REVIEW

CURRENT
OPINION Management of the solitary pulmonary nodule
Faria Nasim and David E. Ost

Purpose of review
We review the categorization and management of solitary pulmonary nodules.
Recent findings
The National Comprehensive Cancer Network guidelines were updated in 2018 and the revised Fleischner
Society guidelines were published in 2017. The revised Fleischner Society guidelines published in 2017
have less frequent follow-up recommendations for incidentally detected pulmonary nodules with longer
intervals between subsequent CT scans. The updated 2018 version of National Comprehensive Cancer
Network lung cancer screening guidelines provide recommendations for screen-detected nodules based on
a patient’s risk of cancer. New molecular assays may be of use in patients with a pretest probability of
malignancy less than 50%. When these tests indicate low risk, a strategy of follow-up CT imaging may be
feasible, avoiding unnecessary invasive testing. However, further clinical utility studies are needed in this
area.
Summary
Management options for pulmonary nodules include watchful waiting with follow-up CT imaging, PET
imaging, or further invasive testing based on probability of malignancy. With a low estimated risk of
malignancy in an incidentally detected solitary pulmonary nodule, longer intervals between follow-up CT
scans are recommended for patients. For patients at high risk for malignancy or those with nodules of at
least 8 mm, either incidentally, screen detected, or symptom driven, a diagnostic biopsy is necessary to
establish the cause of a solitary pulmonary nodule.
Keywords
lung cancer screening, lung nodule tissue diagnosis, screen versus incidental pulmonary nodule, solitary
pulmonary nodule

INTRODUCTION cancer in SPNs ranges from 10% to 70%, with an

The finding of a solitary pulmonary nodule (SPN) is
a common clinical problem. In this review article,
we start with defining the SPN. We then describe
three clinical contexts in which SPNs may be
encountered: as incidental findings, during lung
cancer screening, and during evaluation of respira-
tory symptoms specific to a SPN. Next, we report the
radiographic characteristics and clinical risk factors
that assist in determining the probability of cancer.
Finally, we will discuss in detail how to integrate
probabilities and consequences to optimally
manage SPNs.
incidence of more than 40% reported in most large
studies [2]. The differential diagnosis of a SPN
includes malignant processes, such as primary lung
cancer, metastatic disease, or lymphoma, as well as
benign processes such as infection, granulomatous
inflammation, or hamartoma. Additionally, radio-
graphic opacities greater than 3 cm in diameter are
called lung masses. Greater than 90% of lung masses
are malignant [3]. Hence, masses are presumed to be
malignant until proven otherwise [4]. Multiple pul-
monary nodules have a higher probability of

Department of Pulmonary Medicine, Division of Internal Medicine, The

DEFINITION AND INCIDENCE
A SPN is defined as a single, well-marginated,
rounded radiographic opacity less than or equal to
3 cm in diameter [1]. A SPN is completely sur-
rounded by aerated lung parenchyma and is not
associated with atelectasis, hilar or mediastinal
adenopathy, or pleural effusion. The incidence of
University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Correspondence to David E. Ost, MD, MPH, Department of Pulmonary
Medicine, Division of Internal Medicine, The University of Texas MD
Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030,
USA; Tel: +1 713 563 4256; fax: +1 713 794 4922;
e-mail: dost@mdanderson.org
Curr Opin Pulm Med 2019, 25:344–353
DOI:10.1097/MCP.0000000000000586

www.co-pulmonarymedicine.com Volume 25  Number 4  July 2019

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 Management of the solitary pulmonary nodule Nasim and Ost
KEY POINTS
 Management of SPNs requires consideration of pretest
probability, diagnostic test performance, and treatment
benefits and harms beginning with the first encounter.
 The revised Fleischner Society guidelines published in
2017 have reduced the frequency of follow-up
recommendations for management of incidentally
detected pulmonary nodules with longer intervals
between subsequent CT scans recommended.
 New molecular tests may be of use when pretest
probability of cancer is low but these tests require
further study.
malignancy and are excluded from the definition of
SPN [2]. The guidelines of management for SPN do
not apply to pulmonary masses and multiple
pulmonary nodules.
CLINICAL CONTEXT AND PRESENTATION
SPN can be categorized into three different groups
based on how they present clinically: incidental
SPNs, symptom-associated SPNs, and screen-detected
SPNs. This approach to classification has utility
because the probability of the nodule being malig-
nant varies based on the clinical presentation. The
probability of lung cancer being present in turn
impacts which management algorithms will be most
effective. Clinical context also impacts the frequency
of surveillance imaging, which is discussed later.
A SPN can be seen on imaging performed for
nonpulmonary clinical indications and this is
termed an incidental SPN. An example would be a
patient complaining of abdominal pain that under-
goes a CT scan of the abdomen that includes some
lower chest imaging that reveals a SPN.
A SPN may be found on chest imaging per-
formed specifically to evaluate the cause of respira-
tory symptoms. For example, a patient presenting
with cough and hemoptysis undergoes chest CT and
is found to have a SPN. These are categorized as
symptom-specific SPNs.
Finally, a SPN can be identified on a screening
low-dose computed tomography (LDCT). These are
called screen-detected SPNs. If they are identified on
the first screening test, these are called prevalence
nodules, because the probabilities are reflective of
the prevalence of nodules and disease in the popu-
lation at one point in time. If a SPN is identified on a
subsequent screening LDCT after the first LDCT,
then it is called an incidence nodule, because the
probabilities reflect the incidence of developing new
nodules and cancer during the interval between
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screening CT’s. When using the current recommen-
dations for screening for lung cancer in high-risk
populations, the frequency of finding an abnormal-
ity on a screening LDCT ranges from 40–60% in
&&
various studies [5 ]. Many of the abnormalities
detected on these scans are often not suspicious
for cancer. In the national lung cancer screening
trial, lung abnormalities were identified on initial
screening CT in 27.3% of patients, many of these
(10.2%) were deemed radiologically to be nonsuspi-
cious for lung cancer. The remaining 17.1% of
abnormalities were deemed suspicious for lung can-
cer. The probability of lung cancer in these nodules
that were deemed suspicious for cancer during the
first LDCT (i.e., prevalence screen) was 6%. During
subsequent incidence screens, 27.9% of patients had
new lung abnormalities. Many of these (6.1%) were
deemed radiologically to be nonsuspicious for lung
cancer. The remaining 21.8% of abnormalities were
deemed suspicious for lung cancer. The probability
of malignancy in these incidence nodules that were
deemed suspicious for cancer during their incidence
screens ranged from 3% to 8% [6].
RADIOGRAPHIC RISK STRATIFICATION OF
MALIGNANCY IN SOLITARY PULMONARY
NODULE
Accurate CT characterization of SPNs is important to
differentiate between benign and malignant pro-
cesses. Variables that can help risk stratify a nodule
in terms of risk of malignancy that are available on CT
imaging include nodule size, shape, borders, density,
presence of calcification, calcification pattern, rate of
growth, and lobar location. The probability of malig-
nancy increases with larger SPN size and nodule size is
a dominant factor in management considerations of
a SPN. The risk of cancer in nodules detected during
lung cancer screening that are smaller than 6 mm is
estimated at less than 1%. An estimated average risk
of 0.5–2.0% is reported in SPNs measuring 6–8 mm.
The risk is over 3% in nodules measuring greater than
8 mm. These estimates are derived from screening
studies identifying prevalent nodules most notably
the PanCan, BCCA, and NELSON trials [7 ].
&&
For SPN that measure 11–20 mm in diameter,
the prevalence of malignancy is 33–60%, and 64–
82% in SPNs that measure greater than 20 mm in
diameter [8].
SPN border characteristics also provide insight
into the probability of malignancy. SPNs with
smooth borders have the lowest probability of
malignancy and are likely to be benign. In order
from lowest risk to highest risk, border character-
istics associated with malignancy are irregular less
than lobulated less than spiculated (Fig. 1).
www.co-pulmonarymedicine.com 345
Neoplasms of the lung with imaging
FIGURE 1. Border characteristics of solitary pulmonary nodules.
Beyond an appreciation for shape and borders of a
SPN, the density of a nodule can also provide infor-
mation as to the risk of malignancy in a SPN. Nodule
density can be classified as solid, subsolid (also called
part ground glass or semisolid), and ground glass.
Nodules with a pure ground glass or subsolid appear-
ance have a higher probability of malignancy than
pure solid nodules [3]. Subsolid nodules have the
highest frequency of malignancy of 63% and pure
ground glass opacities have a frequency of malignancy
of 18%. Incidence of malignancy in solid nodules is
estimated to be 7% [9]. If the solid component of a
subsolid SPN increases over time, this is strongly asso-
ciated with malignancy [10].
Calcifications patterns if present in a SPN can
also be informative as to whether the nodule is
malignant or not. Calcification patterns that are
associated with a high likelihood of being benign
are: laminated, popcorn, diffuse, or central calcifi-
cation. Stippled and eccentric calcification patterns
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are associated with a higher probability of malig-
nancy [11].
The rate of growth of a SPN is measured in volume
doubling times and if old images are available this can
be very informative as to the probability of malig-
nancy in a SPN [12]. The volume doubling time of a
SPN is defined as the number of days in which a
nodule doubles in volume. SPNs increasing in size
over a short period of time have lower volume dou-
bling times. Most malignant SPNs have volume dou-
bling times between 30 and 400 days [13]. Prior
imaging with a chest CT is needed for comparison
to ascertain the volume doubling time.
Finally, a SPN located in the upper lobe has a risk
of lung cancer of 1–5% higher than a lower lobe
location. Large studies of screening-detected and
incidentally detected peripheral adenocarcinomas
have shown a higher frequency of malignancy
among upper lobe lesions and in right-sided lesions
[14].
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 Management of the solitary pulmonary nodule Nasim and Ost

MANAGEMENT OF SOLITARY with serial CT imaging. If the lesion remains

PULMONARY NODULE
Management options for SPNs include watchful
waiting with follow-up CT imaging, PET imaging,
or further invasive testing. Invasive testing is used to
obtain a tissue biopsy to try to establish a diagnosis.
We will describe recent developments in these
approaches in the sections below.
Decision-making in solitary pulmonary nodule
Clinicians should estimate the pretest probability of
malignancy in a patient with a SPN by evaluating
clinical risk factors and radiographic features. Pre-
diction models have been developed using logistic
regression and validated to estimate pretest proba-
unchanged, additional careful observation with serial
CT is warranted. The frequency of CT imaging
depends on whether the SPN is a screen-detected
nodule or an incidentally identified SPN. Table 1 sum-
marizes the current recommendations based on soci-
ety guidelines. If the nodule was identified during lung
cancer screening, then the Lung Imaging Reporting
and Data System 2014 guidelines and National Com-
prehensive Cancer Network (NCCN) guidelines apply
[20]. The NCCN guidelines were updated in 2018. In
2018, the NCCN cutoff thresholds for lung nodules
were revised to reflect the Lung Imaging Reporting and
Data System cutoffs. Conversely, if the nodule was
identified incidentally, then the Fleischner Society
guidelines are more applicable [7 ]. The revised
&&

bility of lung cancer. These are available with free
web-based applications [15–17]. These prediction
models use three clinical characteristics that were
identified as independent predictors of malignancy.
These three characteristics are age, smoking history,
and history of a prior cancer diagnosis. For a typical
patient who is a surgical candidate in which the SPN
is peripheral and is amenable to a wedge resection, a
low pretest probability is less than 5%, 5–65% is
considered intermediate, and more than 65% is
considered high pretest probability [18,19]. Optimal
management strategy varies based on the patient’s
pretest probability of cancer and their functional
status and comorbidities.
Solitary pulmonary nodule with low
probability of malignancy
Patients with a SPN and a low probability of malig-
nancy are managed with periods of careful observation
Fleischner Society guidelines were published in 2017.
The revised Fleischner Society guidelines
reduced the frequency of follow-up for management
of incidentally detected pulmonary nodules as com-
pared to prior guidelines. The recommendations are
based on an estimated risk of cancer in solid SPNs
6 mm or less to be less than 1% even in heavy
smokers, and the risk in nonsmokers to be less than
0.15%. The 2017 Fleischner guidelines replace the
recommendations for solid nodules published in
2005 [21] and subsolid pulmonary nodules pub-
lished in 2013 [22]. Overall, there are longer inter-
vals recommended between scans for even high-risk
individuals with nodules more than 6 mm. Solid
SPN 6 mm or less in diameter in low-risk adults more
than 35 years old need no further follow-up. In high-
risk individuals, a follow-up CT scan is optional. The
recommendations apply even if multiple solid pul-
monary nodules 6 mm or less are present. The prior

Table 1. Available society guidelines for pulmonary nodule management

Recommended follow-up
Solitary pulmonary nodule Incidental SPN Screen-detected SPN
&& &&
Nodule type Size, mm Fleischner 2017[7 ] NCCN 2018[45 ] Lung-RADS 2014 [20]

Solid <6 None for low risk, 12 mth Annual screening Annual screening
optional for high risk
6–8 One scan at 6–12 mth, One scan at 6 mth One scan at 6 mth,
18–24 mth annual screening
>8 One scan at 3 mth, PET, One scan at 3 mth, PET, tissue One scan at 3 mth,
or tissue sampling sampling for high risk annual screening
Part solid <6 None Annual screening Annual screening
6 One scan at 3–6 mth, Based on size of Based on size of solid
every 12 mth  5 yrs solid component component
Ground glass <6 None Annual screening Annual screening
6 One scan at 6–12 mth, Annual screening Annual screening up to
every 24 mth until 5 yrs 20 mm

Lung-RADS, Lung Imaging Reporting and Data System; mth, months; NCCN, National Comprehensive Cancer Network; SPN, solitary pulmonary nodule; yrs,
years.

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Neoplasms of the lung with imaging
Fleischner Society guidelines had advised no follow-
up in solid nodules 4 mm or less in low-risk patients,
and a single follow-up CT scan in 12 months
in high-risk patients with solid nodule(s) 4 mm
or less.
If the SPN is stable for 2 years then it can be
considered benign. A notable exception to this is
that ground glass opacifications, which may repre-
sent more indolent carcinoma in situ, may require a
longer period of observation as growth may be
slower. Current recommendations suggest that
ground glass opacifications be observed for up to
&&
4 years [7 ]. If a SPN demonstrates growth on
follow-up imaging then a biopsy procedure is
usually warranted. The benefit of this strategy is
the avoidance of invasive diagnostic procedures
and unnecessary surgery in individuals with benign
disease [23]. The risk of this strategy is that it can
delay diagnosis of malignancy.
Solitary pulmonary nodule with an
intermediate probability of malignancy
Patients with an intermediate probability of cancer
will typically undergo additional diagnostic testing
to further revise the probability of malignancy until
either observation or treatment becomes more
clearly indicated [2]. Depending on the diagnostic
test result, the probability of disease will either
increase or decrease. This posterior probability of
disease, defined as the probability of disease given
the test results, can be calculated using Bayes’ theo-
rem provided we know the pretest probability of
disease and the test characteristics (i.e., sensitivity
and specificity or alternatively the likelihood ratio
for the given test result) [18]. For patients with an
intermediate probability of disease, diagnostic test
options include PET, tissue biopsy techniques such
as CT-guided percutaneous biopsy and broncho-
scopic biopsy, and more recently some more
advanced molecular tests.
PET imaging in solitary pulmonary nodule
PET is used as a modality to investigate solid nodules
of at least 8 mm in the American College of Chest
Physician guidelines [24]. PET imaging of SPNs is
useful for assessment of occult metastasis to the
mediastinal lymph nodes and for detection of occult
distant metastasis (except for brain metastases). The
sensitivity and specificity of PET for identifying
malignancy in the nodule itself are both approxi-
mately 85% [25]. Accordingly, PET has a high nega-
tive predictive value when the pretest probability of
cancer is low, and such patients can be subsequently
managed with careful observation. PET does have
an important limitation. PET is less sensitive for
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nodules less than 8–10 mm in diameter so PET is
not useful for studying smaller nodules [26,27].
Tissue biopsy techniques for solitary
pulmonary nodules
A diagnostic biopsy is necessary to establish the
cause of a SPN in high-risk patients or those with
nodules of at least 8 mm. If the SPN is malignant,
adequate tissue is needed to subtype the cancer and
assess for molecular markers. The main techniques
for obtaining tissue are CT-guided percutaneous
biopsy and bronchoscopy. The optimal choice of
procedure is based on the location and size of the
SPN, CT characteristics, as well as an assessment of
the risks and benefits of each potential treatment
strategy. Table 2 summarizes available diagnostic
modalities and their diagnostic sensitivity and com-
plication rates. Bronchoscopic sensitivity increases
with lesion size and is higher for centrally located
lesions. A positive bronchus sign, defined as a CT
image where a bronchus can be seen leading directly
to a pulmonary nodule (Fig. 2) is also associated with
higher bronchoscopic sensitivity [28,29].
A meta-analysis of flexible bronchoscopy for
peripheral lesions with radial probe endobronchial
ultrasound (EBUS) reported sensitivity for lung cancer
ranging from 49–88% with significant statistical and
clinical heterogeneity between studies [30]. More
recent data such as American College of Chest Physi-
cians Quality Improvement Registry, Evaluation, and
Education registry reports a sensitivity ranging from
56% to 70% for flexible bronchoscopy for peripheral
lesions with radial probe EBUS [31 ].
&
Meta-analysis of electromagnetic navigation
(EMN) bronchoscopy has a sensitivity of 71.1–
82% for peripheral lung nodules [32,33]. Registry
data from American College of Chest Physicians
Quality Improvement Registry, Evaluation, and
Education has reported a lower sensitivity of 54–
&
69% [31 ]. This is comparable to a recent prospective
Table 2. Diagnostic modalities for tissue diagnosis of
solitary pulmonary nodule and their yield
Diagnostic modality Sensitivity Complications
Peripheral bronchoscopy 56–70% Pneumothorax 1.7%
with radial probe [31 ]
&
Bleeding 0.2%
Respiratory failure 0.2%
EMN bronchoscopy [34 ] 69% Pneumothorax 2.9%
&
Bleeding 1.5%
Respiratory failure 0.7%
CT-guided transthoracic 90% Pneumothorax 15%
needle aspiration [14] Bleeding 1%,
Respiratory failure 0.6%
EMN, electromagnetic navigation.
Volume 25  Number 4  July 2019
 Management of the solitary pulmonary nodule Nasim and Ost
FIGURE 2. A solitary pulmonary nodule with a positive
bronchus sign.
trial of EMN bronchoscopy for pulmonary nodules
with a median size of 20 mm with a reported sensi-
&
tivity of 69% [34 ].
Although CT-guided percutaneous transtho-
racic needle aspiration has the highest sensitivity
of 90%, the incidence of pneumothorax following
CT-guided biopsy is also significantly higher rang-
ing from 15% to 38% [35,36]. The risk of pneumo-
thorax is higher with lesion size of less than 10 mm,
lesion depth of more than 20 mm from the pleural
surface, and the presence of pulmonary fissure in the
way of the needle tract [37,38].
Molecular techniques
An integrated classifier using multiple reaction
monitoring mass spectrometry to measure the rela-
tive abundance of two plasma proteins (LG3BP and
C163A) has been developed and was trained on an
independent sample of 222 prospectively collected
plasma samples from patients with nodules measur-
ing 8–20 mm in size [39]. The test was refined spe-
cifically to improve performance for nodules with
lower risk of malignancy. The goal was to effectively
‘rule out’ lung cancer in nodules that have a low risk
of cancer to begin with. This classifier was then
applied in a second prospective multicenter obser-
vational clinical validation study to determine the
performance characteristics of the integrated classi-
&
fier [40 ]. The integrated classifier demonstrated a
sensitivity of 97% and a specificity of 44%. In the
intended use cohort, the investigators tabulated
what the classifier would have recommended and
the number of invasive tests that could have been
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saved as well as the number of malignant nodules
that were misclassified as benign. They estimated
that 40% fewer procedures would be performed if
the classifier was used, whereas 3% of malignant
nodules would be misclassified as benign. Because of
the potential for malignant nodule misclassifica-
tion, it is important to recognize that the classifier
does not definitively rule out cancer. Clinically this
means that if the patient’s pretest probability of
cancer is low and the classifier suggests a benign
diagnosis, the patient should still undergo serial CT
follow-up to ensure radiographic stability for 2
years. In this way, misclassified nodules will be
subsequently identified based on growth and
brought to biopsy. Additional studies are needed
to determine the actual clinical utility of the test
in terms of the number of invasive biopsies saved
versus the number of cancers that have a delay in
their diagnosis because of misclassification.
Solitary pulmonary nodule with high
probability of malignancy
Patients with a high probability of cancer (>65%) can
be managed with diagnostic and potentially curative
surgical resection [41,42]. If the lesion is peripheral, a
wedge biopsy is done first, and intraoperative frozen
section determines whether the nodule is malignant.
If the frozen section shows a benign cause, no addi-
tional resection is required. Operative mortality with
a wedge resection is around 0.5%. When a SPN is
found to be malignant on wedge resection, the resec-
tion can then be converted to a completion lobec-
tomy intraoperatively. Mortality associated with a
lobectomy is 1–4% [8]. The advantage of this surgical
approach is the dual benefit of definitive treatment at
the time of diagnosis if the SPN is malignant while
limiting harm if the lesion is found to be benign
(assuming a wedge resection is feasible) [18]. It is
important to recognize that wedge resection is not
always feasible, which is especially true for centrally
located lesions.
In patients with multiple comorbid conditions
and a high clinical suspicion of lung cancer without
pathological confirmation of SPN, stereotactic body
radiation therapy remains an option [43,44]. How-
ever in most instances, a tissue biopsy should be
obtained prior to initiation of stereotactic body
radiation therapy.
Integrating comorbidities to adjust decision
thresholds
As shown in the above discussion, management
strategies vary depending on whether a patient
has low, intermediate, or high probability of cancer.
www.co-pulmonarymedicine.com 349
Neoplasms of the lung with imaging
The probability thresholds that separate low from
intermediate and intermediate from high are
referred to as decision thresholds because they deter-
mine strategy. (Fig. 3) However, it is critical to
recognize that decision thresholds vary between
patients considerably. These decision thresholds
are a function of the potential for benefit and harm
of treatment and the test characteristics of the avail-
able diagnostic tests.
Benefit in this context is defined as the differ-
ence in outcomes between identical patients that
have disease, one of whom receives treatment and
the other who receives no treatment. Harm is
defined as the difference in outcomes between iden-
tical patients that do not have disease, one of whom
receives no treatment and the other who receives
treatment. Note that benefit is predicated on
patients having disease, whereas harm is predicated
on patients having no disease. Also note that harm is
predicated on at least some of the treatments result-
ing in complications or side-effects that have an
adverse impact. Also note that benefit and harm
are not probabilities rather they are consequences
of actions taken in a given context.
The treatment threshold is defined as the prob-
ability of disease at which treatment and no treat-
ment would result in similar outcomes. If the
probability of disease is above the treatment thresh-
old, then treatment will be a better strategy. If the
probability of disease is less than the treatment
FIGURE 3. Decision thresholds are the pretest probabilities of malignancy. Source: image adapted with permission.
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threshold, not treating will be better. The treatment
threshold is a function of the potential for harm and
benefit of the treatment, as described in the formula:
Treatment threshold ¼ harm=ðharm þ benefitÞ ¼ 1=½1 þ ðbenefit=harmÞ:
When the potential for harm is high relative to
benefit, this probability approaches 1 meaning that
treatment requires a very high probability of disease.
Conversely, if harms are almost zero and benefits are
large, then even a very low probability of disease
might warrant treatment.
For a given patient, if the result of a diagnostic
test could potentially shift the pretest probability of
disease from one side of the treatment threshold to
the other (e.g., from low to high), then that test is
potentially useful. If the pretest probability of dis-
ease is so low or so high, or if the test is not very
effective, then it may be that whether the test result
is positive or negative, the resulting posterior prob-
ability will be on the same side of the treatment
threshold. In such a case, the test will not be useful,
as it will result in no actionable information.
Decision thresholds are the pretest probabilities
of disease at which testing goes from being not
useful and unactionable to being useful and action-
able (lower decision threshold, 5% in the above
discussion) and from being useful and actionable
to being not useful and unactionable (higher deci-
sion threshold, 65% in the above discussion). They
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 Management of the solitary pulmonary nodule Nasim and Ost

are a function of the test’s sensitivity and specificity
as well as the treatment threshold. The more sensi-
tive and specific a test is, the broader the range of
pretest probabilities over which the test will
be useful.
Based on the above conceptual framework, it is
clear that the potential for benefit and harm as well
as test characteristics plays a pivotal role in deter-
mining the decision threshold. The treatment
threshold will vary if the potential for benefit and
harm is different between individuals. So if a patient
with a SPN is 88 years old, has chronic obstructive
pulmonary disease, is just barely a surgical candidate
for lobectomy, and has a central lesion that makes a
wedge resection impossible, the potential for harm
from surgery is very high (remembering that harm is
predicated on the patient not having cancer). The
reason is that surgery will entail a lobectomy rather
than a wedge resection, so the potential for harm
will be higher. In addition, the patient’s chronic
obstructive pulmonary disease means the complica-
tion rate will be higher than the mean of the popu-
lation. If the potential for harm is higher and
benefits are unchanged, then the treatment thresh-
old must be higher – in other words, we require
more evidence to ‘pull the trigger’ on treatment. If
the treatment threshold moves higher, then the
decision thresholds will also move higher.
Similarly, the potential for benefit may vary
between patients depending on their comorbidities.
If a patient has a SPN but already has a different cancer
(e.g., glioblastoma), then the competing risk of death
from glioblastoma lowers the magnitude of the poten-
tial for benefit from resection of a malignant SPN. The
benefit will go down disproportionately more than the
harm, so the treatment threshold will move higher.
The American College of Chest Physician guide-
line algorithms and indeed all guideline algorithms
on SPNs use thresholds based on certain assump-
tions, although these assumptions are not always

FIGURE 4. American College of Chest Physician algorithm for solid solitary pulmonary nodule assessment based on decision
thresholds. The assumptions underlying this algorithm include peripheral location of the solitary pulmonary nodule, patient
preferences for surgical resection (if necessary) and age, comorbidities, and forced expiratory volume in one second
acceptable for surgical candidacy. Source: Image adapted with permission.

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Neoplasms of the lung with imaging
explicitly stated in the algorithm. (Fig. 4) This can
lead to mistakes in application in clinical practice, as
the thresholds only are valid when the underlying
assumptions are true. So the abovementioned 5%
and 65% decision thresholds apply to patients who
are good surgical candidates with relatively a few
other comorbidities that have a peripheral lesion
that is amenable to wedge resection. This is the
‘average’ case, but each patient is different and there
is wide variability between patients, so it will be rare
that any given patient actually perfectly fits this
ideal scenario. Rigid conformity to one recom-
mended pair of decision thresholds will yield poor
results. Rather, the proper use of these algorithms is
to provide a conceptual framework to approach the
patient. The probabilities provided help to calibrate
readers to what might be considered as a common
case. Proper use of the guidelines requires recogni-
tion of the magnitude of variability in the popula-
tion, as physicians treat individual patients, not
populations. Because of the wide variability between
patients, each individual patient’s treatment thresh-
old and decision thresholds need to be estimated.
This highlights a deeper underlying concept,
namely, that optimal diagnostic strategy must take
into consideration all possible treatment strategies.
Medical problems are often conceptualized as first
make a diagnosis and once that is established think
about treatment. This approach will lead to mistakes,
because the best diagnostic strategy will depend on
what the treatment options are. So optimal decision
strategies must take into account not only probabili-
ties but also consequences (e.g., benefit and harm).
CONCLUSION
SPNs management requires assessment of pretest
probability, understanding of the test characteristics
of various diagnostic options, and consideration of
consequences (i.e., benefits and harms). Clinical
presentation (symptomatic, incidental, and screen
detected), clinical risk factors (e.g., smoking his-
tory), and radiographic features inform pretest prob-
ability. PET imaging, CT-guided biopsy, and
bronchoscopic biopsy techniques represent the
main diagnostic options. Newer molecular diagnos-
tic risk stratification methods may also be useful in
select circumstances although these require further
study. Integration of the potential for benefits and
harms along with knowledge of diagnostic test per-
formance facilitates determination of appropriate
decision thresholds for individual patients. These
thresholds vary significantly between patients.
When pretest probability is lower than the first
decision threshold (e.g., 5% in some individuals) a
careful observation strategy with serial CT imaging
352 www.co-pulmonarymedicine.com
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
is warranted. The recommended frequency of serial
CT imaging for incidentally detected nodules in this
low probability category has changed recently, with
longer intervals being recommended in the 2017
Fleischner Society guidelines published. When pre-
test probability is in the intermediate range between
decision thresholds (e.g., 5–65% in some individu-
als), diagnostic testing is warranted. Newer molecu-
lar techniques may be of use in certain select
situations when the pretest probability is toward
the lower end of this intermediate range. Successful
management of the SPN requires integration of all of
these different considerations at the beginning
when the SPN is first identified, rather than waiting
to consider treatment options until after a diagnosis
is made.
Acknowledgements
None.
Financial support and sponsorship
None.
Conflicts of interest
There are no conflicts of interest.
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