A Comparative Modeling Analysis of Risk-Based Lung Cancer Screening Strategies

Background: Risk-prediction models have been proposed to select individuals for lung cancer screening. However, their longterm effects are uncertain. This study evaluates long-term benefits and harms of risk-based screening compared with current United States Preventive Services Task Force (USPSTF) recommendations. Methods: Four independent natural history models were used to perform a comparative modeling study evaluating longterm benefits and harms of selecting individuals for lung cancer screening through risk-prediction models. In total, 363 riskbased screening strategies varying by screening starting and stopping age, risk-prediction model used for eligibility (Bach, PLCOm2012, or Lung Cancer Death Risk Assessment Tool [LCDRAT]), and risk threshold were evaluated for a 1950 US birth cohort. Among the evaluated outcomes were percentage of individuals ever screened, screens required, lung cancer deaths averted, life-years gained, and overdiagnosis. Results: Risk-based screening strategies requiring similar screens among individuals ages 55–80 years as the USPSTF criteria (corresponding risk thresholds: Bach ¼ 2.8%; PLCOm2012 ¼ 1.7%; LCDRAT ¼ 1.7%) averted considerably more lung cancer deaths (Bach ¼ 693; PLCOm2012 ¼ 698; LCDRAT ¼ 696; USPSTF ¼ 613). However, life-years gained were only modestly higher (Bach ¼ 8660; PLCOm2012 ¼ 8862; LCDRAT ¼ 8631; USPSTF ¼ 8590), and risk-based strategies had more overdiagnosed cases (Bach ¼ 149; PLCOm2012 ¼ 147; LCDRAT ¼ 150; USPSTF ¼ 115). Sensitivity analyses suggest excluding individuals with limited life expectancies (<5 years) from screening retains the life-years gained by risk-based screening, while reducing overdiagnosis by more than 65.3%. Conclusions: Risk-based lung cancer screening strategies prevent considerably more lung cancer deaths than current recommendations do. However, they yield modest additional life-years and increased overdiagnosis because of predominantly selecting older individuals. Efficient implementation of risk-based lung cancer screening requires careful consideration of life expectancy for determining optimal individual stopping ages.

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