Evaluation of the lung cancer risks at which to screen ever- and never-smokers: screening rules applied to the PLCO and NLST cohorts.

BACKGROUND: Lung cancer risks at which individuals should be screened with computed tomography (CT) for lung cancer are undecided. This study's objectives are to identify a risk threshold for selecting individuals for screening, to compare its efficiency with the U.S. Preventive Services Task Force (USPSTF) criteria for identifying screenees, and to determine whether never-smokers should be screened. Lung cancer risks are compared between smokers aged 55-64 and ≥ 65-80 y. METHODS AND FINDINGS: Applying the PLCO(m2012) model, a model based on 6-y lung cancer incidence, we identified the risk threshold above which National Lung Screening Trial (NLST, n = 53,452) CT arm lung cancer mortality rates were consistently lower than rates in the chest X-ray (CXR) arm. We evaluated the USPSTF and PLCO(m2012) risk criteria in intervention arm (CXR) smokers (n = 37,327) of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). The numbers of smokers selected for screening, and the sensitivities, specificities, and positive predictive values (PPVs) for identifying lung cancers were assessed. A modified model (PLCOall2014) evaluated risks in never-smokers. At PLCO(m2012) risk ≥ 0.0151, the 65th percentile of risk, the NLST CT arm mortality rates are consistently below the CXR arm's rates. The number needed to screen to prevent one lung cancer death in the 65th to 100th percentile risk group is 255 (95% CI 143 to 1,184), and in the 30th to <65th percentile risk group is 963 (95% CI 291 to -754); the number needed to screen could not be estimated in the <30th percentile risk group because of absence of lung cancer deaths. When applied to PLCO intervention arm smokers, compared to the USPSTF criteria, the PLCO(m2012) risk ≥ 0.0151 threshold selected 8.8% fewer individuals for screening (p<0.001) but identified 12.4% more lung cancers (sensitivity 80.1% [95% CI 76.8%-83.0%] versus 71.2% [95% CI 67.6%-74.6%], p<0.001), had fewer false-positives (specificity 66.2% [95% CI 65.7%-66.7%] versus 62.7% [95% CI 62.2%-63.1%], p<0.001), and had higher PPV (4.2% [95% CI 3.9%-4.6%] versus 3.4% [95% CI 3.1%-3.7%], p<0.001). In total, 26% of individuals selected for screening based on USPSTF criteria had risks below the threshold PLCO(m2012) risk ≥ 0.0151. Of PLCO former smokers with quit time >15 y, 8.5% had PLCO(m2012) risk ≥ 0.0151. None of 65,711 PLCO never-smokers had PLCO(m2012) risk ≥ 0.0151. Risks and lung cancers were significantly greater in PLCO smokers aged ≥ 65-80 y than in those aged 55-64 y. This study omitted cost-effectiveness analysis. CONCLUSIONS: The USPSTF criteria for CT screening include some low-risk individuals and exclude some high-risk individuals. Use of the PLCO(m2012) risk ≥ 0.0151 criterion can improve screening efficiency. Currently, never-smokers should not be screened. Smokers aged ≥ 65-80 y are a high-risk group who may benefit from screening. Please see later in the article for the Editors' Summary.

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

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.

The prostate, lung, colorectal, and ovarian cancer screening trial and its associated research resource.

The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial is a large-scale research effort conducted by the National Cancer Institute. PLCO offers an example of coordinated research by both the extramural and intramural communities of the National Institutes of Health. The purpose of this article is to describe the PLCO research resource and how it is managed and to assess the productivity and the costs associated with this resource. Such an in-depth analysis of a single large-scale project can shed light on questions such as how large-scale projects should be managed, what metrics should be used to assess productivity, and how costs can be compared with productivity metrics. A comprehensive publication analysis identified 335 primary research publications resulting from research using PLCO data and biospecimens from 2000 to 2012. By the end of 2012, a total of 9679 citations (excluding self-citations) have resulted from this body of research publications, with an average of 29.7 citations per article, and an h index of 45, which is comparable with other large-scale studies, such as the Nurses' Health Study. In terms of impact on public health, PLCO trial results have been used by the US Preventive Services Task Force in making recommendations concerning prostate and ovarian cancer screening. The overall cost of PLCO was $454 million over 20 years, adjusted to 2011 dollars, with approximately $37 million for the collection, processing, and storage of biospecimens, including blood samples, buccal cells, and pathology tissues.

Radiation-related cancer risks from CT colonography screening: a risk-benefit analysis.

OBJECTIVE: The purpose of this study was to estimate the ratio of cancers prevented to induced (benefit-risk ratio) for CT colonography (CTC) screening every 5 years from the age of 50 to 80 years. MATERIALS AND METHODS: Radiation-related cancer risk was estimated using risk projection models based on the National Research Council's Biological Effects of Ionizing Radiation (BEIR) VII Committee's report and screening protocols from the American College of Radiology Imaging Network's National CT Colonography Trial. Uncertainty intervals were estimated using Monte Carlo simulation methods. Comparative modeling with three colorectal cancer microsimulation models was used to estimate the potential reduction in colorectal cancer cases and deaths. RESULTS: The estimated mean effective dose per CTC screening study was 8 mSv for women and 7 mSv for men. The estimated number of radiation-related cancers resulting from CTC screening every 5 years from the age of 50 to 80 years was 150 cases/100,000 individuals screened (95% uncertainty interval, 80-280) for men and women. The estimated number of colorectal cancers prevented by CTC every 5 years from age 50 to 80 ranged across the three microsimulation models from 3580 to 5190 cases/100,000 individuals screened, yielding a benefit-risk ratio that varied from 24:1 (95% uncertainty interval, 13:1-45:1) to 35:1 (19:1-65:1). The benefit-risk ratio for cancer deaths was even higher than the ratio for cancer cases. Inclusion of radiation-related cancer risks from CT examinations performed to follow up extracolonic findings did not materially alter the results. CONCLUSION: Concerns have been raised about recommending CTC as a routine screening tool because of potential harms including the radiation risks. Based on these models, the benefits from CTC screening every 5 years from the age of 50 to 80 years clearly outweigh the radiation risks.