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JAMA. Author manuscript; available in PMC 2016 June 09.
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Published in final edited form as:

JAMA. 2016 June 7; 315(21): 2300–2311. doi:10.1001/jama.2016.6255.

Development and validation of risk models to select ever-

smokers for CT lung-cancer screening
Hormuzd A. Katki, Ph.D.1,*, Stephanie A. Kovalchik, Ph.D.2, Christine D. Berg, M.D.1,3, Li C.
Cheung, M.S.4, and Anil K. Chaturvedi, Ph.D.1,*
1Divisionof Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of
Health, DHHS, Bethesda, MD, USA
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2Institute of Sport, Exercise and Active Living, Victoria University, Melbourne, Australia
3Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medicine,
Baltimore, MD, USA
4Information Management Services Inc., Calverton, MD, USA

Abstract
Importance—The US Preventive Services Task Force (USPSTF) recommends computed-
tomography (CT) lung-cancer screening for ever-smokers ages 55-80 years who smoked at least
30 pack-years with no more than 15 years since quitting. However, selecting ever-smokers for
screening using individualized lung-cancer risk calculations may be more effective and efficient
than current USPSTF recommendations.
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Objective—Comparison of modeled outcomes from risk-based CT lung-screening strategies

versus USPSTF recommendations.

Design/Setting/Participants—Empirical risk models for lung-cancer incidence and death in

the absence of CT screening using data on ever-smokers from the Prostate, Lung, Colorectal and
Ovarian Cancer Screening Trial (PLCO; 1993-2009) control group. Covariates included age,
education, sex, race, smoking intensity/duration/quit-years, Body Mass Index, family history of
lung-cancer, and self-reported emphysema. Model validation in the chest radiography groups of
the PLCO and the National Lung Screening Trial (NLST; 2002-2009), with additional validation
of the death model in the National Health Interview Survey (NHIS; 1997-2001), a representative
sample of the US. Models applied to US ever-smokers ages 50-80 (NHIS 2010-2012) to estimate
outcomes of risk-based selection for CT lung-screening, assuming screening for all ever-smokers
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yields the percent changes in lung-cancer detection and death observed in the NLST.

Exposure—Annual CT lung-screening for 3 years.

*
Corresponding authors:HAK: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Dr.,
Room 7E606, Bethesda, MD 20892, Phone: 240-276-7423, Fax: 240-276-7838, katkih@[Link]; AKC: Division of Cancer
Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Dr., Room 6E238, Bethesda, MD 20892, Phone:
240-276-7193, chaturva@[Link].
Conflicts of Interest: Dr. Christine Berg receives consulting fees from Medial ES, LLC, a company that is developing algorithms
from routine blood tests that may indicate an increased risk of malignancy.
Access to Data: Hormuzd A. Katki had full access to all the data in the study and takes responsibility for the integrity of the data and
the accuracy of the data analysis.
 Katki et al. Page 2

Main Outcomes and Measures—Model validity: calibration (number of model-predicted

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cases divided by number of observed cases (Estimated/Observed)) and discrimination (Area-

Under-Curve (AUC)). Modeled screening outcomes: estimated number of screen-avertable lung-
cancer deaths, estimated screening effectiveness (number needed to screen (NNS) to prevent 1
lung-cancer death).

Results—Lung-cancer incidence and death risk models were well-calibrated in PLCO and
NLST. The lung-cancer death model calibrated and discriminated well for US ever-smokers ages
50-80 (NHIS 1997-2001: Estimated/Observed=0.94, 95%CI=0.84-1.05; AUC=0.78,
95%CI=0.76-0.80). Under USPSTF recommendations, the models estimated 9.0 million US ever-
smokers would qualify for lung-cancer screening and 46,488 (95%CI=43,924-49,053) lung-cancer
deaths were estimated as screen-avertable over 5 years (estimated NNS=194, 95%CI=187-201). In
contrast, risk-based selection screening the same number of ever-smokers (9.0 million) at highest
5-year lung-cancer risk (≥1.9%), was estimated to avert 20% more deaths (55,717;
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95%CI=53,033-58,400) and was estimated to reduce the estimated NNS by 17% (NNS=162,
95%CI=157-166).

Conclusions and Relevance—Among a cohort of US ever-smokers age 50-80 years,

application of a risk-based model for CT screening for lung cancer compared with a model based
on USPSTF recommendations was estimated to be associated with a greater number of lung-
cancer deaths prevented over 5 years along with a lower NNS to prevent 1 lung-cancer death.

Keywords
precision medicine; risk-based medicine; heterogeneity of treatment effect; risk modeling;
precision prevention; smoking; USPSTF
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INTRODUCTION
1
Lung-cancer is the most common cause of cancer death in the United States. The National
Lung Screening Trial (NLST) demonstrated a 20% reduction in lung-cancer mortality with 3
rounds of low-dose computed tomography (CT) screening as compared with chest
2
radiography, over a mean follow-up of 6.4 years. Consequently, the US Preventive Services
Task Force (USPSTF) and the US Centers for Medicare and Medicaid Services (CMS) now
recommend annual CT screening for a risk-factor-based subgroup of smokers—current and
former smokers ages 55-80 years and 55-77 years, respectively, with at least 30 pack-years
3
of smoking and, for former smokers, no more than 15 years since quitting. ,4 These were
largely based on the entry criteria for the NLST as well as microsimulation models that
5
considered subgroups defined by age/pack-year/quit-year criteria. ,6
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Selecting individuals at highest lung-cancer risk, as determined by individual risk

calculations (i.e. risk-based selection) rather than by risk-factor-based subgroups, might lead
3 10
to more efficient screening. ,7- In the NLST, 88% of CT-prevented lung-cancer deaths
occurred in the 60% of participants at highest risk, while the 20% of participants at lowest
11
risk accounted for only 1% of CT-prevented lung-cancer deaths. The cost-effectiveness of
12
CT screening also increased with lung-cancer risk in the NLST. Risk-based selection more
precisely delineates the benefits and harms of screening by accommodating detailed

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3
information on all lung-cancer risk factors. Risk-based selection also enforces consistency
of screening recommendations by accommodating “equal management of people at equal
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13
risk”. However, to our knowledge, there are currently no risk tools for lung-cancer that
have been validated in representative samples of the US population. Likewise, empirical
evidence is lacking for the superiority of risk-based lung-cancer screening in the US.

In this study, we sought to develop and validate empirical lung-cancer incidence and death
risk models generalizable to US smokers, as well as an empirical model for risk of false-
positive CT screen. Models were applied to a contemporary cohort of US ever-smokers to
investigate estimated outcomes from various risk-based selection strategies versus current
USPSTF recommendations, for “NLST-like” screening (3 yearly CT screens) with 5-years
follow-up.

METHODS
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Data sources
Data was used from two lung-cancer screening trials in the US—The Prostate, Lung,
Colorectal, and Ovarian (PLCO) Cancer Screening Trial and the NLST— as well as data
from the NHIS, a representative sample of the US population. From 1993-2001, the PLCO
trial randomized 154,901 US men and women ages 55-74 years to receive four annual
posterior-anterior chest radiographs (three in never-smokers) or the standard of care, and
14
concluded that chest radiography screening did not reduce lung-cancer mortality. The most
recent follow-up data for PLCO was available through December 2009. From 2002-2004,
the NLST randomized 53,454 US smokers ages 55-74, with at least 30 pack-years of
smoking and no more than 15 years since smoking cessation to receive three annual rounds
2
of low-dose CT or posterior-anterior chest radiography. The NLST dataset included
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outcomes accrued through January 15, 2009, the latest date for censoring lung-cancer death
for the primary analysis. The NHIS is an annual cross-sectional, multi-stage probability
sample of approximately 87,500 individuals representing the non-institutionalized civilian
15
US population. NHIS data collected through 2004 have been linked with the National
16
Death Index (NDI), with follow-up through December 31, 2006. The National Institutes of
Health Office of Human Subjects Research deemed this study exempt from IRB review.

Statistical Analyses
Development and validation of risk models—Absolute risk models were developed
to predict five-year cumulative risk of lung-cancer incidence and lung-cancer death using
data on ever-smokers within the control group of the PLCO trial. PLCO data allowed us to
develop valid models for both USPSTF-eligible and –ineligible smokers. Cox hazard-ratio
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models on time since interview were used, and accounted for life expectancy by fitting a
17 11
hazard-ratio model for competing causes of death. Compared to previous work , each
submodel (lung-cancer incidence, lung-cancer death, and death by other causes) now
includes more self-reported demographic (age, gender, race, education, body-mass
index(BMI)), self-reported clinical (history of emphysema and lung-cancer family-history),
and self-reported smoking (cigarettes per day, smoking duration, and smoking pack-years

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and quit-years) variables. Variables and parameterization for continuous variables were
selected using the Akaike Information Criterion. See Supplemental Methods for details.
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Validation of the lung-cancer death model for US ever-smokers ages 50-80 years used NHIS
surveys 1997-2001 because age at smoking initiation was not systematically collected before
1997. Via NDI linkage through 2006, each NHIS participant had at least five years of
follow-up for lung-cancer death. Multiple-imputation was used to account for the <2.5%
missing information on BMI, race, education, or quit-years (Table S6). Because only 5.5%
of participants reported family history of lung cancer, it can be conservatively assumed that
those with missing family history information had no family history. For former smokers,
the number of cigarettes smoked per day was systematically missing, for which a special
imputation model was developed (Supplemental Methods).

Because there is no US-representative data including both lung-cancer incidence and risk
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factors, validation of the lung-cancer incidence model used data on ever-smokers in the chest
radiography groups of the PLCO and the NLST. The PLCO chest radiography group
14
experienced only slightly increased lung-cancer detection.

Model validity was assessed by calibration (the ratio of number of model-predicted cases to
the number of observed cases (Estimated/Observed)) and discrimination (the Area-Under-
Curve (AUC) statistic) (Supplemental Methods).

A quadrinomial logistic regression model was developed to estimate an individual’s

probability of 0, 1, 2, or 3 false-positive screens over 3 rounds of CT screening as a function
of their modeled lung-cancer risk. The false-positive probability is the joint probability of
having a positive CT screen and not being diagnosed with lung cancer within 1 year after
diagnostic follow-up initiated within 1 year after the positive screen (see Supplemental
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Methods). This model for false-positive risk, based on the NLST data, was assumed to hold
for lung-screening programs in the US.

All p-values are 2-sided and p<0.05 was declared significant.

US-representative estimates of CT lung-screening outcomes—The empirical

models were applied to a contemporary US population of ever-smokers ages 50-80 years
(NHIS 2010-2012), to estimate potential modeled outcomes associated with different
strategies for selecting ever-smokers for NLST-like CT screening. 5-year risks of lung-
cancer and lung-cancer death (in the absence and presence of NLST-like CT screening) and
risk of false-positive CT were estimated for each NHIS participant. These estimates used a
key assumption that NLST observations (i.e. 3 yearly CT screens would reduce lung-cancer
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mortality by 20.4% and increase lung-cancer detection by 12.4% over 5 years) are
applicable to all US ever-smokers, regardless of their smoking history (Supplemental
Methods).

For each selection strategy, the models were used to estimate numbers of smokers screened,
lung-cancer deaths averted, lung-cancers detected, and false-positive CTs. Screening
program metrics were estimated: “screening effectiveness” (defined as the number needed to
screen (NNS) to prevent one lung-cancer death), “screening efficiency” (defined as the

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number of false-positive CTs per prevented lung-cancer death), and the number of extra
lung-cancers diagnosed per prevented lung-cancer death.
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Outcomes were compared based on USPSTF-eligibility versus different strategies for

selecting individuals for CT screening based on lung-cancer risk thresholds. For illustrative
purposes, two risk-based strategies were considered at length: (1) “fixed population-size”—
choosing the lung-cancer risk threshold such that the number screened matches the number
of USPSTF-eligible smokers in the US, and (2) “modeled fixed effectiveness”— choosing
the lung-cancer risk threshold such that the NNS matches the NNS based on screening all
18
USPSTF-eligible smokers in the US. All analyses were conducted in R , and used the
19
survey package to account for survey weights (see Supplemental Methods).

RESULTS
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Risk models
Table 1 summarizes the data sources used to fit, validate, and apply each risk model. Tables
2 shows characteristics of all cohorts. Table 3 shows risk factors in the hazard-ratio
submodels for lung-cancer incidence, lung-cancer death, and competing mortality.
Predictors included age, race, gender, education, BMI, family history of lung cancer, self-
reported emphysema, pack-years of smoking, duration of smoking, years since smoking
cessation, and packs smoked per day (Table 3). Risk of false-positive CT screens increased
with lung-cancer risk (Table S1).

The lung-cancer incidence model was validated in the chest radiography group of the NLST
(Estimated/Observed=1.06, 95%CI=0.98-1.13; AUC=0.70, 95%CI=0.69-0.72), in the PLCO
radiography group ever-smokers (Estimated/Observed=0.94, 95%CI=0.87-1.02; AUC=0.80,
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95%CI=0.78-0.81), and within subgroups (Table S2).

The lung-cancer death model was validated for US ever-smokers ages 50-80 in the
1997-2001 NHIS, both overall (Estimated/Observed=0.94, 95%CI=0.84-1.05; AUC=0.78,
95%CI=0.76-0.80) and within subgroups (Table S3). The model was also validated in PLCO
radiography group ever-smokers, both overall (Estimated/Observed=1.08,
95%CI=0.97-1.20; AUC=0.81, 95%CI=0.79-0.83) and within subgroups (Table S4).

Lung-cancer mortality in the NLST radiography group appears to be 24% lower than that
expected from the lung-cancer death model that calibrated well to PLCO and to nationally-
representative NHIS data. Although this does not affect internal validity of the NLST,
modeling lung-cancer screening outcomes for the US was affected (See Supplemental
Results, Table S4, and Discussion).
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Modeled outcomes associated with 5-year effect of risk-based NLST-like CT screening in

the US
Based on NHIS 2010-2012, there were an estimated 43.4 million ever-smokers ages 50-80
years in the US. Assuming that the NLST mortality reduction of 20.4% applies also to all
ever-smokers independently of exposure level, an NLST-like CT screening program was
modeled to prevent an estimated 82,245 lung-cancer deaths (95%CI=79,255-85,235) over 5

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years (Table 4). Screening only the 9.0 million individuals (21%) eligible by USPSTF
recommendations was modeled to prevent an estimated 46,488 (95%CI=43,924-49,053)
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lung-cancer deaths over 5 years (57% of estimated CT-preventable deaths). Instead, the risk-
based fixed population-size strategy of screening the 9.0 million smokers ages 50-80 at
highest 5-year risk of lung-cancer (≥1.9%) was modeled to prevent an estimated 55,717
(95%CI=53,033-58,400) lung-cancer deaths (68% of estimated CT-preventable deaths). This
was a 20% relative increase in estimated CT-preventable deaths versus USPSTF
recommendations (11% absolute increase; p<0.0001), yet screening the same number of
smokers. Furthermore, compared to USPSTF recommendations, the risk-based fixed
USPSTF sample-size strategy was modeled to have greater estimated screening effectiveness
(NNS=194 (95%CI=187-201) vs. 162 (95%CI=157-166), p<0.0001) and estimated
screening efficiency (fewer false-positive screens per prevented death: 133
(95%CI=128-137) vs. 116 (95%CI=113-119), p<0.0001), while maintaining the estimated
ratio of extra lung-cancers diagnosed per prevented death (0.93 (95%CI=0.93-0.94) vs. 0.91
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(95%CI=0.91-0.92), p<0.0001) (Table 4).

The risk-based modeled fixed effectiveness strategy maintains the same estimated NNS=194
as modeled for the USPSTF recommendations. This strategy would select for CT screening
an extra 3.1 million individuals (12.1 million total; 28% of ever-smokers ages 50-80) at
highest 5-year lung-cancer risk (≥1.7%), and was modeled to prevent an estimated 62,382
(95%CI=59,567-65,196) lung-cancer deaths (76% of CT-preventable deaths) over 5 years.
Compared to the USPSTF guidelines, this was a 34% relative increase in modeled CT-
preventable deaths (19% absolute increase; p<0.0001), while maintaining the same
estimated screening efficiency (false-positive screens per prevented death: 134
(95%CI=131-138) vs. 133 (95%CI=128-137), p=0.5) and the same estimated ratio of extra
lung-cancers diagnosed per prevented death (0.92 (95%CI=0.92-0.93) vs. 0.93
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(95%CI=0.92-0.93), p=0.006) (Table 4).

Figure 1 shows modeled 5-year outcomes for risk-based CT screening strategies over a
range of lung-cancer risk thresholds. For example, preventing 90% of CT-preventable lung-
cancer deaths was estimated to require screening the 49% of ever-smokers at highest lung-
cancer risk (≥0.7%; 21.2 million people), yielding an estimated NNS of 287
(95%CI=279-295) per prevented death and an estimated 185 (95%CI=181-190) false-
positives per prevented death. Strategies below the curve, such as USPSTF and CMS
recommendations, were estimated as having less screening effectiveness than risk-based
strategies.

Comparison of USPSTF-eligible population to risk-based populations

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Risk-based strategies retain the highest-risk USPSTF-eligible smokers but replace lower-risk
USPTF-eligible smokers with higher-risk USPSTF-ineligible smokers. Compared to
USPSTF-eligibility, risk-based screening strategies preferentially include more current
smokers overall, more low-intensity long-term current-smokers, and more high-intensity
former-smokers who have quit for more than 15 years (Table 5).

In the risk-based fixed population-size strategy, 36% of the USPSTF-eligible smokers are
replaced by an equal number of USPSTF-ineligible smokers at much higher lung-cancer risk

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(average 5-year lung-cancer risk=1.3% vs. 3.2%) and lower NNS (647 vs. 226) (Table S5a).
The replacements are preferentially current smokers, ages 65-80 years, African-Americans,
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less educated and lower BMI individuals, those with emphysema, and those with a family
history of lung-cancer (Table S5a). The subgroup of replacements who smoked less than 30
pack-years tend to be current long-term (45+ year) smokers, but 99% of whom smoke less
than 1 pack per day, and 61% of whom smoke less than half a pack per day (Table S5a). This
subgroup is also majority female and disproportionately African-American. The subgroup of
replacements who quit more than 15 years ago were high-intensity smokers, almost all of
whom smoked at least 30 pack-years, and 53% smoked at least 45 pack-years (Table S5a).

Similar conclusions hold for the risk-based modeled fixed effectiveness strategy, which
replaces 24% of the USPSTF-eligible with more USPSTF-ineligible smokers at higher lung-
cancer risk (average 5-year lung-cancer risk=1.1% vs. 2.6%) and lower NNS (813 vs. 281)
(Table S5b).
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DISCUSSION
Empirical individual risk models were developed, validated, and applied to US health survey
data to estimate the 5-year effect of NLST-like CT lung-cancer screening (3 annual screens)
in the US. The risk models validate well in US research cohorts (PLCO and NLST) as well
as in the US general population (NHIS), suggesting transportability of these models. The
key observation from the models is that compared to selecting risk-factor-based subgroups
for screening (such as current USPSTF recommendations), individual-risk-based selection of
smokers was estimated to prevent more deaths, improve screening effectiveness (defined as
the number needed to screen to prevent 1 lung-cancer death) and improve screening
efficiency (defined as the ratio of false-positive CT screens to prevented deaths).
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The superior performance of risk-based screening is highlighted by the estimate that 90% of
CT-preventable lung-cancer deaths are possibly preventable by a risk-based strategy that
screens only 49% of US ever-smokers ages 50-80. This strategy is modeled to screen 287
individuals per prevented death, which may be comparably effective as other cancer
20
screening programs.

Risk-based screening strategies appear superior to USPSTF recommendations because they

preferentially replace the 36% of the USPSTF-eligible who are low-risk, low-benefit, ever-
smokers (5-year lung-cancer risk=1.3% and NNS=647) with USPSTF-ineligible high-risk,
high-benefit, ever-smokers (5-year lung-cancer risk=3.2% and NNS=226). These USPSTF-
ineligible high-risk individuals cannot be identified by subgroups and require a risk
21
calculation to identify, such as the 22% who smoke less than 30 pack-years , the 13% who
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smoke less than a half-pack per-day, or the 14% who quit smoking more than 15 years ago.
Conversely, 36% of USPSTF-eligible individuals are actually at low risk and thus may
benefit less from screening than would be recognized without a risk calculation. Risk-based
selection would also increase the number of African-Americans and women selected for CT
lung screening. Post-hoc NLST analyses suggest possibly higher efficacy of CT lung
22
screening for women.

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Substantially higher effectiveness of an NLST-like CT-screening program among USPSTF-

2
eligible smokers in the US was estimated than that observed in the NLST (NNS=194 vs.
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320, respectively). Although including individuals ages 75-80 (per USPSTF

recommendations) increases effectiveness, the bigger contributor is the substantially lower
lung-cancer mortality in the NLST than expected based on lung-cancer mortality rates in the
PLCO and the US (NHIS). Consequently, the benefits of CT-screening in the US could be
2 23
higher than that observed in the NLST , or estimated using NLST rates , or estimated by
24
microsimulation models calibrated to the NLST . The deficit in lung-cancer mortality in the
NLST was not fully explained by study-specific differences in risk factors, lung-cancer
incidence, treatments, or histology/stage at lung-cancer diagnosis. A small mortality
reduction from chest radiography in the NLST, but not PLCO, cannot be ruled out. These
observations demonstrate the importance of validating risk models to population-
representative data, such as the NHIS, rather than to research studies, which can have
25
healthy-volunteer effects. ,26
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Our empirical methodology has limitations. The estimates are model-based rather than
directly observed outcomes. The estimates presume the implementation of screening
programs in the US with short-term performance similar to the NLST. In particular, the key
assumption was that that the 20.4% reduction in lung-cancer mortality and the 12.4%
increase in lung-cancer detection from CT screening observed in the NLST would be the
same in NLST-ineligible smokers in the US population. Notably, in the NLST, the mortality
reduction and increased lung cancer detection were unrelated to modeled lung-cancer risk,
lending support to the validity of the assumption. The NLST-based model for false-positive
CT screens was assumed to apply to lung-screening programs in the US. Screening
performance may change with innovation, for example, if CT findings are classified by
27
Lung-RADS rather than NLST protocols. Our work contrasts with microsimulation-based
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5
estimates ,6 in that, to avoid extrapolation beyond the observed NLST follow-up, only the
short-term effect of an NLST-like CT screening program in the contemporary US population
was considered. Since the NHIS does not collect cancer incidence, the lung-cancer incidence
model was validated only in research cohorts. In addition, there is no external data for
validating the model for false-positive risk.

Risk-based selection for screening is justified only if the benefits and harms of screening
primarily depend on individual cancer risk, in that, two individuals with different
combinations of risk factors but equal modeled risk would have similar outcomes. If true,
this implies the principle of “equal management of people at equal risk,” which provides a
intellectual framework for the development of simplified and consistent recommendations
13
for risk-based precision medicine. This principle was adopted as the basis of current risk-
28 30
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based cervical-cancer screening recommendations - and underlies the official risk-based

31
decision aid. For lung cancer, however, this principle may not hold for certain high-risk
subgroups that may be at increased risk of procedure-related complications, such as
individuals with chronic obstructive pulmonary disease. Indeed, NLST individuals with
multiple pulmonary comorbidities did not benefit from CT screening, despite having a high
11
modeled lung-cancer risk.

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However, implementing risk-based screening in clinical practice poses many challenges. The
models provide estimates that could be useful for justifying a cost-effective risk threshold to
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define screening eligibility. Risk thresholds could be based on either lung-cancer

32 36
incidence - or mortality, which are highly correlated. Although our incidence model and
36
the PLCOm2012 incidence model were fit to data from the PLCO, the models use different
predictors and are of different forms (our model is a Cox hazard-ratio model accounting for
competing mortality; PLCOm2012 is a logistic-regression model). In the clinic, accurate and
37 39
user-friendly risk-based decision aids - are required to lay the foundation for shared
4
decision-making. Although risk communication is challenging, it is an evolving field of
40
research. Much research remains to be done to develop and evaluate shared decision-
making processes to make precision prevention a reality.

Although CT screening can reduce lung-cancer mortality by approximately 20%, the

majority of lung-cancer deaths are not screen-preventable at this time. The best way for
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smokers to avoid lung-cancer, and all smoking-related illness, remains to quit smoking as
early as possible.

Conclusions
Among a cohort of US ever-smokers age 50-80 years, application of a risk-based model for
CT screening for lung cancer compared with a model based on USPSTF recommendations
was estimated to be associated with a greater number of lung cancer deaths prevented over 5
years along with a lower NNS to prevent 1 lung cancer death.

Supplementary Material
Refer to Web version on PubMed Central for supplementary material.
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Acknowledgments
Funding/Support: This study was supported by the Intramural Research Program of the US National Institutes of
Health/National Cancer Institute.

Role of the Sponsor: The NIH had no role in the design and conduct of the study; in the collection, analysis, and
interpretation of the data; or in the preparation, review, or approval of the manuscript.

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 Katki et al. Page 12

Key Points
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Question
What might be estimated outcomes from individual risk-based selection strategies,
compared to USPSTF recommendations, for selecting ever-smokers for CT lung-cancer
screening?

Findings
In this empirical modeling study within a cohort of US ever-smokers age 50-80 years,
application of a risk-based model for CT screening for lung cancer compared with a
model based on USPSTF recommendations was estimated to be associated with a greater
number of lung-cancer deaths prevented over 5 years along with a lower NNS to prevent
1 lung-cancer death.
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Meaning
Risk-based selection strategies for CT lung-cancer screening might improve screening
effectiveness.
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 Katki et al. Page 13
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Figure 1. 5-year modeled outcomes from different risk-based CT lung-cancer screening

strategies in US ever-smokers ages 50-80
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For example, a lung cancer risk threshold of 0.7% is estimated to screen 49% (21M) of ever-
smokers ages 50-80, prevent 90% (74,021) of preventable deaths over 5 years, screen 287
people to prevent 1 death, result in 185 false-positive CT screens per prevented death, and
diagnose 0.94 extra lung cancers per prevented death. The asterisks on the figure denote the
data markers for current USPSTF and CMS recommendations but the only axes that apply to
these two points are the estimated number and % preventable, and the estimated # and %
screened. USPSTF recommendations are estimated to screen 9.0 million (21%) of ever-
smokers age 50-80, might prevent 46,488 lung-cancer deaths over 5 years (57% of the
preventable deaths), screen 194 people to prevent one death, result in 133 false-positive CT
screens per prevented death, and diagnose 0.93 extra lung cancers per prevented death. CMS
recommendations are estimated to screen 8.7 million (20%) of ever-smokers age 50-80,
might prevent 41,559 lung-cancer deaths over 5 years (51% of the preventable deaths),
screen 208 people to prevent one death, result in 142 false-positive CT screens per prevented
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death and diagnose 0.94 extra lung cancers per prevented death. Strategies below the curve,
such as USPSTF and CMS recommendations, are estimating as having less screening
effectiveness than risk-based strategies. USPSTF recommendations are estimated as having
more screening effectiveness than CMS recommendations because CMS recommendations
exclude older smokers (ages 78-80), who can have higher risks of lung cancer.

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Table 1
Schematic of data sources used to fit, validate, and apply the lung-cancer death, lung-cancer incidence, and false-positive CT screen models

Model Data source Population

Katki et al.

Lung Cancer Incidence Model

Model development PLCO control group Ever-smokers ages 55-74

Validation #1 PLCO chest radiography Ever-smokers ages 55-74

group

Validation #2 NLST chest radiography NLST-eligible ever-smokers ages

55-74

Lung Cancer Death Model

Model development PLCO control group Ever-smokers ages 55-74

Validation #1 PLCO chest radiography Ever-smokers ages 55-74

group

Validation #2 NLST chest radiography NLST-eligible ever-smokers

group ages 55-74

Validation #3 NHIS 1997-2001 All US ever-smokers ages 50-80

False-Positive Lung Screen

Model

Model development NLST CT group NLST-eligible ever-smokers

ages 55-74

Application of all models to NHIS 2010-2012 All US ever-smokers ages 50-80

Projected outcomes from NLST-like
CT screening

Abbreviations: PLCO= Prostate, Lung, Colorectal, and Ovarian cancer screening trial; NLST=National Lung Screening Trial; NHIS= National Health Interview Survey; CT= computed tomography ; US=

JAMA. Author manuscript; available in PMC 2016 June 09.

United States
Note: The models are for lung -cancer incidence, lung-cancer death, and false-positive CT lung screen. In the presence of NLST-like CT screening, we assume that lung-cancer incidence risk is increased by
12.4%, and lung-cancer death risk is decreased by 20.4%, as observed in the NLST (see Methods and Supplemental Methods), and are applicable to all US ever-smokers, regardless of their smoking history.
All models are applied to a contemporary cohort of US ever-smokers ages 50-80 from the NHIS 2010-2012 to estimate model-based outcomes from various strategies for selecting NLST-like CT lung
screening (3 yearly CT lung screens, 5 years follow-up).
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Table 2

Characteristics for all cohorts utilized for model development, model validation, and model-based estimation of screening outcomes

PLCO control PLCO x-ray NLST x-ray NLST CT NHIS 1997-2001 NHIS 2010-2012
Katki et al.

Categories N % N % N % N % N % N %

Sample Size 39,180 100.00 39,822 100.00 26,554 100.00 26,604 100.00 29,091 100.00 18,643 100.00
Age <50 0 0.0 1 0.0 2 0.0 0 0.0 0 0.0 0 0.0

50-54 3588 9.2 3709 9.3 2685 10.1 2653 10.0 6722 23.1 3914 21.0

55-59 12635 32.2 12856 32.3 10657 40.1 10679 40.1 5604 19.3 3767 20.2

60-64 11288 28.8 11542 29 7380 27.8 7412 27.9 4734 16.3 3662 19.6

65-69 8079 20.6 8230 20.7 4136 15.6 4181 15.7 4351 15.0 3075 16.5

70-74 3588 9.2 3484 8.7 1693 6.4 1678 6.3 4150 14.3 2226 11.9

75-80 2 0 0 0.0 1 0.0 0 0.0 3530 12.1 1999 10.7

Gender Male 22694 57.9 23266 58.4 15664 59.0 15701 59.0 15375 52.9 9777 52.4

Female 16486 42.1 16556 41.6 10890 41.0 10903 41.0 13716 47.1 8866 47.6

Race White, Non-hispanic 34673 88.5 35188 88.4 23902 90.0 23920 89.9 22350 77.6 13165 71.8

Black, Non-hispanic 2180 5.6 2239 5.6 1158 4.4 1169 4.4 3439 11.9 2797 15.2

Hispanic 797 2 803 2 456 1.7 478 1.8 2540 8.8 1725 9.4

Other 1530 3.9 1569 4.0 1017 3.8 1013 3.8 464 1.6 658 3.5

Missing 19 0.0 23 0.1 21 0.1 24 0.1 298 1.0 0 0.0

Education <12 grade 3417 8.7 3462 8.7 1597 6.0 1632 6.1 7825 27.0 3423 18.4

JAMA. Author manuscript; available in PMC 2016 June 09.

HS graduate 8666 22.2 8798 22.1 6427 24.2 6258 23.5 8225 28.4 4905 26.3

Post HS, no college 5375 13.8 5337 13.4 3694 13.9 3728 14.0 2204 7.6 745 4.0

Some college 9107 23.3 9269 23.3 6075 22.9 6180 23.2 4867 16.8 3630 19.5

Bachelor’s degree 6352 16.3 6597 16.6 4432 16.7 4498 16.9 3792 13.1 4359 23.4

Postgraduate 6135 15.7 6300 15.8 3812 14.4 3776 14.2 2046 7.1 1581 8.5

Missing 128 0.3 59 0.1 517 1.9 532 2.0 132 0.5 0 0.0

BMI 18.5 or less 280 0.7 296 0.8 231 0.9 227 0.9 552 1.9 317 1.7

18.6-25 12085 31.4 12286 31.2 7303 27.6 7501 28.3 9982 35.1 5298 29.2

25.1-30 16801 43.7 16983 43.2 11470 43.4 11252 42.4 11143 39.2 6773 37.3

>30 9310 24.2 9779 24.9 7450 28.2 7535 28.4 6748 23.7 5783 31.8
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PLCO control PLCO x-ray NLST x-ray NLST CT NHIS 1997-2001 NHIS 2010-2012

Categories N % N % N % N % N % N %

Sample Size 39,180 100.00 39,822 100.00 26,554 100.00 26,604 100.00 29,091 100.00 18,643 100.00
Missing 704 1.8 478 1.2 100 0.4 89 0.3 666 2.3 472 2.5
Katki et al.

a <10 6995 18 7225 18.3 0 0.0 0 0.0 1570 15.4 2473 26.1
Pack-Years

10-19.9 7185 18.5 7623 19.3 3 0.0 1 0.0 1625 15.9 1956 20.6

20-29.9 5857 15.1 5750 14.5 679 2.6 660 2.5 1498 14.7 1404 14.8

30-39.9 4894 12.6 5005 12.7 7218 27.2 7194 27.0 1774 17.4 1344 14.2

40+ 13961 35.9 13939 35.3 18654 70.2 18749 70.5 3737 36.6 2309 24.3

Missing 288 0.7 280 0.7 0 0.0 0 0.0 18887 64.9 9157 49.1

Smoking Status Current 7925 20.2 8022 20.1 12796 48.2 12789 48.1 10475 36.0 6647 35.7

Former 31255 79.8 31800 79.9 13758 51.8 13815 51.9 18616 64.0 11996 64.3

Quit Years <5 4185 13.4 4087 12.9 5604 41.2 5697 41.7 2641 14.2 1542 12.9

5-9.9 3908 12.5 4077 12.8 3900 28.7 3832 28.0 2127 11.4 1131 9.5

10-14.9 4361 14 4281 13.5 3951 29.0 3983 29.1 2605 14.0 1323 11.1

15+ 18801 60.2 19355 60.9 151 1.1 154 1.1 11239 60.4 7954 66.6

Missing 0 0.0 0 0.0 152 1.1 149 1.1 4 0.0 46 0.4

Years Smoked 10 or less 5472 14 5650 14.3 1 0.0 1 0.0 3410 11.7 2707 14.6

10.1-20 7682 19.7 7961 20.1 145 0.5 164 0.6 3774 13.0 2724 14.6

20.1-30 8008 20.5 8068 20.4 2673 10.1 2725 10.2 5123 17.6 3102 16.7

30.1-40 9473 24.3 9728 24.6 11567 43.6 11563 43.5 8175 28.1 5094 27.4

JAMA. Author manuscript; available in PMC 2016 June 09.

>40 8338 21.4 8199 20.7 12168 45.8 12151 45.7 8605 29.6 4970 26.7

Missing 207 0.5 216 0.5 0 0.0 0 0.0 4 0.0 46 0.2

a <10 9938 25.4 10197 25.7 6 0.0 7 0.0 2260 22.1 2768 29.2
Cigarettes per day

10-19 14111 36.1 14674 36.9 12654 47.7 12594 47.3 2619 25.7 2682 28.3

20-29 7916 20.2 7815 19.7 7216 27.2 7276 27.3 3516 34.5 2823 29.7

30-39 4346 11.1 4328 10.9 4811 18.1 4814 18.1 878 8.6 564 5.9

40-59 2255 5.8 2228 5.6 1666 6.3 1691 6.4 824 8.1 519 5.5

60-79 403 1 423 1.1 161 0.6 188 0.7 88 0.9 111 1.2

80+ 125 0.3 89 0.2 40 0.2 34 0.1 19 0.2 23 0.2

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PLCO control PLCO x-ray NLST x-ray NLST CT NHIS 1997-2001 NHIS 2010-2012

Categories N % N % N % N % N % N %

Sample Size 39,180 100.00 39,822 100.00 26,554 100.00 26,604 100.00 29,091 100.00 18,643 100.00
Missing 86 0.2 68 0.2 0 0.0 0 0.0 18887 64.9 9153 49.1
Katki et al.

Emphysema No 37172 95.7 37932 95.7 24447 92.3 24491 92.3 27379 94.1 17362 93.1

Yes 1676 4.3 1715 4.3 2031 7.7 2054 7.7 1712 5.9 1281 6.9

Missing 332 0.8 175 0.4 76 0.3 59 0.2 0 0.0 0 0.0

b None 34490 88.8 34978 88.6 22325 84.1 22348 84.0 28991 99.7 18214 97.7
Family History

1 3963 10.2 4092 10.4 3929 14.8 3958 14.9 91 0.3 414 2.2

2 406 1 420 1.1 300 1.1 298 1.1 9 0.0 15 0.1

NA 321 0.8 332 0.8 0 0.0 0 0.0 0 0.0 0 0.0

c Median, IQR 11.78 10.5,12.9 11.92 10.5,12.9 5.58 5.2,5.9 5.58 5.2,5.9 7.13 5.8,8.6 NA NA
Years of Follow-up

d e 1505 35.4 1604 37.2 964 58.7 1083 65.9 NA NA

Lung cancers number, rates

Lung cancer deaths e 1092 25.2 1120 25.4 442 30.9 354 24.6 684 31.6 NA
number, rates

PLCO = Prostate Lung Colorectal Ovarian Cancer Screening Trial

NLST - National Lung Screening Trial
NHIS – National Health Interview Survey, restricted to smokers age 50-80
CT – computed tomography
a
Information on cigarettes per day is not collected for former smokers in the NHIS.
b

JAMA. Author manuscript; available in PMC 2016 June 09.

Definition: No First Degree Relatives (FDRs) with lung cancer = 0, 1 FDR with lung cancer = 1, Two or more FDRs with lung cancer = 2.
c
Years of follow-up with cause of death data. For NLST, the median years of follow-up with lung cancer incidence data is 6.48 (IQR: 6.03,6.83) and 6.48 (IQR: 6.04,6.83) for the x-ray and CT groups
respectively.
d
Information on lung cancer incidence is not available on the NHIS 1997-2001. Neither incidence nor mortality follow-up data is available for NHIS 2010-2012.
e
Rates are expressed as events per 10,000 person-years.
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Table 3
Cause-specific hazards models for prediction of lung-cancer death, lung-cancer incidence, and competing mortality, based on data from the
control group of the PLCO Cancer Screening Trial
Katki et al.

Factor Coding Lung-Cancer Incidence Lung-Cancer Death Competing Mortality

Hazard 95% CI Hazard 95% CI Hazard 95% CI

Ratio Ratio Ratio

Age Log term 80.388 (35.904,179.985) 431.812 (185.0591,1007.5777) — —

Squared — — a — 1.001 (1.001,1.001)

—

Gender Binary 0.923 (0.829,1.027) 0.837 (0.736,0.950) 0.566 (0.534,0.599)

(female)

Race Categorical

White, 1.000 Reference 1.000 Reference 1.000 Reference

Non-
Hispanic

Black, 1.244 (1.006,1.537) 1.482 (1.176,1.869) 1.468 (1.330,1.621)

Non-
Hispanic

Hispanic 0.648 (0.401,1.0467) 0.687 (0.397,1.190) 1.001 (0827,1.211)

Asian or 0.673 (0.485,0.935) 0.657 (0.447,0.964) 0.849 (0.740,0.974)

Other

b Trend 0.931 (0.900,0.963) 0.908 (0.873,0.944) 0.957 (0.941,0.972)

Education

BMI≤18.5 Binary 1.063 ([Link]) 1.428 (0.899,2.268) 2.006 (1.628,2.472)

BMI
Log term 0.485 (0.343,0.686) 0.447 (0.296,0.675) — —

JAMA. Author manuscript; available in PMC 2016 June 09.

e — — — — 1.004 (1.003,1.004)
Squared

Pack-years Categorical

0-29.9 1.000 Reference 1.000 Reference 1.000 Reference

30-39.9 1.634 (1.328,2.011) 1.743 (1.354,2.244) 1.080 (0.985,1.185)

40-49.9 1.755 (1.445,2.131) 2.112 (1.679,2.657) 1.131 (1.029,1.244)

50+ 2.046 (1.608,2.603) 2.446 (1.861,3.214) 1.206 (1.079,1.349)

Quit years f 0.726 (0.676,0.779) 0.686 (0.640,0.735) 0.830 (0.802,0.859)

Log term

Years smoked Log term — — 1.395 (1.099,1.771) — —

Linear 1.024 (1.014,1.034) — — 1.002 (0.998,1.006)

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Factor Coding Lung-Cancer Incidence Lung-Cancer Death Competing Mortality

Hazard 95% CI Hazard 95% CI Hazard 95% CI

Ratio Ratio Ratio

>1 pack/day Binary 1.364 (1.154,1.613) 1.273 (1.054,1.539) 1.129 (1.043,1.221)

Katki et al.

Emphysema Binary 1.757 (1.503,2.054) 1.741 (1.450,2.090) 1.918 (1.754,2.096)

Lung-cancer d 1.519 (1.326,1.741) 1.525 (1.300,1.789) — —

Trend
c
family history

Abbreviations: BMI= Body mass index; CI= Confidence interval.

Note: For lung cancer incidence and death models, an increase of 1 year higher age results in the hazards increasing by HR{log(age+1)-log(age)}. If all other factors are the same, a 61 year old has
431.812{log(61)-log(60)}=1.11 times greater hazards of lung cancer death and a 80.388{log(61)-log(60)}=1.08 times greater hazards of lung cancer diagnosis than a 60 year old. For competing mortality
models, an increase of 1 year higher age results in hazards increasing by HR{(age+1)^2-age^2} If all other factors are the same, a 61 year old has 1.001{61^2-60^2}=1.13 times greater hazards of death
from other causes than a 60 year old.
a
“—“ means the specified risk factor, or parameterization of the risk factor, was not included.
b
<12 grade=1, high-school graduate=2, post high-school but no college=3, some College=4, Bachelor’s degree=5, graduate school=6.
c
FDR = First-degree relatives (siblings, parents, children) with history of lung cancer.
d
Definition: No FDRs with lung cancer = 0, 1 FDR with lung cancer = 1, Two or more FDRs with lung cancer = 2.
e
This is the square of (BMI-25). BMI is modeled as a binary category for being underweight (BMI≤18.5) and continuously for BMI>18.5.
f
This is natural logarithm of the sum of one and quit-years. All other log terms are natural logarithms.

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Table 4
Projected outcomes of an NLST-like CT lung screening program (3 yearly CT screens, 5-years follow-up) in the U.S., for different strategies
for selecting smokers
Katki et al.

Risk-based screening
strategies

All US ever- USPSTF- Fixed- Modeled

smokers eligible USPSTF Fixed-USPSTF
a b population d
ages 50-80 smokers effectiveness
c
Estimate Estimate size Estimate
(95% CIs) (95% CIs) Estimate (95% CIs)
(95% CIs)

Estimated number of eligible smokers 43,413,257 e e 12,101,749

(42,289.285- 9,018,130 9,018,693 (11,605,039-
44,537,230) (8,618,900- (8,645,982- 12,598,460)
9,417,361) 9,391,405)

Estimated 5-year Lung-cancer risk threshold - - 1.9% 1.7%

Estimated 5-year Lung-cancer death risk threshold - - 1.2% 0.9%

Estimated percentage of eligible smokers 100% 20.8% 20.8% 28%

(20.0-21.5) (20.1-21.5) (26.9-28.8)

Total estimated number of lung-cancer deaths in 403,161 227,891 273,127 305,808

the absence of screening (388,505- (215,313- (259,966- (291,966-
417,818) 240,457) 286,276) 319,588)

Estimated number of preventable lung-cancer 82,245 46,488 55,717 62,382

deaths from CT screening (79,255- (43,924- (53,033- (59,567-
85,235) 49,053) 58,400) 65,196)

Estimated percentage of preventable lung-cancer 100% 56.5% 67.7% 75.8%

deaths (55.0-58.1) (66.6-68.9) (74.9-76.8)

JAMA. Author manuscript; available in PMC 2016 June 09.

Estimated number needed to screen (NNS) to 528 194 74 194
prevent 1 lung-cancer death (513-543) (187-201) (157-166) (188-200)

Estimated number of false-positive screens per 294 133 116 134

prevented lung-cancer death (287-302) (128-137) (113-119) (131-138)

Estimated Number of extra diagnosed lung-cancers 0.96 0.93 0.91 0.92

per prevented lung-cancer death (0.95-0.96) (0.93-0.94) (0.91-0.92) (0.92-0.93)

Estimated mean 5-year lung-cancer risk 1.50% 3.9% 4.5% 3.8%

(1.42-1.50) (3.75-4.02) (4.42-4.67) (3.72-3.93)

Estimated mean 5-year lung-cancer death risk 0.9% 2.5% 3.0% 2.5%
(0.90-0.96) (2.43-2.62) (2.94-3.11) (2.45-2.60)

Abbreviations: NLST= National Lung Screening Trial; CT= computed tomography; US= United States; USPSTF= United States Preventive Services Task Force.
a
Estimates for US ever-smokers age 50-80 years indicate weighted estimates from the National Health Interview Survey (NHIS) 2010-2012
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b
Weighted estimated number of smokers age 55-80 years in the NHIS 2010-2012 who meet the USPSTF criteria for lung- cancer screening: at least 30 pack-years of smoking and no more than 15 years
since quitting smoking.
c
The fixed USPSTF population-size was selected by choosing the lung-cancer risk threshold such that the number screened matches the number of USPSTF-eligible smokers in the US.
d
The fixed USPSTF effectiveness population-size was selected by choosing the lung-cancer risk threshold such that the NNS matches the NNS based on screening all USPSTF-eligible smokers in the US.
e
Katki et al.

Totals are not exactly the same due to discreteness of weighted estimates of totals.

JAMA. Author manuscript; available in PMC 2016 June 09.

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 Author Manuscript Author Manuscript Author Manuscript Author Manuscript

Table 5
Characteristics of US ever-smokers ages 50-80 years under different selecting criteria for CT lung-cancer screening

All U.S. USPSTF- Risk-based Risk-based

Katki et al.

smokers ages eligible eligibility: eligibility:

a b fixed USPSTF modeled fixed
50-80 years smokers c USPSTF
N=43,413,257 e population size
N=9,018,130 d
% e effectiveness
% N=9,018,693 % N=12,101,749
%

Age, Years
50-54 23.8 0.0 1.4 3.5

55-59 20.3 29.5 9.5 12.5

60-64 19.9 28.2 21.0 21.9

65-69 15.1 20.5 23.7 22.4

70-74 11.1 12.6 21.7 19.2

75-80 9.8 9.3 22.7 20.6

Gender
Male 55.0 61.4 60.8 59.8

Female 45.0 38.6 39.2 40.2

Race
White, Non-Hispanic 80.2 85.0 82.4 82.0

Black, Non-Hispanic 9.8 7.7 12.8 12.9

Hispanic 7.1 4.7 3.2 3.6

JAMA. Author manuscript; available in PMC 2016 June 09.

Asian or Other 2.8 2.6 1.6 1.6

Education
Less than high-school 15.9 21.3 27.1 25.6

High-school graduate 27.2 29.6 32.7 32.2

Post-high-school, no 3.6 4.9 4.6 4.7

college

Some college 19.0 19.6 16.4 17.1

Bachelor’s degree 25.1 19.5 15.2 16.0

Graduate school 9.2 5.1 4.1 4.5

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All U.S. USPSTF- Risk-based Risk-based

smokers ages eligible eligibility: eligibility:
a b fixed USPSTF modeled fixed
50-80 years smokers c USPSTF
N=43,413,257 e population size
N=9,018,130 d
% e effectiveness
% N=9,018,693 %
N=12,101,749
Katki et al.

Body Mass Index, Kg/m2

<18 1.0 1.9 3.4 2.8

18-30 67.6 67.6 75.8 73.9

> 30 31.4 30.5 20.8 23.3

Emphysema

No 93.3 85.0 78.8 81.6

Yes 6.7 15.0 21.2 18.4

First-degree relatives with

lung-cancer
None 91.7 90.4 88.0 88.3

1 8.1 9.3 11.4 11.1

2 0.3 0.3 0.6 0.6

Smoking status
Former smoker 66.5 48.2 42.6 44.9

Current smoker 33.5 51.8 57.4 55.1

Duration of smoking, Years

<15 22.1 0.0 0.1 0.3

JAMA. Author manuscript; available in PMC 2016 June 09.

15-29 24.1 3.0 4.0 6.2

30-44 38.3 52.9 37.1 43.8

45+ 15.6 44.0 58.8 49.7

Time since quit, Years

<5 41.9 68.8 70.2 67.4

5-9 6.0 13.0 7.0 6.9

10-15 10.1 18.3 9.2 9.3

>15 42.0 0.0 13.6 16.3

Pack-years of smoking,
Years
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 Author Manuscript Author Manuscript Author Manuscript Author Manuscript

All U.S. USPSTF- Risk-based Risk-based

smokers ages eligible eligibility: eligibility:
a b fixed USPSTF modeled fixed
50-80 years smokers c USPSTF
N=43,413,257 e population size
N=9,018,130 d
% e effectiveness
% N=9,018,693 %
N=12,101,749
Katki et al.

%
<15 42.2 0.0 10.3 12.7

15-29 23.9 0.0 11.2 13.4

30-45 17.7 44.1 24.7 27.4

>45 16.2 55.9 53.8 46.5

f
Cigarettes per day

<10 25.0 0.0 13.1 15.2

10-19 24.9 11.6 17.1 18.0

20-29 32.9 57.4 39.5 38.1

30-39 6.6 13.7 12.8 11.8

40-49 7.2 12.5 12.0 11.4

50+ 3.5 4.9 5.6 5.5

Note: Percentages are column percentages for each factor.

Abbreviations: NLST= National Lung Screening Trial; CT= computed tomography; US= United States; USPSTF= United States Preventive Services Task Force.
a
Estimates for US ever-smokers age 50-80 years indicate weighted estimates from the National Health Interview Survey (NHIS) 2010-2012
b
Weighted estimated number of smokers age 55-80 years in the NHIS 2010-2012 who meet the USPSTF criteria for lung-cancer screening: at least 30 pack-years of smoking and no more than 15 years
since quitting smoking.

JAMA. Author manuscript; available in PMC 2016 June 09.

c
The fixed USPSTF population-size was selected by choosing the lung-cancer risk threshold such that the number screened matches the number of USPSTF-eligible smokers in the US.
d
The modeled fixed USPSTF effectiveness population-size was selected by choosing the lung-cancer risk threshold such that the NNS matches the NNS based on screening all USPSTF-eligible smokers in
the US.
e
Totals are not exactly the same due to discreteness of weighted estimates of totals.
f
20 cigarettes = 1 pack of cigarettes.
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