The Pittsburgh Lung Screening Study (PLuSS): Outcomes
within 3 years of a first CT scan
David O. Wilson MD, MPH (1), Joel L. Weissfeld MD, MPH (2), Carl R. Fuhrman MD (3),
Stephen N. Fisher MD (3), Paula Balogh CRNP (2), Rodney J. Landreneau MD (4), James D.
Luketich MD (4), and Jill M. Siegfried PhD (5)
1. Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine
2. Department of Epidemiology
3. Department of Radiology
4. Heart, Lung, Esophageal Surgery Institute, Department of Surgery
5. Department of Pharmacology, University of Pittsburgh, Pittsburgh, PA
Supported by the University of Pittsburgh Lung Cancer SPORE: NCI P50-CA90440,
University of Pittsburgh Cancer Institute and University of Pittsburgh Medical Center
Word count: 3,967
David O. Wilson, M.D., M.P.H
580 S. Aiken Ave., Suite 400
Pittsburgh, PA 15232
AJRCCM Articles in Press. Published on July 17, 2008 as doi:10.1164/rccm.200802-336OC
Copyright (C) 2008 by the American Thoracic Society.
This manuscript has an Online Data Supplement which is accessible in this issue's table of content online at www.
Objective: To report findings from initial and one-year repeat screening low-radiation-dose
computed tomography (CT) of the chest and three-year outcomes for 50 to 79 year-old current
and ex-smokers in the Pittsburgh Lung Screening Study (PLuSS).
Methods: Notified of findings on screening CT, subjects received diagnostic advice from both
study and personal physicians. Tracking subjects for up to three years since initial screening, we
obtained medical records to document diagnostic procedures, lung cancer diagnoses, and deaths.
Results: 3,642 and 3,423 subjects had initial and repeat screening. 1,477 (40.6% of 3,624) were
told about non-calcified lung nodules on the initial screening and, before repeat screening, 821
(55.6% of 1,477, 22.5% of 3,642) obtained one or more subsequent diagnostic imaging studies
(CT, positron emission tomography - PET, or PET-CT). Tracking identified 80 subjects with
lung cancer, including 53 subjects with tumor seen at initial screening. In all, 36 subjects (1.0%
of the 3,642 screened), referred for abnormalities on either the initial or repeat screening, had a
major thoracic surgical procedure (thoracotomy, video-assisted thoracoscopic surgery - VATS,
median sternotomy, or mediastinoscopy) leading to a non-cancer final diagnosis. Out of 82
subjects with thoracotomy or VATS to exclude malignancy in a lung nodule, 28 (34.1%)
received a non-cancer final diagnosis. Forty of 69 (58%) subjects with non-small cell lung cancer
had stage I disease at diagnosis.
Conclusions: Though leading to the discovery of early stage lung cancer, CT screening also led
to many diagnostic follow-up procedures, including major thoracic surgical procedures with non-
For 2008 in the United States (U.S.), the American Cancer Society predicted 215,020 new lung
cancer diagnoses and 161,840 lung cancer deaths.1For 1996-2003, only 16% of new lung cancer
cases were localized stage at diagnosis and amenable to surgical cure.1
In the U.S., lung cancer death is more common than breast, prostate, and colorectal cancer death
combined.1Improvements in 5-year relative survival have been small for lung cancer (13% and
16% for cases diagnosed in 1975-1977 and 1996-2003, respectively), particularly when
compared to the substantial improvements seen for breast, prostate, and colorectal cancer.1
Screening for early detection is currently recommended for breast, prostate, and colorectal, but
not lung cancer.2New technologies, primarily low-radiation-dose imaging with multi-detector
helical computed tomography (CT), has revived interest in lung cancer screening. CT clearly
detects smaller lung tumors at earlier stages than conventional chest X-ray.3-8 Because of lead-
time bias, length-time bias, and over-diagnosis,9conclusions regarding the effects of screening
on lung cancer mortality must await results from randomized controlled trials ongoing in the
U.S.10 and Europe11-13. Two recent analyses of single-arm cohort studies14, 15point to the
uncertainty and associated controversy created by the absence of results from randomized control
trials. In one analysis, an international collaboration, 85% of CT-detected lung tumors were
clinical stage I.15 Moreover, persons with clinical stage I CT-detected lung cancer had favorable
10-year survival.15From these observations, the investigators concluded that annual CT
screening can detect curable lung cancer in a manner capable of preventing 80% of lung cancer
deaths.15 In contrast, comparing outcomes observed in three large studies of CT screening to
predictions from two validated risk models, the second analysis concluded that CT screening
increases lung cancer diagnosis and lung cancer resection without decreasing advanced lung
cancer or lung cancer death.14In addition to over-diagnosis (screen-detection and treatment of
clinically insignificant or indolent lung cancer), CT screening frequently detects benign
abnormalities (generally, non-malignant non-calcified lung nodules) that can lead to anxiety,
costs, and unnecessary procedures.16, 17
With a focus on major thoracic surgical procedures with non-cancer outcomes, we report
findings from initial and one-year repeat screening computed tomography (CT) of the chest and
three-year outcomes for 50 to 79 year-old current and ex-smokers in the Pittsburgh Lung
Screening Study (PLuSS), the largest single-institution CT lung cancer screening study reporting
Between January 2002 and April 2005, the Pittsburgh Lung Screening Study (PLuSS) used
advertisements and mass mailings to recruit volunteers with the following characteristics: 1) age
50-79 years, 2) no personal lung cancer history, 3) non-participation in concurrent lung cancer
screening studies, 4) no chest computed tomography (CT) within 12 months, 5) current or ex-
cigarette smoker of at least one-half pack per day for at least 25 years, and, if quit, quit for no
more that ten years before study enrollment, and 6) body weight less that 400 pounds.
Individuals were not excluded because of symptoms.
Baseline activities included completing a risk factor questionnaire, collecting peripheral blood
samples, forced expiratory spirometry conducted and analyzed in accordance with American
Thoracic Society standards18, 19, low-radiation-dose CT screening, and physician referral for non-
calcified lung nodules. Follow-up activities included repeat CT screening after 12 months and
active surveillance for lung cancer-related endpoints. Occurring between March 2002 and
September 2005 and between March 2003 and November 2006, respectively, subjects received
the initial and one-year repeat CT at study expense.
Of 9,386 persons assessed by telephone for study eligibility, we excluded 4,352 (46.4%) for
reasons related to age (N=84), lung cancer history (N=60), participation in other lung cancer
screening studies (N=1,043), recent chest CT (N=120), cigarette smoking history (duration or
dose; N=1,439), duration quit (N=1,600), and body weight (N=6) (exclusions applied in
sequential fashion). Of 5,034 eligible persons, 1,279 (25.4%) did not accept an enrollment visit
and 113 (2.2%) enrolled, but did not return for CT screening. The remaining 3,642 persons, the
study population, completed the initial CT screening a median 53 days (range 2-604 days) after
the initial telephone contact. Among eligible persons (N=5,034), CT screening occurred more
frequently in men than women (74.6 vs. 70.2%), more frequently in ex-cigarette smokers than
current cigarette smokers (76.7 vs. 69.7%), and more frequently in younger than older persons
(72.5, 73.9, and 66.5% in 50-59, 60-69, and 70-79 year-old persons, respectively). Otherwise,
CT-screened and unscreened eligible persons were similar with respect to age started smoking,
duration of cigarette smoking, and duration quit (among ex-smokers).
Screening CT imaging protocol
The lung cancer screening protocol used a single-breath-hold, helical, low-dose technique (40-60
mA, 140 kVp) to obtain axial images reconstructed with a high spatial frequency (lung)
algorithm at contiguous 2.5 mm intervals. One of two study radiologists (CRF and SNF) used
standard lung windows (1496/-555) to view images (2.5 mm section thickness) on a PACS
monitor display system (Stentor®). Radiologists adjusted window width and level, as
appropriate, to detect calcification in nodules and to evaluate mediastinal structures.
Protocol for primary interpretation of the initial screening CT
A single study radiologist identified and characterized lung nodules according to size, presence
and type of calcification (complete, central target, speckled, or peripheral), attenuation (solid,
non-solid, or mixed), border characteristic (smooth, spiculated, or lobulated), and lobar location.
The radiologist used the axial image showing the nodule to its fullest extent to measure
maximum nodule diameter and nodule diameter perpendicular to this maximum. Analyses
averaged these two diameter measurements to obtain a summary measure of nodule size, the
average diameter. The category of calcified nodule included all completely calcified nodules and
nodules (≤2.0 cm average diameter) with central target or lamellate calcification. Procedures
further divided non-calcified nodules into low (<0.5 cm average diameter or 0.5-0.9 cm average
diameter with non-spiculated border) and moderate or high lung cancer suspicion categories
(0.5-0.9 cm average diameter with spiculated border or ≥1.0 cm average diameter). Finally, the
interpreting radiologist used subjective criteria to classify larger non-calcified nodules (≥1.0 cm
average diameter) into moderate and high lung cancer suspicion categories. The initial CT study
received a preliminary summary nodule interpretation (low, moderate, or high lung cancer
suspicion) based on the rating of the most suspicious nodule. The radiologist used a locally
developed computer database application (programmed in Microsoft® Office Access 2003) to
enter visual CT findings. The application used pre-programmed algorithms to map the visual
findings into lung nodule ratings and summary interpretations, as defined above and summarized
in Appendix Table 1. Intended to encompass less than 5%, 5-50%, and greater than 50% pre-
biopsy lung cancer probabilities, respectively, we conceived the low, moderate, and high lung
cancer suspicion categories in order to guide referral recommendations and subsequent
Protocol for primary interpretation of the repeat screening CT
The primary interpretation of the repeat screening CT also included a direct visual comparison of
initial and repeat CT images. Specifically, a single study radiologist relocated each non-calcified
lung nodule noted at baseline and applied subjective criteria to interpret temporal change
according to a forced-choice format (suspicious change vs. no significant change vs. partial
resolution vs. complete resolution), with suspicious change defined as increase in size or density
of a pre-existing nodule. The radiologist also identified and characterized non-calcified lung
nodules, visible on repeat CT images, but not enumerated at baseline. The radiologist used the
same forced-choice format to report temporal change in nodules, first identified on the repeat CT
images, but visible, in retrospect, on the initial CT images.
A computer algorithm, programmed into our Access database application, assigned the moderate
lung cancer suspicion rating to every non-calcified lung nodule that either first appeared on
repeat CT or showed suspicious change from baseline. The radiologist was allowed to use
subjective criteria to assign a high lung cancer suspicion rating to nodules in this category. The
algorithm assigned the low lung cancer suspicion rating to nodules showing no significant
change between initial and repeat CT. The repeat screening received a preliminary summary
nodule interpretation (low, moderate, or high lung cancer suspicion) based on the rating of the
most suspicious nodule.
Secondary review procedures
By protocol, a committee, that included study radiologists, pulmonologists, and other
investigators, met in conference and reviewed all CT studies with preliminary moderate or high
suspicion nodule interpretations and some low suspicion CT studies with larger (≥0.5 cm)
nodules. Using subjective clinical criteria and the totality of findings present on all available CT
studies, the committee reached consensus regarding a final summary nodule interpretation (no,
low, moderate, or high lung cancer suspicion).
For each screening CT study, the investigators prepared a written report containing detailed
radiological findings and final summary interpretations. The subject and one personal physician
received the written report, by mail, along with a cover letter and explanatory information. Based
on the final summary nodule interpretation, written materials advised physician-directed
diagnostic follow-up for persons with moderate to high lung cancer suspicion and interval
diagnostic CT follow-up for persons with low lung cancer suspicion. Subjects could also receive
a recommendation for physician-directed diagnostic follow-up for central airway abnormalities,
thoracic lymph enlargements, or other clinically significant incidental findings.
To coincide with the postal delivery of written reports, a nurse practitioner telephoned every
subject with any CT finding that generated a follow-up recommendation. The nurse practitioner
summarized relevant CT findings and referral recommendations and described follow-up
options, options that could include either a consultation visit with the study pulmonologist
(DOW) or a no-fee physician office visit with the principal investigator (JLW). Again, based on
the final summary nodule interpretation, the investigators generally advised thoracoscopy with
excisional biopsy or mediastinoscopy for persons with high suspicion, additional diagnostic
imaging studies (thoracic CT, positron emission tomography - PET, or PET-CT) after no greater
than three month delay for persons with moderate suspicion, and interval periodic thoracic CT
for persons with low suspicion, in accordance with published guidelines. During the first year of
our study, we advised repeat CT in 6 months for persons with only small (<0.4 cm) low
suspicion nodules and repeat CT in 3 to 6 months for persons with larger (≥0.4 cm) low
suspicion nodules. After the first year, we responded to evolving opinion regarding the
management of small CT screen-detected nodules4, 8, 20, 21 and began to recommend annual repeat
CT screening for persons with only micro-nodules (<0.4 cm) and 6-month CT follow-up for
persons with larger (≥0.4 cm) nodules.
Tracking/surveillance of study endpoints
To document diagnostic events and outcomes, the nurse practitioner maintained telephone
contact with persons who had received a follow-up recommendation. At annual intervals, the
investigators used brief telephone interviews and/or mailed questionnaires to update the vital and
cancer status of study subjects and to ascertain interval lung biopsy procedures. Follow-up was
99%, 98%, and 80% complete at the one, two, and three year time points, respectively. Using
information obtained over the telephone and signed consents, the investigators identified,
acquired, and reviewed relevant medical records, including images and reports from imaging
studies (thoracic CT, PET, or PET-CT), biopsy procedure reports, pathology reports, and death
Focusing on clinical indications and outcomes, one author (DOW) reviewed the assembled
medical records of 1) every subject who received a lung cancer diagnosis and 2) every subject,
with a follow-up recommendation, who subsequently experienced an invasive diagnostic
procedure. The same author and a certified tumor registrar independently staged every lung
cancer case and met in conference to reconcile disagreements. We report only lung cancer
diagnoses and invasive diagnostic procedures that occurred within two years of the repeat CT or,
for persons without repeat CT, within three years of the initial CT.
The institutional review board for the University of Pittsburgh approved the research.
Subject characteristics (Table 1)
The 3,642 subjects with initial CT screening included 1,872 men and 1,770 women, 7.1% non-
white race or Hispanic ethnicity, mean age 59 years, 42.7% 60+ years of age, median 47 pack-
year cigarette smoking history (33-62 pack-year inter-quartile range- IQR), 14% self-reporting
any prior history of chest CT, and median 1.8% (1.0-3.4% IQR) calculated 5-year incident lung
cancer risk22. Table 1 distributes subjects according to age, cigarette smoking status, pack-years,
personal history of lung disease, family cancer history, and pulmonary function.
Findings at initial CT screening
We referred 1,477 subjects (40.6% of 3,642; Table 2) because of the finding of one or more non-
calcified lung nodules at the initial CT screening. Among those screened, 856 (23.5%) had one
non-calcified nodule and 621 (17.1%) more than one. Forty (1.1%) and 182 (5.0%) were referred
because of high and moderate lung cancer suspicion, respectively (Table 2).
Compliance with repeat CT screening
Within 365 days of the initial CT screening, 36 persons (17 men and 19 women) were diagnosed
with primary lung cancer and an additional 14 persons died (11 men and three women). Of the
remaining 3,592 subjects eligible, 3,423 (95.3%) complied with repeat screening. Compliance
with repeat screening was similar among men (95.8%) and women (94.7%; p = 0.12). Median
time elapsing between initial and repeat CT screening was 385 days (371-406 IQR).
Lung nodule findings on repeat screening CT
Reevaluation at repeat CT screening of 2,497 non-calcified nodules seen at baseline showed
suspicious change in 81 (3.2%), no change in 1,930 (77.3%), partial resolution in 276 (11.1%),
complete resolution in 192 (7.7%), and calcification in 18 (0.7%). Using a hierarchy (suspicious
change, no change, partial resolution, complete resolution, and calcification) to classify persons
with more than one nodule, repeat CT screening in 1,386 subjects with one or more non-calcified
baseline nodules showed suspicious change in 75 (5.4%), no change in 1,110 (80.1%), partial
resolution in 108 (7.8%), complete resolution in 82 (5.9%), and calcification in 11 (0.8%). Of
358 non-calcified nodules first seen on repeat CT, but visible in retrospect on initial CT, 66
(18.4%) showed suspicious change, 284 (79.3%) no change, and 8 (2.2%) partial resolution. The
same hierarchical classification of 302 subjects with one or more non-calcified nodules first seen
on repeat CT, but visible in retrospect on initial CT, showed suspicious change in 64 (21.2%)
showed, no change in 232 (76.8%), and partial resolution in 6 (2.0%). Finally, 339 non-calcified
nodules were visible in 256 subjects (7.5% of 3,423) on the repeat CT, but not on the initial CT.
We referred 1,450 subjects (42.4% of 3,423) because of new or changed nodules, 18 (0.5% of
3,423) and 206 (6.0% of 3,423) with high and moderate lung cancer suspicion, respectively
(Table 2). In a subgroup of 1,928 subjects without reason for referral after initial screen, we
referred 231 (12.0%) because of new nodules, including 2 (0.1%) and 92 (4.8%) with high and
moderate lung cancer suspicion, respectively (web supplement). The web supplement contains a
detailed account of repeat CT screen results in other subgroups defined according to results on
the initial screen.
In the interval between initial and repeat CT (or within 365 days of initial CT for persons without
repeat CT), tracking procedures documented 1,070 diagnostic imaging studies (thoracic CT,
PET, or PET-CT; Table 2) in 821 (55.6% of 1,477) persons referred because of a non-calcified
lung nodule seen at initial CT. One-hundred ninety three (193; 86.9%) of 222 subjects referred
because of a high or moderate suspicion nodule received 333 diagnostic imaging studies and 628
(50.0%) of 1,255 subjects referred because of a low suspicion nodule received 737 studies
(p<.0001, 86.9 vs. 50%). Three hundred nine (309; 40.2%) of 768 subjects referred because of
small (<0.5 cm) low suspicion nodule received 357 diagnostic imaging studies and 319 (65.5%)
of 487 subjects referred for larger (≥0.5 cm) low suspicion nodule received 380 diagnostic
imaging studies (p<.0001, 40.2 vs. 65.5%).
We identified 36 subjects (1.0% of 3,642) who were referred for abnormalities on either the
initial or repeat screening and who subsequently received a non-cancer diagnosis after a major
thoracic surgical procedure. Classified according to the most invasive procedure, these 36
subjects included nine with thoracotomy, 21 with video-assisted thoracoscopic surgery (VATS),
two with median sternotomy, and four with mediastinoscopy. The two median sternotomy
procedures were performed to remove a thymic cyst and a bronchogenic cyst seen on initial CT.
The four mediastinoscopy procedures were performed to evaluate abnormal PET in the
mediastinum (1 subject) or to evaluate enlarged lymph nodes seen on initial CT (3 subjects,
including 2 diagnosed with sarcoidosis).
The group of 30 subjects with thoracotomy or VATS included 28 subjects with lung resection to
exclude malignancy in a lung nodule (Table 3), one subject with thoracotomy with
emphysematous bleb resection to treat spontaneous pneumothorax, and one subject with VATS
wedge resection to diagnose interstitial lung disease. The 28 subjects with thoracotomy or VATS
lung resection to exclude malignant lung nodule comprised 0.8% (95% confidence interval
(exact binomial; CI): 0.5 to 1.1%) of 3,642 screened subjects and 1.6% (95% CI: 1.1 to 2.3%) of
1,726 subjects with a referral recommendation for non-calcified nodule on either initial or repeat
CT. These 28 subjects received non-lung cancer diagnoses of limited or no clinical significance
(e.g., fibrosis, bronchiolitis, pneumonitis, intrapulmonary lymph node, etc.; Table 3). Notably,
these 28 subjects typically underwent thoracotomy or VATS against the primary
recommendation or without the advice of clinical investigators attached to the CT screening
program (Table 3). Out of 80 subjects with primary lung cancer diagnosed within two years of
the repeat screening or, for subjects without repeat screening, within three years of the initial
screening (Table 4), we identified 54 subjects who had thoracotomy or VATS for either the
diagnosis or treatment of lung cancer (Table 3). Therefore, in the setting of CT screening, we
observed 28 and 54 subjects who experienced thoracotomy or VATS with benign and lung
cancer outcomes, respectively, a ratio of 1 to 2.
Eighty (80) subjects (2.2% cumulative incidence, 95% CI: 1.7 to 2.7%) had primary lung cancer
diagnosed within two years of the repeat screening or, for subjects without repeat screening,
within three years of the initial screening. Table 4 distributes these subjects according to manner
of detection (primary tumor reported or not reported on the initial CT as an abnormality in need
of diagnostic follow-up), cell type (small cell or non-small cell), and diagnostic stage. Notably,
40 (58.0%, 95% CI: 45.5 to 69.8%) of 69 non-small cell lung cancer cases and 31 (59.6%, 95%
CI: 45.1% to 73.0%) of 52 non-small cell lung cancer cases with manifestations visible at initial
screening were early stage (stage I).
Tracking of subjects referred for abnormalities seen on initial or repeat CT identified nine
subjects with cancer diagnoses other than primary lung cancer (two Hodgkin’s disease, two
lymphoma, and five cancers metastatic to lung).
Low-radiation-dose helical CT hopes to reduce lung cancer mortality through early detection. In
a high risk cohort (N=3,642; mean age 59 years, median 47 pack-year cigarette smoking history,
and 43% with airflow obstruction; Table 1), we report findings from initial CT followed by
repeat CT one year later and clinical outcomes observed within three years of initial screening.
Follow-up showed lung cancer detected at early stage (Table 4), though at the cost of frequent
referral for CT-related abnormalities (Table 2).
As shown in Table 2, we delivered a follow-up recommendation to 1,477 subjects (40.6% of
3,642) with non-calcified nodules on an initial CT. The initial CT identified 40 (1.1%) subjects
with high suspicion and 182 (5.0%) subjects with moderate suspicion nodules, representing
≥50% and 5-50% expectation of lung cancer on biopsy, respectively. Estimates of the prevalence
of one or more non-calcified nodules on initial screening CT include 23.3% in New York,4
26.3% in Japan,6 43% in Germany,3 and 51% in Minnesota.8Most nodules seen on an initial
screening CT are benign. In agreement with Swenson et al.,202,416 of 2,497 (96.8%) non-
calcified lung nodules seen on our initial CT showed no change, partial or complete resolution,
or calcification, when re-examined one year later, a behavior implying benign etiology.
The appearance of new nodules on repeat CT is another property of screening that complicates
management. In our study, 339 non-calcified nodules, not visible on the initial CT, appeared in
256 of 3,423 subjects on repeat CT, representing a 7.5% one-year risk of new nodule.
Potential harms from false positive nodules include financial and emotional costs, as well as
morbidity and mortality, associated with diagnostic intervention. We documented 737 diagnostic
imaging studies (CT, PET, or PET-CT) during the first year of follow-up in 628 of 1,255
(50.0%) subjects with low suspicion nodule. In the subset with only small (<0.5 cm) low
suspicion nodules, we documented 357 studies in 309 of 768 (40.2%) subjects.
Twenty-eight (34%) of 82 subjects with thoracotomy or VATS procedures for known or
suspected lung cancer ended in a non-cancer diagnosis, a result somewhat better than typical
practice, where 50% of thoracic surgical procedures to exclude malignancy in a lung nodule do
not find cancer.23, 24 Even after taking account of subjects who obtained thoracotomy or VATS
against the primary recommendation of study clinicians (Table 3), the frequency of resection for
benign nodules, as observed under our protocol, is higher than generally desired. Because the
three-year follow-up was not yet complete, our analysis may under-estimate the true frequency
of thoracotomy or VATS ending in non-cancer diagnoses.
In 3 of 28 instances (Table 3) of lung resection for benign nodule, a study pulmonologist (DOW)
recommended the procedure, triggered, in two instances, by falsely positive PET and, in the third
instance, by appearance of a new nodule on repeat CT. In 8 instances, subjects elected lung
resection, despite the study pulmonologist’s primary recommendation in favor of continued
observation with serial imaging. The remaining 17 subjects did not consult with the study
pulmonologist before accepting lung resection. Fourteen of 17 had lung resection after the initial
screening. When characterized according to our criteria for lung cancer suspicion and the
I-ELCAP diagnostic algorithm,15 we found 3 subjects with moderate-high lung cancer suspicion
who were I-ELCAP qualified for immediate biopsy, 7 subjects with moderate-high lung cancer
suspicion who were I-ELCAP qualified for 3-month CT, and 4 subjects with low cancer
suspicion who were I-ELCAP qualified for repeat CT screening in one year. Therefore, our
results show a high frequency of thoracotomy or VATS without cancer and an apparent
community bias toward aggressive intervention with biopsy for persons with indeterminate lung
nodule. Observing 12% of 522 subjects having a biopsy within one year of a positive screening
CT, Pinsky et al. also describe an apparent community bias toward biopsy.17These results argue
for strict adherence to diagnostic guidelines, in combination with informed decision making,
when managing persons with nodules detected on screening CT. Although validated evidence-
based guidelines are lacking, consensus guidelines are evolving to provide a framework for
managing findings detected on screening CT.4, 8, 15, 21
Forty (50%) of 80 subjects with primary lung cancer diagnosed within 3 years of initial CT were
stage I non-small cell lung cancer (Table 4). Though representing a higher percentage of early
stage disease when compared to the general population,1the stage distribution we observed is
less favorable than that reported by other investigators,3-8, 14, 15, but similar to the 53% value
reported by the Lung Cancer Screening Research Group.25Potential explanations include: 1)
selection factors favoring enrollment of minimally symptomatic as opposed to completely
asymptomatic at-risk subjects and 2) variable practices with respect to diagnostic intervention
We present results from the largest single-institution study of CT lung cancer screening in
current and ex-cigarette smokers. Our results include detailed information about diagnostic
imaging studies and invasive procedures that emanate from CT screening.
CT detects many indeterminate lung nodules, as well as early stage lung cancer. Diagnostic
imaging studies and invasive procedures associated with CT screening incur costs, health risks,
and anxiety that adversely affect quality of life. Our results indicate a tendency, in our
community, toward overly aggressive diagnostic evaluation, including thoracotomy and VATS
lung resection of CT screen-detected lung nodules. These results underscore the importance of
adhering to diagnostic algorithms for managing CT screen-detected nodules.
1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA-Cancer J Clin 2008;58:71-96.
2. Smith RA, Cokkinides V, Eyre HJ. Cancer screening in the United States, 2007: a review
of current guidelines, practices, and prospects. CA-Cancer J Clin 2007;57:90-104.
3. Diederich S, Wormanns D, Semik M, et al. Screening for early lung cancer with low-dose
spiral CT: prevalence in 817 asymptomatic smokers. Radiology 2002;222:773-81.
4. Henschke CI, McCauley DI, Yankelevitz DF, et al. Early Lung Cancer Action Project:
overall design and findings from baseline screening. Lancet 1999;354:99-105.
5. Kaneko M, Eguchi K, Ohmatsu H, et al. Peripheral lung cancer: screening and detection
with low-dose spiral CT versus radiography. Radiology 1996;201:798-802.
6. Nawa T, Nakagawa T, Kusano S, Kawasaki Y, Sugawara Y, Nakata H. Lung cancer
screening using low-dose spiral CT: results of baseline and 1-year follow-up studies. Chest
7. Sone S, Takashima S, Li F, et al. Mass screening for lung cancer with mobile spiral
computed tomography scanner. Lancet 1998;351:1242-5.
8. Swensen SJ, Jett JR, Sloan JA, et al. Screening for lung cancer with low-dose spiral
computed tomography. Am J Resp Crit Care 2002;165:508-13.
9. Black WC. Computed tomography screening for lung cancer: Review of screening
principles and update on current status. Cancer 2007;110:2370-84.
10. NLST: National Lung Screening Trial. (Accessed February 13, 2008, at
11. Blanchon T, Brechot J-M, Grenier PA, et al. Baseline results of the Depiscan study: a
French randomized pilot trial of lung cancer screening comparing low dose CT scan
(LDCT) and chest X-ray (CXR). Lung Cancer 2007;58:50-8.
12. Infante M, Lutman FR, Cavuto S, et al. Lung cancer screening with spiral CT: Baseline
results of the randomized DANTE trial. Lung Cancer 2008;59:355-63.
13. van Iersel CA, de Koning HJ, Draisma G, et al. Risk-based selection from the general
population in a screening trial: selection criteria, recruitment and power for the Dutch-
Belgian randomised lung cancer multi-slice CT screening trial (NELSON). Int J Cancer
14. Bach PB, Jett JR, Pastorino U, Tockman MS, Swensen SJ, Begg CB. Computed
tomography screening and lung cancer outcomes. JAMA 2007;297:953-61.
15. International Early Lung Cancer Action Program Investigators, Henschke CI, Yankelevitz
DF, et al. Survival of patients with stage I lung cancer detected on CT screening. New Engl
J Med 2006;355:1763-71.
16. Welch HG, Woloshin S, Schwartz LM, et al. Overstating the evidence for lung cancer
screening: the International Early Lung Cancer Action Program (I-ELCAP) study. Arch
Intern Med 2007;167:2289-95.
17. Pinsky PF, Marcus PM, Kramer BS, et al. Diagnostic procedures after a positive spiral
computed tomography lung carcinoma screen. Cancer 2005;103:157-63.
18. Lung function testing: selection of reference values and interpretative strategies. American
Thoracic Society. Am Rev Respir Dis 1991;144:1202-18.
19. Ferguson GT, Enright PL, Buist AS, Higgins MW. Office spirometry for lung health
assessment in adults: A consensus statement from the National Lung Health Education
Program. Chest 2000;117:1146-61.
20. Swensen SJ, Jett JR, Hartman TE, et al. Lung cancer screening with CT: Mayo Clinic
experience. Radiology 2003;226:756-61.
21. MacMahon H, Austin JHM, Gamsu G, et al. Guidelines for management of small
pulmonary nodules detected on CT scans: a statement from the Fleischner Society.
22. Bach PB, Kattan MW, Thornquist MD, et al. Variations in lung cancer risk among
smokers. J Natl Cancer Inst 2003;95:470-8.
23. Bernard A. Resection of pulmonary nodules using video-assisted thoracic surgery. The
Thorax Group. Ann Thorac Surg 1996;61:202-4; discussion 4-5.
24. Mack MJ, Hazelrigg SR, Landreneau RJ, Acuff TE. Thoracoscopy for the diagnosis of the
indeterminate solitary pulmonary nodule. Ann Thorac Surg 1993;56:825-30; discussion 30-
25. Gohagan J, Marcus P, Fagerstrom R, Pinsky P, Kramer B, Prorok P. Baseline findings of a
randomized feasibility trial of lung cancer screening with spiral CT vs chest radiograph:
The Lung Screening Study of the National Cancer Institute. Chest 2004;126:114-21.
Table 1: Subjects screened with helical CT, entry characteristics
Enrollment age (years)
60-69 1,201 33.0
Cigarette smoking status
current smoker 2,192 60.2
Cigarette dose intensity
1. Doctor diagnosis of chronic bronchitis, emphysema, or asthma
2. Hierarchical mutually exclusive categories based on self-reported history of cancer (other
than non-melanoma skin cancer) in parent, sibling, or half-sibling. Family history
information is missing in 20 subjects.
3. No airflow obstruction = FEV1/FVC ≥ 70 percent; GOLD I = FEV1/FVC < 70 and FEV1
≥ 80 percent predicted; GOLD II = FEV1/FVC < 70, FEV1 < 80 percent predicted, and
FEV1 ≥ 50 percent predicted; GOLD III-IV = FEV1/FVC < 70 and FEV1 < 50 percent
predicted. Airflow obstruction is missing in two subjects.
Table 2: Number of initial CT screenings, subsequent diagnostic imaging studies, and repeat CT
screenings, according to reason for referral, level of lung cancer suspicion, and diameter of the
largest non-calcified lung nodule
Initial or repeat CT screening result
Any suspicious nodule
high or moderate suspicion
182 257 206
largest nodule ≥ 0.5 cm
largest nodule < 0.5 cm
Lymph node or airway abnormality4
Significant incidental finding82 19 50
Any reason1,6081,141 1,506
1 N=3,642 subjects had an initial CT screening
2. Includes chest CT, PET, or PET-CT completed between initial screening and repeat
screening or within 365 days of initial screening, for subjects without repeat screening
3. N=3,423 subjects had a repeat CT screening
4. Thoracic lymph node enlargement and/or central airway mass, filling defect, or occlusion
in the absence of non-calcified lung nodules
Table 3: Thoracotomy or video-assisted thoracoscopy (VATS) in the setting of CT lung cancer
Thoracotomy or VATS
Clinical outcome N=54N=28 p-value3
thoracoscopic biopsy of hilar mass
video-assisted thoracoscopy (VAT)
Role of clinical investigator
seen by clinician, procedure recommended
seen by clinician, procedure not recommended
not seen by clinician
primary lung cancer
non-small cell carcinoma
small cell carcinoma
intra-pulmonary lymph node
1. Thoracotomy or VATS for primary lung cancer diagnosed within two years of a repeat
screening or, for subjects without repeat screening, within three years of an initial screening
2. Medical referral for any abnormality on an initial or repeat screening and thoracotomy or
VATS to exclude malignant lung nodule (completed within two years of a repeat screening
or, for subjects without repeat screening, within three years of an initial screening) with
resultant diagnosis other than cancer
3. Statistical significance (exact test) of the difference between the group with primary lung
cancer and the group with non-cancer diagnosis
Table 4: Primary lung cancer events1 in the setting of CT lung cancer screening
Tumor seen on initial
Small cell lung cancer
Non-small cell lung cancer
1. Primary lung cancer diagnosed within two years of a repeat screening or, for subjects
without repeat screening, within three years of an initial screening
2. Includes two subjects without a referral from either the initial or repeat CT screening
3. Includes one subject without a referral from either the initial or repeat CT screening
The Pittsburgh Lung Screening Study (PLuSS): Outcomes within 3 years of a first CT
David O. Wilson MD,MPH , Joel L. Weissfeld MD, MPH , Carl R. Fuhrman MD ,
Stephen N. Fisher MD , Paula Balogh CRNP, Rodney J. Landreneau MD,
James D. Luketich MD, andJill M. Siegfried PhD
ONLINE DATA SUPPLEMENT
Appendix Table 1: Summary nodule interpretation of lung cancer screening CT: Defining characteristics and follow-up
InterpretationDefining characteristic (initial CT) Defining characteristic (repeat CT)
High or moderate
Any 1.0+ cm or any spiculated 0.5-0.9
cm non-calcified lung nodule2
Any non-calcified lung nodule first
appearing on repeat CT or showing
suspicious change between baseline and
Low lung cancer
Any non-calcified lung nodule, but none
1.0+ cm and none 0.5-0.9 cm and
One or more non-calcified lung nodules,
all stable between baseline and repeat
1. Distinction between moderate and high suspicion categories based on subjective radiological criteria.
2. Nodule size based on the average of two orthogonal diameter measurements in the axial plane.
29 Download full-text
Table for web supplement: Cross-tabulation of initial CT versus repeat CT screening result.
Initial CT screening result
Any reason for referral
Any suspicious nodule
high or moderate suspicion
largest nodule ≥ 0.5 cm
largest nodule < 0.5 cm
Lymph node or airway abnormality 
Significant incidental finding
No reason for referral
Note: The table shows column percents for the numbers with repeat CT and row percents for the numbers with specified reasons for
6.0 1,226 35.8
7.6 1,089 72.8
7.9 1,079 78.5
3,642 3,423 94.0 1,506 44.0 1,450 42.4
1,608 1,495 93.0 1,239 82.9 1,219 81.5
1,477 1,374 93.0 1,209 88.0 1,201 87.4
222171 77.0134 78.4
40 13 32.5
182158 86.8122 77.2
1,255 1,203 95.9 1,075 89.4 1,070 88.9
487461 94.7419 90.9
768742 96.6656 88.4
49 43 87.8
82 78 95.1
2,034 1,928 94.8267 13.8
12 92.36 46.2
Repeat CT screening reason for referral
largest ≥ 0.5
largest < 0.5
referral on repeat CT. The latter calculations express percentages in terms of the number with repeat CT.
1. Thoracic lymph node enlargement and/or central airway mass, filling defect, or occlusion in the absence of non-calcified lung