IMPORTANCE The US Preventive Services Task Force (USPSTF) is updating its 2013 lung cancer screening guidelines, which recommend annual screening for adults aged 55 through 80 years who have a smoking history of at least 30 pack-years and currently smoke or have quit within the past 15 years. OBJECTIVE To inform the USPSTF guidelines by estimating the benefits and harms associated with various low-dose computed tomography (LDCT) screening strategies. DESIGN, SETTING, AND PARTICIPANTS Comparative simulation modeling with 4 lung cancer natural history models for individuals from the 1950 and 1960 US birth cohorts who were followed up from aged 45 through 90 years. EXPOSURES Screening with varying starting ages, stopping ages, and screening frequency. Eligibility criteria based on age, cumulative pack-years, and years since quitting smoking (risk factor-based) or on age and individual lung cancer risk estimation using risk prediction models with varying eligibility thresholds (risk model-based). A total of 1092 LDCT screening strategies were modeled. Full uptake and adherence were assumed for all scenarios. MAIN OUTCOMES AND MEASURES Estimated lung cancer deaths averted and life-years gained (benefits) compared with no screening. Estimated lifetime number of LDCT screenings, false-positive results, biopsies, overdiagnosed cases, and radiation-related lung cancer deaths (harms). RESULTS Efficient screening programs estimated to yield the most benefits for a given number of screenings were identified. Most of the efficient risk factor-based strategies started screening at aged 50 or 55 years and stopped at aged 80 years. The 2013 USPSTF-recommended criteria were not among the efficient strategies for the 1960 US birth cohort. Annual strategies with a minimum criterion of 20 pack-years of smoking were efficient and, compared with the 2013 USPSTF-recommended criteria, were estimated to increase screening eligibility (20.6%-23.6% vs 14.1% of the population ever eligible), lung cancer deaths averted (469-558 per 100 000 vs 381 per 100 000), and life-years gained (6018-7596 per 100 000 vs 4882 per 100 000). However, these strategies were estimated to result in more false-positive test results (1.9-2.5 per person screened vs 1.9 per person screened with the USPSTF strategy), overdiagnosed lung cancer cases (83-94 per 100 000 vs 69 per 100 000), and radiation-related lung cancer deaths (29.0-42.5 per 100 000 vs 20.6 per 100 000). Risk model-based vs risk factor-based strategies were estimated to be associated with more benefits and fewer radiation-related deaths but more overdiagnosed cases. CONCLUSIONS AND RELEVANCE Microsimulation modeling studies suggested that LDCT screening for lung cancer compared with no screening may increase lung cancer deaths averted and life-years gained when optimally targeted and implemented. Screening individuals at aged 50 or 55 years through aged 80 years with 20 pack-years or more of smoking exposure was estimated to result in more benefits than the 2013 USPSTF-recommended criteria and less ...

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Background Risk-prediction models have been proposed to select individuals for lung cancer screening. However, their long-term 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 long-term benefits and harms of selecting individuals for lung cancer screening through risk-prediction models. In total, 363 risk-based 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 = 2.8%; PLCOm2012 = 1.7%; LCDRAT = 1.7%) averted considerably more lung cancer deaths (Bach = 693; PLCOm2012 = 698; LCDRAT = 696; USPSTF = 613). However, life-years gained were only modestly higher (Bach = 8660; PLCOm2012 = 8862; LCDRAT = 8631; USPSTF = 8590), and risk-based strategies had more overdiagnosed cases (Bach = 149; PLCOm2012 = 147; LCDRAT = 150; USPSTF = 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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