for fewer CT screening examinations.

Design: Comparative modeling study using 5 independent models.

Data sources: The National Lung Screening Trial; the Prostate, Lung, Colorectal, and Ovarian Cancer Screening trial; the Surveillance, Epidemiology, and End Results program; and the U.S. Smoking History Generator.

Target population: U.S. cohort born in 1950.

Time horizon: Cohort followed from ages 45 to 90 years.

Perspective: Societal.

Intervention: 576 scenarios with varying eligibility criteria (age, pack-years of smoking, years since quitting) and screening intervals.

Outcome measures: Benefits included lung cancer deaths averted or life-years gained. Harms included CT examinations, false-positive results (including those obtained from biopsy/surgery), overdiagnosed cases, and radiation-related deaths.

Results of best-case scenario: The most advantageous strategy was annual screening from ages 55 through 80 years for ever-smokers with a smoking history of at least 30 pack-years and ex-smokers with less than 15 years since quitting. It would lead to 50% (model ranges, 45% to 54%) of cases of cancer being detected at an early stage (stage I/II), 575 screening examinations per lung cancer death averted, a 14% (range, 8.2% to 23.5%) reduction in lung cancer mortality, 497 lung cancer deaths averted, and 5250 life-years gained per the 100,000-member cohort. Harms would include 67,550 false-positive test results, 910 biopsies or surgeries for benign lesions, and 190 overdiagnosed cases of cancer (3.7% of all cases of lung cancer [model ranges, 1.4% to 8.3%]).

Results of sensitivity analysis: The number of cancer deaths averted for the scenario varied across models between 177 and 862; the number of overdiagnosed cases of cancer varied between 72 and 426.

Limitations: Scenarios assumed 100% screening adherence. Data derived from trials with short duration were extrapolated to lifetime follow-up.

Conclusion: Annual CT screening for lung cancer has a favorable benefit-harm ratio for individuals aged 55 through 80 years with 30 or more pack-years' exposure to smoking.

Primary funding source: National Cancer Institute.

Figure 1

Estimated lung cancer mortality reduction (as percentage of total lung cancer mortality in cohort) and life-years gained (averages of 5 models) from annual (A) CT screening, for programs with minimum eligibility age 55 and maximum at 80 at different smoking eligibility cutoffs and NLST scenario (A-55-75-30-15). Average number of CT screens (5 models) on X-axis. The graph plots the average number of CT screens against the percentage of lung cancer mortality reduction for each screening scenario (vs.no screening) that was estimated for 100,000 individuals of the 1950-cohort followed from age 45 to 90. Programs are labeled: Frequency-Start Age-Stop Age-minimum Pack Years-maximum Years Since Quit. The lung cancer mortality reductions are different from the point estimate of the reduction reported at the 6.5 year follow-up in the NLST, since only eligible persons get screened in this cohort analysis (dilution) and life-time lung cancer mortality reduction is modeled. The panel shows the efficiency frontier for all models combined. When the slope in the efficiency frontier plot levels off, the additional reductions in mortality per unit increase in use of CT screens are small relative to the previous strategies.

Figure 2

Estimated percentage lung cancer mortality reduction and overdiagnosed cases (of screen-detected cases) for the highlighted scenarios in Tables 1 and 2 (average number of CT-screens on X-axis) for all individual models and the average of the 5 models. Presentation of a 100,000 1950-cohort followed from age 45 to 90.

Figure 2

Estimated percentage lung cancer mortality reduction and overdiagnosed cases (of screen-detected cases) for the highlighted scenarios in Tables 1 and 2 (average number of CT-screens on X-axis) for all individual models and the average of the 5 models. Presentation of a 100,000 1950-cohort followed from age 45 to 90.