Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Ten Haaf K

PROVIDER: S-EPMC7225672 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Publications

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

Ten Haaf Kevin K Bastani Mehrad M Cao Pianpian P Jeon Jihyoun J Toumazis Iakovos I Han Summer S SS Plevritis Sylvia K SK Blom Erik F EF Kong Chung Yin CY Tammemägi Martin C MC Feuer Eric J EJ Meza Rafael R de Koning Harry J HJ

Journal of the National Cancer Institute 20200501 5

<h4>Background</h4>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.<h4>Methods</h4>Four independent natural history models were used to perform a comparative modeling study evaluating long-term benefits and harms of selecting individuals for l ...[more]

PMID: 31566216

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Project description:Background Country-specific evidence is needed to guide decisions regarding whether and how to implement lung cancer screening in different settings. For this study, we estimated the potential numbers of individuals screened and lung cancer deaths prevented in Brazil after applying different strategies to define screening eligibility. Methods We applied the Lung Cancer Death Risk Assessment Tool (LCDRAT) to survey data on current and former smokers (ever-smokers) in 15 Brazilian state capital cities that comprise 18% of the Brazilian population. We evaluated three strategies to define eligibility for screening: (1) pack-years and cessation time (≥30 pack-years and <15 years since cessation); (2) the LCDRAT risk model with a fixed risk threshold; and (3) LCDRAT with age-specific risk thresholds. Findings Among 2.3 million Brazilian ever-smokers aged 55–79 years, 21,459 (95%CI 20,532–22,387) lung cancer deaths were predicted over 5 years without screening. Applying the fixed risk-based eligibility definition would prevent more lung cancer deaths than the pack-years definition [2,939 (95%CI 2751–3127) vs. 2,500 (95%CI 2318–2681) lung cancer deaths], and with higher screening efficiency [NNS=177 (95%CI 170–183) vs. 205 (95%CI 194–216)], but would tend to screen older individuals [mean age 67.8 (95%CI 67.5–68.2) vs. 63.4 (95%CI 63.0–63.9) years]. Applying age-specific risk thresholds would allow younger ever-smokers to be screened, although these individuals would be at lower risk. The age-specific thresholds strategy would avert three-fifths (60.1%) of preventable lung cancer deaths [N = 2629 (95%CI 2448–2810)] by screening 21.9% of ever-smokers. Interpretation The definition of eligibility impacts the efficiency of lung cancer screening and the mean age of the eligible population. As implementation of lung screening proceeds in different countries, our analytical framework can be used to guide similar analyses in other contexts. Due to limitations of our models, more research would be needed.

Project description:ImportanceScreening mammography and magnetic resonance imaging (MRI) are recommended for women with ATM, CHEK2, and PALB2 pathogenic variants. However, there are few data to guide screening regimens for these women.ObjectiveTo estimate the benefits and harms of breast cancer screening strategies using mammography and MRI at various start ages for women with ATM, CHEK2, and PALB2 pathogenic variants.Design, setting, and participantsThis comparative modeling analysis used 2 established breast cancer microsimulation models from the Cancer Intervention and Surveillance Modeling Network (CISNET) to evaluate different screening strategies. Age-specific breast cancer risks were estimated using aggregated data from the Cancer Risk Estimates Related to Susceptibility (CARRIERS) Consortium for 32 247 cases and 32 544 controls in 12 population-based studies. Data on screening performance for mammography and MRI were estimated from published literature. The models simulated US women with ATM, CHEK2, or PALB2 pathogenic variants born in 1985.InterventionsScreening strategies with combinations of annual mammography alone and with MRI starting at age 25, 30, 35, or 40 years until age 74 years.Main outcomes and measuresEstimated lifetime breast cancer mortality reduction, life-years gained, breast cancer deaths averted, total screening examinations, false-positive screenings, and benign biopsies per 1000 women screened. Results are reported as model mean values and ranges.ResultsThe mean model-estimated lifetime breast cancer risk was 20.9% (18.1%-23.7%) for women with ATM pathogenic variants, 27.6% (23.4%-31.7%) for women with CHEK2 pathogenic variants, and 39.5% (35.6%-43.3%) for women with PALB2 pathogenic variants. Across pathogenic variants, annual mammography alone from 40 to 74 years was estimated to reduce breast cancer mortality by 36.4% (34.6%-38.2%) to 38.5% (37.8%-39.2%) compared with no screening. Screening with annual MRI starting at 35 years followed by annual mammography and MRI at 40 years was estimated to reduce breast cancer mortality by 54.4% (54.2%-54.7%) to 57.6% (57.2%-58.0%), with 4661 (4635-4688) to 5001 (4979-5023) false-positive screenings and 1280 (1272-1287) to 1368 (1362-1374) benign biopsies per 1000 women. Annual MRI starting at 30 years followed by mammography and MRI at 40 years was estimated to reduce mortality by 55.4% (55.3%-55.4%) to 59.5% (58.5%-60.4%), with 5075 (5057-5093) to 5415 (5393-5437) false-positive screenings and 1439 (1429-1449) to 1528 (1517-1538) benign biopsies per 1000 women. When starting MRI at 30 years, initiating annual mammography starting at 30 vs 40 years did not meaningfully reduce mean mortality rates (0.1% [0.1%-0.2%] to 0.3% [0.2%-0.3%]) but was estimated to add 649 (602-695) to 650 (603-696) false-positive screenings and 58 (41-76) to 59 (41-76) benign biopsies per 1000 women.Conclusions and relevanceThis analysis suggests that annual MRI screening starting at 30 to 35 years followed by annual MRI and mammography at 40 years may reduce breast cancer mortality by more than 50% for women with ATM, CHEK2, and PALB2 pathogenic variants. In the setting of MRI screening, mammography prior to 40 years may offer little additional benefit.

Project description:BackgroundThe optimum screening policy for lung cancer is unknown.ObjectiveTo identify efficient computed tomography (CT) screening scenarios in which relatively more lung cancer deaths are averted for fewer CT screening examinations.DesignComparative modeling study using 5 independent models.Data sourcesThe 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 populationU.S. cohort born in 1950.Time horizonCohort followed from ages 45 to 90 years.PerspectiveSocietal.Intervention576 scenarios with varying eligibility criteria (age, pack-years of smoking, years since quitting) and screening intervals.Outcome measuresBenefits 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 scenarioThe 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 analysisThe 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.LimitationsScenarios assumed 100% screening adherence. Data derived from trials with short duration were extrapolated to lifetime follow-up.ConclusionAnnual 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 sourceNational Cancer Institute.

Project description:BackgroundTargeting low-dose computed tomography (LDCT) for lung cancer screening to persons at highest risk for lung cancer mortality has been suggested to improve screening efficiency.ObjectiveTo quantify the value of risk-targeted selection for lung cancer screening compared with National Lung Screening Trial (NLST) eligibility criteria.DesignCost-effectiveness analysis using a multistate prediction model.Data sourcesNLST.Target populationCurrent and former smokers eligible for lung cancer screening.Time horizonLifetime.PerspectiveHealth care sector.InterventionRisk-targeted versus NLST-based screening.Outcome measuresIncremental 7-year mortality, life expectancy, quality-adjusted life-years (QALYs), costs, and cost-effectiveness of screening with LDCT versus chest radiography at each decile of lung cancer mortality risk.Results of base-case analysisParticipants at greater risk for lung cancer mortality were older and had more comorbid conditions and higher screening-related costs. The incremental lung cancer mortality benefits during the first 7 years ranged from 1.2 to 9.5 lung cancer deaths prevented per 10 000 person-years for the lowest to highest risk deciles, respectively (extreme decile ratio, 7.9). The gradient of benefits across risk groups, however, was attenuated in terms of life-years (extreme decile ratio, 3.6) and QALYs (extreme decile ratio, 2.4). The incremental cost-effectiveness ratios (ICERs) were similar across risk deciles ($75 000 per QALY in the lowest risk decile to $53 000 per QALY in the highest risk decile). Payers willing to pay $100 000 per QALY would pay for LDCT screening for all decile groups.Results of sensitivity analysisAlternative assumptions did not substantially alter our findings.LimitationOur model did not account for all correlated differences between lung cancer mortality risk and quality of life.ConclusionsAlthough risk targeting may improve screening efficiency in terms of early lung cancer mortality per person screened, the gains in efficiency are attenuated and modest in terms of life-years, QALYs, and cost-effectiveness.Primary funding sourceNational Institutes of Health (U01NS086294).

Project description:Background:Although risk-based selection of ever-smokers for screening could prevent more lung cancer deaths than screening according to the U.S. Preventive Services Task Force (USPSTF) guidelines, it preferentially selects older ever-smokers with shorter life expectancies due to comorbidities. Objective:To compare selection of ever-smokers for screening based on gains in life expectancy versus lung cancer risk. Design:Cohort analyses and model-based projections. Setting:U.S. population of ever-smokers aged 40 to 84 years. Participants:130 964 National Health Interview Survey participants, representing about 60 million U.S. ever-smokers during 1997 to 2015. Intervention:Annual computed tomography (CT) screening for 3 years versus no screening. Measurements:Estimated number of lung cancer deaths averted and life-years gained after development of a mortality model. Results:Using the calibrated and validated mortality model in U.S. ever-smokers aged 40 to 84 years and selecting 8.3 million ever-smokers to match the number selected by the USPSTF criteria in 2013 to 2015, the analysis estimated that life-gained-based selection would increase the total life expectancy from CT screening (633 400 vs. 607 800 years) but prevent fewer lung cancer deaths (52 600 vs. 55 000) compared with risk-based selection. The 1.56 million persons selected by the life-gained-based strategy but not the risk-based strategy were younger (mean age, 59 vs. 75 years) and had fewer comorbidities (mean, 0.75 vs. 3.7). Limitation:Estimates are model-based and assume implementation of lung cancer screening with short-term effectiveness similar to that from trials. Conclusion:Life-gained-based selection could maximize the benefits of lung cancer screening in the U.S. population by including ever-smokers who have both high lung cancer risk and long life expectancy. Primary Funding Source:Intramural Research Program of the National Cancer Institute, National Institutes of Health.

Project description:ImportanceIn 2018, only half of US women obtained all evidence-based cancer screenings. This proportion may have declined during the COVID-19 pandemic because of social distancing, high-risk factors, and fear.ObjectiveTo evaluate optimal screening strategies in women who obtain some, but not all, US Preventive Services Task Force (USPSTF)-recommended cancer screenings.Design, setting, and participantsThis modeling study was conducted from January 31, 2017, to July 20, 2020, and used 4 validated mathematical models from the National Cancer Institute's Cancer Intervention and Surveillance Modeling Network using data from 20 million simulated women born in 1965 in the US.InterventionsForty-five screening strategies were modeled that combined breast, cervical, colorectal, and/or lung cancer (LC) screenings; restricted to 1, 2, 3 or 4 screenings per year; or all eligible screenings once every 5 years.Main outcomes and measuresModeled life-years gained from restricted cancer screenings as a fraction of those attainable from full compliance with USPSTF recommendations (maximum benefits). Results were stratified by LC screening eligibility (LC-eligible/ineligible). We repeated the analysis with 2018 adherence rates, evaluating the increase in adherence required for restricted screenings to have the same population benefit as USPSTF recommendations.ResultsThis modeling study of 20 million simulated US women found that it was possible to reduce screening intensity to 1 carefully chosen test per year in women who were ineligible for LC screening and 2 tests per year in eligible women while maintaining 94% or more of the maximum benefits. Highly ranked strategies screened for various cancers, but less often than recommended by the USPSTF. For example, among LC-ineligible women who obtained just 1 screening per year, the optimal strategy frequently delayed breast and cervical cancer screenings by 1 year and skipped 3 mammograms entirely. Among LC-eligible women, LC screening was essential; strategies omitting it provided 25% or less of the maximum benefits. The top-ranked strategy restricted to 2 screenings per year was annual LC screening and alternating fecal immunochemical test with mammography (skipping mammograms when due for cervical cancer screening, 97% of maximum benefits). If adherence in a population of LC-eligible women obtaining 2 screenings per year were to increase by 1% to 2% (depending on the screening test), this model suggests that it would achieve the same benefit as USPSTF recommendations at 2018 adherence rates.Conclusions and relevanceThis modeling study of 45 cancer screening strategies suggests that women who are noncompliant with cancer screening guidelines may be able to reduce USPSTF-recommended screening intensity with minimal reduction in overall benefits.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

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