Comparing benefits from many possible computed tomography lung cancer screening programs: extrapolating from the National Lung Screening Trial using comparative modeling

Abstract

Background: The National Lung Screening Trial (NLST) demonstrated that in current and former smokers aged 55 to 74 years, with at least 30 pack-years of cigarette smoking history and who had quit smoking no more than 15 years ago, 3 annual computed tomography (CT) screens reduced lung cancer-specific mortality by 20% relative to 3 annual chest X-ray screens. We compared the benefits achievable with 576 lung cancer screening programs that varied CT screen number and frequency, ages of screening, and eligibility based on smoking.

Methods and findings: We used five independent microsimulation models with lung cancer natural history parameters previously calibrated to the NLST to simulate life histories of the US cohort born in 1950 under all 576 programs. 'Efficient' (within model) programs prevented the greatest number of lung cancer deaths, compared to no screening, for a given number of CT screens. Among 120 'consensus efficient' (identified as efficient across models) programs, the average starting age was 55 years, the stopping age was 80 or 85 years, the average minimum pack-years was 27, and the maximum years since quitting was 20. Among consensus efficient programs, 11% to 40% of the cohort was screened, and 153 to 846 lung cancer deaths were averted per 100,000 people. In all models, annual screening based on age and smoking eligibility in NLST was not efficient; continuing screening to age 80 or 85 years was more efficient.

Conclusions: Consensus results from five models identified a set of efficient screening programs that include annual CT lung cancer screening using criteria like NLST eligibility but extended to older ages. Guidelines for screening should also consider harms of screening and individual patient characteristics.

Figure 1. Systematic variation of reference screening program A55-75-30-15.

Vertical axis normalized so that 1.0 represents within-model prediction of lung cancer deaths avoided with most intensive screening program (A45-85-10-25); values not directly interpretable as a hazard ratio. Compared to annual screening of individuals aged 55 to 74 with at least 30 pack-years of cigarette smoking and who quit with in the last 15 years (reference, x) a program of continuing annual screening to eligible individuals up to age 85 (+) was closer to the efficiency frontier. Results from one model shown; see Figure S7 in File S1 for results from all five models.

Figure 2. Exemplar model showing consensus programs.

Vertical axis normalized as in Figure 1. Consensus programs were the 120 (out of 576 evaluated, see Table 2) that five models ranked as most efficient. Only a single consenus strategy (the single orange +) had a stop age of 75. The remaining consensus strategies continued screening of individuals meeting the smoking eligibility criteria to ages 80 (aqua) or 85 (purple). Annual screening (triangles) provided greater benefits (i.e., averted more lung cancer deaths) than triennial (+) or biennial (squares). Results from one model shown; see Figure S8 in File S1 for results from all five models.

Figure 3. Normalized plots from all models showing consensus programs.

Shown are efficiency frontiers for all 5 models, with the 120 consensus programs marked. All vertical axes are normalized to within-model predictions, as in Figures 1 and 2.