Cost-Effectiveness Analyses of Lung Cancer

Screening Strategies Using Low-Dose

Computed Tomography: a Systematic
Review

Adam J. N. Raymakers, John Mayo,

Stephen Lam, J. Mark FitzGerald, David
G. T. Whitehurst & Larry D. Lynd

Applied Health Economics and Health

Policy

ISSN 1175-5652

Appl Health Econ Health Policy

DOI 10.1007/s40258-016-0226-5

1 23
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 Author's personal copy
Appl Health Econ Health Policy
DOI 10.1007/s40258-016-0226-5

SYSTEMATIC REVIEW

Cost-Effectiveness Analyses of Lung Cancer Screening Strategies

Using Low-Dose Computed Tomography: a Systematic Review
Adam J. N. Raymakers1,7 • John Mayo2 • Stephen Lam3,4 • J. Mark FitzGerald4 •

David G. T. Whitehurst5,6 • Larry D. Lynd1,7

 Springer International Publishing Switzerland 2016

Abstract
Background Lung cancer screening with low-dose com-
puted tomography (LDCT) has been shown to deliver appre-
ciable reductions in mortality in high-risk patients. However,
in an era of constrained medical resources, the cost-effec-
tiveness of such a program needs to be demonstrated.
Objective The aim of this study was to systematically
review the literature analyzing the cost-effectiveness of
lung cancer screening using LDCT.
Methods We searched MEDLINE, EMBASE, EBM
Reviews—Health Technology Assessment, the National
Health Service Economic Evaluation Database (NHS-EED),
and the Cochrane Database of Systematic Reviews. Due to
technological progress in CT, we limited our search to
studies published between January 2000 and December
& Adam J. N. Raymakers
raymaker@mail.ubc.ca
1
Collaboration for Outcomes Research and Evaluation
(CORE), Faculty of Pharmaceutical Sciences, University of
British Columbia, Room 4102–2405 Wesbrook Mall,
Vancouver, BC, Canada
2
Department of Radiology, University of British Columbia,
Vancouver, BC, Canada
3
Department of Integrative Oncology, British Columbia
Cancer Agency, Vancouver, BC, Canada
4
Division of Respiratory Medicine, Faculty of Medicine,
University of British Columbia, Vancouver, BC, Canada
5
Faculty of Health Sciences, Simon Fraser University,
Burnaby, BC, Canada
6
Centre for Clinical Epidemiology and Evaluation, Vancouver
Coastal Health Research Institute, Vancouver, BC, Canada
7
Centre for Health Evaluation and Outcomes Sciences
(CHEOS), St Paul’s Hospital, Vancouver, BC, Canada
2014. Our search returned 393 unique results. After remov-
ing studies that did not meet our inclusion criteria, 13 studies
remained. Costs are presented in 2014 US dollars (US$).
Results The results from the economic evaluations iden-
tified in this review were varied. All identified studies
reported outcomes using either additional survival (life-
years gained) or quality-adjusted life-years (QALYs
gained). Results ranged from US$18,452 to US$66,480 per
LYG and US$27,756 to US$243,077 per QALY gained for
repeated screening. The results of cost-effectiveness anal-
yses were sensitive to several key model parameters,
including the prevalence of lung cancer, cost of LDCT for
screening, the proportion of lung cancer detected as
localized disease, lead time bias, and, if included, the
characteristics of a smoking cessation program.
Conclusions The cost-effectiveness of a lung cancer
screening program using LDCT remains to be conclusively
resolved. It is expected that its cost-effectiveness will lar-
gely depend on identifying an appropriate group of high-
risk subjects.
Key Points for Decision Makers
Results from cost-effectiveness analyses of lung
cancer screening with low-dose computed
tomography are varied.
Smoking cessation programs appear to be an
important component of a lung cancer screening
strategy.
Improvements in methods to properly identify high-
risk patients will impact cost-effectiveness of
screening strategies.
 Author's personal copy
1 Background
Lung cancer is the most common cause of cancer death
worldwide, with an estimated 1.8 million new cases and
1.6 million deaths in 2012 [1]. Over the past four decades,
clinical interventions have had only a minimal effect on
reducing death from lung cancer [2]. The 5-year survival
rate for patients with lung cancer is currently less than
18 % because most cases are not found until patients
become symptomatic with advanced and incurable disease
[3]. The National Lung Screening Trial (NLST) in the US
recently showed that lung cancer screening with low-dose
computed tomography (LDCT) in high-risk current and
former smokers can reduce death from lung cancer by
20 % compared with chest X-ray, which provides an
alternative strategy to improve lung cancer diagnoses and
outcomes [4]. The recommendation by the US Preventive
Services Task Force (USPSTF) to screen high-risk smokers
with LDCT [5, 6] and the recent decision by the Centers for
Medicare and Medicaid Services to fund LDCT screening
under the Medicare program [7] means that LDCT
screening will be implemented at the population level in
the US and likely in other countries.
A recent US study estimated that a lung cancer
screening program could potentially increase health care
expenditures by US$1.4 to US$2.1 billion depending on the
program uptake rate [8]. Given limited healthcare resour-
ces, careful analysis is required prior to implementing
LDCT screening programs. Economic evaluation is a tool
that can be used to simultaneously analyze both the costs
and consequences of health programs, facilitating com-
parison of alternative programs that might not otherwise be
directly comparable. The results of these analyses allow
decision makers to make informed choices given scarce
healthcare resources [9]. The simultaneous evaluation of
costs and outcomes is particularly relevant for screening
studies. Screening for any disease can be expensive and the
potential benefits tend to be derived from earlier identifi-
cation and treatment initiation, which can generate addi-
tional associated costs. Therefore, in order to properly
assess a screening program, consequences (i.e. benefits)
should be shown in terms of length and/or quality of life
that may be gained from the screening program, as opposed
to costs averted.
There are several key factors in LDCT screening for
lung cancer that can impact estimates of cost-effectiveness,
such as lead-time, overdiagnosis, and incidental findings.
Lead time is particularly important for lung cancer
screening; it is the time difference between screening-de-
tected lung cancer and symptomatic presentation of lung
cancer. A screening strategy that generates substantial lead
time could potentially generate significant therapeutic
A. J. N. Raymakers et al.
benefits that will also impact cost-effectiveness estimates.
Overdiagnosis is a concern with LDCT screening due to its
high sensitivity for early-stage lung cancer. Accordingly, a
potential drawback of using LDCT to image the lungs is
that more surgeries than clinically necessary may be
undertaken, which could be associated with increased
costs, patient anxiety, and potential adverse events. The
alternative diagnostic capacity of LDCT and non-lung
cancer health risks associated with smoking can lead to the
detection of incidental findings in screened subjects.
Detection of non-lung cancer changes such as coronary
artery calcifications or emphysema has advantages and
disadvantages in that it might improve outcomes by iden-
tifying these diseases but with the potential for overtreat-
ment, complications, and increase in overall costs.
The objective of this study was to systematically review
and critically evaluate published studies that explore the
cost-effectiveness of lung cancer screening using LDCT.
We highlight the complexity of LDCT screening for lung
cancer from an economic evaluation perspective and offer
suggestions to improve the quality of future studies.
2 Methods
A search strategy was developed using the following
databases: MEDLINE, Excerpta Medica Database
(EMBASE), the National Health Service (NHS) Centre for
Reviews and Dissemination Health Technology Assess-
ment database, National Health Service Economic Evalu-
ation Database (NHS-EED), and the Cochrane Database of
Systematic Reviews. The search included the following
subject headings (and included all relevant subheadings):
‘cost-benefit analysis’, ‘health care costs’, ‘quality-adjusted
life years’, ‘lung neoplasms’, ‘mass screening’, ‘models
(economic)’, ‘tomography (X-ray computed)’, and ‘to-
mography (spiral computed)’. Additional keywords inclu-
ded in the search were ‘cost-effectiveness’, ‘lung cancer’,
‘economic evaluation’, and ‘computed tomography’. Two
authors (AR and DW) independently reviewed and com-
pared the results of the search. Inconsistencies in the results
were resolved through discussion. Any further uncertainty
as to inclusion was discussed within the study team. Ref-
erences provided by the included studies were also sear-
ched using the same study selection criteria (Fig. 1). The
search strategy is detailed in the ‘‘Appendix’’.
2.1 Study Selection
Articles were chosen for inclusion if the authors conducted
a cost-effectiveness analysis evaluating the use of LDCT as
a screening tool for lung cancer. Due to substantial
 Author's personal copy
Cost-Effectiveness of Lung Cancer Screening

Fig. 1 Study selection process,

with reasons for exclusion.
CRD-HTA Centre for Reviews
and Dissemination Health
Technology Assessment, NHS-
EED National Health Service
Economic Evaluation Database

advances in CT, primarily the introduction of multidetector
row technology, the search was limited to include studies
published between January 2000 and December 2014.
2.2 Study Abstraction
The following parameters were extracted from each study
and entered into a standardized data abstraction form:
LDCT cost, LDCT sensitivity and specificity, key model
parameters (perspective of the analysis, discount rate,
currency year, study location, and patient population),
whether sensitivity analysis was performed, model char-
acteristics specific to lung cancer screening (i.e. consider-
ation of lead time bias and incidental findings analysis),
and the calculated incremental cost-effectiveness ratio
(ICER). To facilitate comparison between published stud-
ies all costs were adjusted to 2014 US dollars [10, 11].
We followed the criteria proposed by Drummond et al.
(chapter 2) [9] for assessing economic evaluations. These
criteria assess cost-effectiveness analyses in terms of their
attributes, including whether or not comparators were well-
described, whether the data used to populate the model
were from reliable sources, whether differential timing was
allowed for, if ICERs were calculated, and if sensitivity
analysis was performed. This review did not explicitly use
a quality assessment metric but used these established
criteria to facilitate consideration of key study components.
Such an approach has been used in previous review studies
[12].
3 Results
The search strategy yielded 393 unique results and 13
studies met the inclusion criteria [13–25]. Ten of the
included studies were from the US, and one each from
Australia, Israel, and Japan. The process by which studies
were included (along with reasons for exclusion) is out-
lined in Fig. 1.
3.1 At-Risk Patient Population
The risk of lung cancer in the population to be screened
will be a critical component impacting the cost-effective-
ness of such a program. Studies included in this review
focused predominantly on high-risk groups (defined as
 Author's personal copy
being either 50 or 60 years of age or older with a signifi-
cant smoking history (i.e. C20–30 pack-years)). Of the 13
studies identified in this review, ten [14–20, 22, 23, 25]
used similar definitions for their patient population, which
aligned closely with those used in NLST and Early Lung
Cancer Action Project (ELCAP) studies (Table 1). The
remaining three studies screened unique and typically
younger populations [13, 21, 24]. Beinfeld et al. [13] did
not focus on a high-risk population but rather evaluated the
cost-effectiveness of a single whole-body screening for
eight malignancies (including lung cancer) in subjects
greater than 50 years of age. The youngest age included in
a screening program amongst included studies was
observed in Okamoto et al. [21], who screened individuals
40 years of age and older.
3.2 Modeling Approach
The modeling approach in all studies was similar, typically
using decision analytic modeling to evaluate an LDCT-
based screening program versus no screening. The majority
of studies evaluated annual screening [14–18, 20, 22, 23,
25], while four evaluated a one-time screening program
[13, 19, 21, 24]. All but one study [21] performed sensi-
tivity analysis on the model structure and/or key parame-
ters, and only one study conducted probabilistic sensitivity
analysis [24]. Only ten of the studies reported the per-
spective from which the analysis was conducted [13–17,
20, 22–25]. Lung cancer treatment costs were associated
with the stage at which the cancer was diagnosed. Lung
cancer detected by LDCT screening was typically associ-
ated with a ‘stage-shift’, meaning that the distribution of
LDCT-discovered lung cancers was ‘shifted’ toward an
earlier stage of lung cancer. For example, in the study by
Mahadevia et al. [16], the authors employed a 50 % stage
shift whereby the distribution of lung cancer cases (be-
tween localized and advanced disease) in the screened
group would be 50 % toward earlier disease compared with
the unscreened group.
Approximately half of the studies identified in this
review made some allowance for lead-time bias. In anal-
yses where lead-time was considered, it was assumed to be
either 1 year [17], 2 years [24, 25], or 3 years [23]. The
variation in the estimate for this model parameter reflects
the uncertainty in what the actual lead-time for lung cancer
is, and how it may be dependent on the patient population,
lung cancer histology, and the subjects’ response to
treatment.
A major consideration in the cost-effectiveness of lung
cancer screening is smoking cessation. Four studies inclu-
ded smoking cessation programs with annual screening
[20, 22, 23, 25]. A smoking cessation program coupled
with a lung cancer screening strategy has the potential to
A. J. N. Raymakers et al.
decrease smoking rates among those undergoing screening
(high-risk patients), thereby reducing mortality from lung
cancer and other diseases [26]. The potential for this added
benefit (and cost) was considered by McMahon et al. [20],
who included a smoking cessation program costing
US$352 per person. This program increased smoking ces-
sation by 4–30 % depending on the patient population,
above a background smoking cessation rate of 3 % [20].
Villanti et al. [25] used a background rate of 2.5 % and an
increase depending on the intensity of the smoking cessa-
tion program (1.5–3.04 times the background rate), and
included costs for corresponding smoking cessation inter-
ventions (counselling, nicotine replacement therapy,
pharmacotherapy).
3.3 Low-Dose Computed Tomography Attributes
The sensitivity and specificity associated with LDCT is an
important component of the screening program and will
influence cost-effectiveness estimation. Reported sensitiv-
ities of LDCT to detect nodules were dependent on the
nodule size and ranged from 0.63 [20] to 0.94 [16, 27]
(Table 2). The specificity of LDCT was reported less fre-
quently [13, 16, 17], ranging from 0.79 [13] to 0.97 [17]. In
the study by Shmueli et al. [24], no allowance was made
for false negative results in screening, which the authors
justify by stating that there is ‘‘… no practical observa-
tional way to confirm false negative cases’’ (p. 923).
Depending on the location of the malignant nodule (e.g.
perihilar, vessel bifurcation), it is reasonable to expect that
LDCT will occasionally be falsely negative. In this cir-
cumstance, subjects would be diagnosed when symptoms
present, and the costs associated with screening will be
purely additional. Therefore, failure to account for false
negative cases would overestimate the benefit conferred by
LDCT screening. The extent to which this scenario exists
reflects an unquantified issue that will impact cost-effec-
tiveness estimations.
3.4 Outcome Measures
The studies identified in this review reported outcomes in
terms of life-years gained or quality-adjusted life-years
(QALYs) gained. More recent studies tended toward using
QALYs as an outcome measure, consistent with most
guidelines [28, 29]. Prior to the study by Black et al. [14],
no study contained an original estimate of utility values
elicited from patients, nor did any use patients’ responses
to preference-based utility instruments for patients under-
going lung cancer screening—all used previously pub-
lished utility estimates. Black et al. [14] produced utility
weights from a subset of 11,696 of the NLST patients who
answered the Short-Form 36 (SF-36). Utility weights for
Table 1 Summary of identified studies
Author Year Country Patient population Screening Modelling approach Time Discount Indirect Perspective Sensitivity
frequency horizon rate costs (reported) analysis

Beinfeld 2002 US 50? year old males One time Decision tree Lifetime Not No ‘Quasai’ Yes
[13] applied societal
Black [14] 2014 US 55–74 years and a smoking history of 30? pack years Annual Trial based Lifetime 3% Yes Societal Yes
(NLST) economic
evaluation
Cost-Effectiveness of Lung Cancer Screening

Chirikos 2002 US 60?, smoking history of 10? pack years (ELCAP) Annual Not reported 15 years 7.5 % No National Yes
[15] (costs payer
only)
Mahadevia 2003 US Current, quitting, and former heavy smokers aged 60 Annual Markov model 20 years 3% No Societal Yes
[16]
Manser 2005 Australia Males 60–64 years and smoking history of 40 Annual Markov model 15 years 3% No 3rd party Yes
[17] cigarettes a day for 40 years (high risk) payer
Marshall 2001 US 60–74 years (ELCAP) Annual Decision tree 5 years 3% No Not reported Yes
[18]
Marshall 2001 US 60–74 years; high and low risk One time Decision Tree 5 years 3% No Not reported Yes
[19]
McMahon 2011 US 50–74 years and 20? pack years of smoking history Annual Patient-level Lifetime 3% Yes Societal Yes
[20] simulation model
Okamato 2000 Japan Mass screening; 40? years and smoking index greater One time Deterministic Lifetime Not No Not reported No
[21] than 600 mathematical reported
Author's personal copy

model
Pyenson 2012 US Smokers and former smokers aged 50–64 with Annual Actuarial analysis 15 years Not No Commercial Yes
[22] minimum of 30 pack years applied payer
Pyenson 2014 US 55–80 years and a smoking history of 30? pack years Annual Actuarial analysis Lifetime Not No Medicare Yes
[23] (and smoked within past 15 years) applied
Shmueli 2013 Israel Moderate to heavy smokers aged 45? One time decision tree Lifetime 3% No Health Yes
[24] system
Villantini 2013 US 50–64 years and 30? pack years Annual Actuarial analysis 15 years Not No Commercial Yes
[25] applied payer
NLST National Lung Cancer Screening Trial, ELCAP Early Lung Cancer Action Project, US United States
 Author's personal copy
A. J. N. Raymakers et al.

Table 2 Reported sensitivity, specificity, and costs of CT

Author CT sensitivity/specificity Currency (year) CT cost [2014 US$]

Repeated screening
Black [14] 0.94; 0.73a USD (2009) 285 [314.49]
Chirikos [15] NR USD (2000) 291 [400.06]
-416 [571.91]b
Mahadevia [16] 0.94; 0.79 USD (2001) 300 [401.02]
Manser [17] 0.86; 0.97 AUSD (2002) 280 [275.69]
Marshall [18] NR USD (1999) 150 [213.15]
McMahon [20] 0.63–1 (depending on nodule size); NR USD (2006) 283 [332.32]
Pyenson [22] NR USD (2012) 247 [254.68]
Pyenson [23] NR USD (2014) 241
Villantini [25] NR USD (2012) 210 [216.53]
One-time screening
Beinfeld [13] 0.83; 0.83 USD (2001) 900 [1203.06]e
c
Marshall [19] NR USD (2001) 150 [200.51]
Okamato [21] 0.90; NR USD/Japanese Yen (NR) 30 [42.63]
Shmueli [24] NRd USD (2011) 74 [77.88]
a
Not reported but assumed based on the results of the NLST (27)
b
Varied based on usage of contrast material
c
Reported a 100 % cancer detection rate
d
No allowance was made for false negative results
e
Whole body scan

two studies [20, 25] were obtained from Hanmer et al. [30],
who reported utility scores based on the US Medication
Expenditure Panel Survey (MEPS). This survey, conducted
in 2001, collected SF-12 (version 1) and EQ-5D (a pref-
erence-based measure of health-related quality of life)
scores from a representative sample of the non-institu-
tionalized population over the age of 18 years. Three
studies [16–18] used a systematic review by Earle et al.
[31] as a source for utility values. Shmueli et al. [24] used
utility values obtained from a panel of family physicians
who were asked to consider a series of hypothetical sce-
narios and, for each scenario, complete the EQ-5D-3L
instrument.
3.5 Model Results
Cost-effectiveness estimates varied substantially between
studies. For life-years gained (i.e. using survival as the
measure of outcome), ICERs ranged from US$8441 [19] to
US$201,847 [13] per life-year gained for one-time screen-
ing, and US$18,452 [23] and US$66,480 [15] for repeated
screening. For studies using QALYs as the outcome mea-
sure, results ranged from US$27,756 [18] to US$243,077
[20] per QALY gained (Table 3). For one-time screening,
only one study reported an ICER in terms of QALYs
(US$1541/QALY) [24]. One study did not report an incre-
mental ratio [21]. In instances where similar parameter
values were used, the difference in cost-effectiveness esti-
mates relates to the modeling approach taken by the authors.
For example, McMahon et al. [20] and Villanti et al. [25] are
US-based studies with substantially different ICER esti-
mates (US$169,097 and US$29,118 per QALY, respec-
tively). Both studies used utility weights from the same
study [30] and LDCT costs that were not remarkably dif-
ferent (US$332 and US$217, respectively). In a sensitivity
analysis conducted by Villanti et al. [25], the cost of LDCT
was increased 150 %, and the resulting ICER only increased
to US$45,989 per QALY gained (from a base-case estimate
of US$29,118 per QALY). Two aspects of this study are
worth noting; first, the time horizon used in this analysis was
15 years, not lifetime, and, second, the population was
males and females 50–64 years of age. In their analysis,
McMahon et al. [20] used a lifetime time horizon with
people aged 50–74 years. It should be noted that all studies
which reported ICERs in excess of US$100,000 per QALY
or life-year gained were completed before or did not
incorporate the results of the NLST [13, 16, 17, 20].
Overall, the model results (Table 3) appeared to be
particularly sensitive to the prevalence of lung cancer, the
cost of the LDCT screening test, the proportion of lung
cancer detected as localized disease, and lead time bias. In
addition, for those studies that included a smoking cessa-
tion program, the model results were particularly sensitive
to the characteristics of this program.
 Author's personal copy
Cost-Effectiveness of Lung Cancer Screening

Table 3 Results of identified economic evaluations

Author Currency (year) Outcome metric DCost [2014 US$] DEffect ICER [2014 US$]

Repeated screening
Black [14] USD (2009) LY and QALY 1631 [1799.77] 0.0316 LY and 52000 [57380.69] per LY and 81000
0.0201 QALYs [89381.46] per QALY
Chirikos [15] USD (2000) LY 76500 [105170.25] 1.582 48357 [66479.97]
Mahadevia [16] USD (2001) QALY 4600 [6148.99] 0.039 116300 [155462.54]
Manser [17] AUSD (2002) QALY 1649 [1623.64] 0.016a 105090 [103473.51]
a
Marshall [18] USD (1999) QALY 960 [1364.15] 0.0491a 19533 [27756.11]
McMahon [20] USD (2006) QALY 1778–3637 0.009–0.022 144000–207000 [169097.
[2087.88–4270.88] 26–243077.31]
Pyenson [22] USD (2012) LY NR NR 18862 [19448.76]
Pyenson [23] USD (2014) LY 16053a 0.87a 18452
a a
Villantini [25] USD (2012) QALY 1546 [1594.09] 0.055 28240 [29118.50]
One-time screening
Beinfeld [13] USD (2001) LY 2513 [3359.22] 0.016 151000 [201847.32]
Marshall [19] USD (1999) LY 260a [369.46] 0.0438a 5940 [8440.65]
Okamato [21] USD/Japanese Life saved NR NR NRb
Yen (NR)
Shmueli [24] USD (2011) QALY 86 [90.51] 0.0591 1464 [1540.78]
USD United States Dollars, LY life years, LYG life years gained, QALY quality-adjusted life-years, AUSD Australian dollars, NR not reported
a
Calculated based on results reported in the study
b
Reported only graphically

4 Discussion screening program, including the frequency of screening,

This systematic review reports on the published economic
evaluations of lung cancer screening incorporating LDCT,
and is the first review to do so after publication of the
results of the NLST. In addition, we sought to identify the
key components of an economic evaluation for lung cancer
screening and provide insight into areas of improvement
for future studies. The results of this review suggest that
whether LDCT screening for lung cancer is cost effective
remains unclear and published cost-effectiveness estimates
are heavily contingent on the modeling approach and val-
ues of several key parameters. The identified analyses were
particularly sensitive to the at-risk population to be
screened, the cost of the LDCT screening test, the pro-
portion of lung cancer detected as localized disease, lead-
time bias, and, if included, the characteristics of a smoking
cessation program. This review reiterates the importance of
economic evaluation prior to the implementation of pop-
ulation-based screening programs.
A previously conducted review by Black et al. [33]
reported that in the absence of a proper trial to evaluate
LDCT as a method for lung cancer screening, no decision
about adoption could be made due to the paucity of good-
quality data demonstrating the efficacy for LDCT in this
capacity. The report suggested that several factors would
be very important to the cost-effectiveness of a lung cancer
patients’ age, and lung cancer risk. Most of these issues
have been addressed by subsequent cost-effectiveness
analyses, which are described in the current paper,
although patients’ age and the definition of ‘high risk’
varied across studies.
Multiple identified analyses had issues with model
transparency and proper use and understanding of termi-
nology used in economic evaluation. For example, earlier
studies did not present model parameters as clearly as later
studies [15, 18, 19, 21], and sensitivity and specificity
values were absent from several studies [15, 18, 19, 22–
24]. Clarity regarding the cost-year, discount rate, and
perspective of the analysis also varied. Several studies
claimed to conduct their analysis from a ‘societal’ per-
spective but it was unclear what societal costs were
included [13, 16, 20]. In addition, Pyenson et al. [23] did
not discount costs or outcomes, stating that 2014 costs were
used throughout their analysis, precluding the necessity of
discounting future costs. This reflects a lack of under-
standing regarding the concept of time preference and why
discounting is important in the estimation of cost-effec-
tiveness. Only two studies included indirect costs; one
estimated lost wages for patients receiving a lung cancer
diagnosis [25], and the other included losses due to travel
time associated with screening for both patients and care-
givers [14]. While sensitivity analyses were conducted in
 Author's personal copy
most studies, probabilistic sensitivity analysis was only
performed in one study [24]. This is a major limitation
given the uncertainty surrounding many model parameters
and the insights that could be gained through the use of
probabilistic methods to inform future research [34]. Two
studies were comprehensive in that while they modeled the
benefits of LDCT screening, the potential harm (in terms of
aggregate radiation) was also taken into account [17, 20].
Manser [17] highlighted a potential ‘worst-case’ scenario,
where under the most pessimistic of published conditions,
for example an LDCT sensitivity of 0.65 and cost of
US$552, LDCT screening could result in a loss of life-
years in their hypothetical cohort, pointing to the impor-
tance of a programmatic approach to screening imple-
mentation versus ad hoc or opportunistic screening.
Only one study incorporated the possibility of incidental
findings affecting cost-effectiveness estimates in the base-
case analysis. Black et al. [14] assigned a cost of US$500
for a patient with a clinically significant incidental finding.
It is possible that there could be additional benefits from
non-lung cancer findings in annual screenings for patients
who would be at high risk for other diseases given their age
and smoking history. For example, in their study of 4073
patients undergoing lung cancer screening, Kucharzyk
et al. [35] found that 19 % of patients had ‘actionable’
incidental findings. In addition, given the associated risk of
chronic obstructive pulmonary disease (COPD) in smokers,
as technology advances LDCT could be used as a diag-
nostic tool for COPD, which suffers from underdiagnosis,
particularly in milder disease states [36]. Villanti et al. [25]
report that annual scans may also be beneficial for
improving risk identification for coronary heart disease
(CHD) [37].
Several factors may have implications for future cost-
effectiveness analyses. Technological advances in multi-
detector CT scanner technology will likely decrease
examination time and radiation dose, which has the
potential to improve the cost-effectiveness of LDCT
screening programs. In addition to technological advances,
improved selection criteria for patients can have a signifi-
cant impact on cost-effectiveness. In the NLST, the 20 %
of participants with the lowest risk (using age 55–74 years
and C30 pack-years as inclusion criteria) accounted for
only 1 % of prevented lung cancer deaths [4]. Tammemägi
et al. [38] compared the NLST selection criteria with a
modified version of the Prostate, Lung, Colorectal and
Ovarian (PLCO) Cancer Screening Trial criteria
(PLCOm2012). Compared with NLST, they found the
PLCOm2012 showed increased sensitivity and positive pre-
dictive value. More recently, Tammemägi et al. [39] found
that the PLCOm2012 risk model for selecting patients for
screening had greater sensitivity, specificity, and positive
predictive value than the USPSTF criteria. Moreover, the
A. J. N. Raymakers et al.
PLCOm2012 model selected fewer patients for screening,
yet identified 12.4 % more lung cancers [39]. This selec-
tion method for screening could increase both efficiency of
LDCT screening and cost-effectiveness. The use of more
sophisticated risk prediction models to select smokers for
LDCT screening versus NLST or USPSTF criteria should
be validated in a prospective trial to compare these
parameters (number of lung cancers identified, differences
in the number needed to screen to detect one lung cancer,
and the positive predictive value). The evidence for the
appropriate tumour size and growth rate that are predictive
of lung cancer has also been improving [40]. Finally, the
prevalence of lung cancer in the screened population and
the frequency of follow-up of screened subjects can greatly
influence the cost of the program. Reduction in the fre-
quency of follow-up LDCT scans using larger nodule size
to define a positive screen has also been proposed [41] but
prospective cost-effectiveness analyses are needed [42].
Lung cancer screening offers an excellent opportunity
for physicians to promote smoking cessation in their
patients [26]. Smokers who participated in lung cancer
screening had a three- to fivefold higher smoking cessation
rate compared with smokers in the general population,
which is generally between 2 and 3 % [43–45]. The ben-
efits of smoking cessation that could be combined with a
lung cancer screening program need to be included in
future cost-effectiveness analyses, or at a minimum as a
sensitivity analyses.
The NLST showed that lung cancer screening may
confer a benefit of approximately 20 % in reduced lung
cancer mortality in a high-risk patient population. While
the results of the NLST should have a substantial impact on
the cost-effectiveness of a lung cancer screening program,
clinical effectiveness does not (necessarily) equate with
cost-effectiveness and, in an era of constrained healthcare
resources and emerging expensive medical technologies,
economic evaluation can help us make efficient resource
allocation decisions. The studies identified in this review
highlight that while there may be survival and quality-of-
life gains that accrue from lung cancer screening (partic-
ularly in high-risk populations), there is considerable
variation in ICERs. Studies conducted prior to the com-
pletion and availability of results from the NLST typically
had higher ICERs, whereas more recent results show more
favourable ICERs, due to both lower incremental costs and
better effects.
4.1 Limitations
This systematic review only included studies that were
published from the year 2000 onward since, for techno-
logical reasons, LDCT was inadequate for screening prior
to that time. In addition, our review was limited to studies
 Author's personal copy
Cost-Effectiveness of Lung Cancer Screening
published in English as personnel to review non-English
results were not available. However, our search returned
very few non-English results (Fig. 1), therefore we feel that
our results are robust. Lastly, without access to the com-
plete models from identified studies it is difficult to fully
comprehend the discrepancy in the magnitude of model
results (ICERs) beyond stated model parameters and
assumptions.
5 Conclusions
Evidence from recent trials has shown that significant
reductions in mortality can be achieved with screening a
high-risk population for lung cancer with LDCT; however,
whether or not such a program is cost effective is still
contentious. The impact of incidental findings, only con-
sidered by one study in this review, will undoubtedly affect
cost-effectiveness estimates in this population with ele-
vated cardiovascular, COPD, and cancer risk. The cost-
effectiveness of a lung cancer screening program might
also be enhanced with improved risk stratification,
knowledge of nodule size predictive of lung cancer,
advances of CT technology, and inclusion of a smoking
cessation program alongside a screening strategy.
Author contributions Adam Raymakers generated the original
idea for this study, conducted the systematic review, and drafted and
submitted the manuscript. John Mayo and Mark FitzGerald helped
with the conceptualization of the study and editing of the manuscript.
Both authors added valuable clinical input to the study. Stephen Lam
reviewed and edited the manuscript and provided critical insight into
the subject area. David Whitehurst was the second reviewer in the
systematic review, and assisted with drafting and editing the manu-
script, and manuscript submission. Larry Lynd helped with concep-
tualization of the study, and drafting and editing the manuscript. All
authors approved the final version of the manuscript.
Compliance with Ethical Standards
Conflicts of interest Adam Raymakers, John Mayo, Stephen Lam,
Mark FitzGerald, David Whitehurst, and Larry Lynd declare no
competing interests with this study.
Funding No specific funding was used for this study.
Appendix: EMBASE search strategy, searched
via OvidSP
1. lung cancer/
2. mass screening/
or screening test/
or cancer screening /
or screening
3. economic evaluation.mp or economics/
or ‘‘health care cost’’/
or ‘‘cost benefit analysis’’ /
or ‘‘cost-effectiveness analysis’’/
or economic aspect/
or economic evaluation/
or health economics/
4. computed tomography.mp. or computer asssisted
tomography /
5. spiral computer assisted tomography/
6. 4 or 5/
7. 1, 2, and 3/
8. 6 and 7/
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