Early Lung Cancer Screening:
An Update of the Current Evidence
Simon Martel, MD
IUCPQ
Quebec, Canada
No conflict of interest
Lung Cancer Epidemiology
• Most frequent cause of cancer death
• In 2020 = 5th cause of death
• In 2010 (Canada) = 11200 deaths in men and 9400
deaths in women (27% of all cancer deaths)
• Overall survival at 5 years around 15%
• 90% of cases attributable to smoking and 50% of
new cases in former smokers
Fundamentals of Screening
• The purpose of screening is to detect a disease
at a stage when cure or control is possible
• At risk population for a specific disease is
submitted to a test to identify asymptomatic
persons having the disease
• Persons with a positive result will then be
evaluated to determine whether they actually
have the disease
Fundamentals of Screening
• Characteristics of a good screening test and
program:
– Reasonable sensitivity and specificity
– Accessible with a low cost
– Low associated morbidity
• There should be an effective treatment at an
early stage of the disease
Screening Bias
Patz EF et al. New Eng J Med 2000
Screening Bias
Patz EF et al. New Eng J Med 2000
Screening Bias
Black WC. Cancer 2007
Fundamentals of Screening
• A good lung cancer screening program should
reduce lung cancer mortality and overall
mortality in the screened group compared to
the unscreened group
1950-1990
• Randomised and non randomised controlled trials:
–
–
–
–
–
–
–
John Hopkins Lung Project
Memorial Sloan Kettering Lung Project
Mayo Lung Project
Czechoslovakian Study
North London Cancer Study
Erfurt County Study
Kaiser Permanente Study
• Chest radiograph ± sputum cytology every 4 to 12 months
compared to less frequent or no screening over 3 to 16 years
• 52000 subjects in intervention groups and 48000 in control
groups
1950-1990
• Intervention groups:
– More lung cancers
– More early stage lung cancers
– More resectable lung cancers
• No reduction in lung cancer mortality
Recommendations
Bach BP et al. Chest 2007
Are we done with chest X-ray
in lung cancer screening?
J Natl Cancer Inst 2005
Radiation
« Persons at risk for repeated radiation exposure,
such as workers in health care and the nuclear
industry, are typically monitored and restricted
to effective doses of 100 mSv every 5 years (i.e.
20 mSv per year), with a maximum of 50 mSv
allowed in any given year. »
Fazel R et al. New Eng J Med 2009
Radiation
Procedure
Effective dose (mSv)
Chest radiograph (PA view)
0.02
Radiograph of abdomen
0.7
Mammography
0.4
Nuclear bone imaging
6.3
Chest CT
7
Abdomen CT
8
Chest angio-CT
15
Diagnostic cardiac cath.
15
Radiation
• Low dose CT
Baldwin DR et al. Thorax 2011
CT lung cancer screening
Black WC. Cancer 2007
CT lung cancer screening
Black WC. Cancer 2007
CT lung cancer screening
Black WC. Cancer 2007
CT lung cancer screening
• What have we learned from these studies?
– Management of small pulmonary nodules
– CT can detect early stage lung cancer
– Excellent survival in a majority of screened
cases
– More epidemiology
– More and more adenocarcinomas…
– Overdiagnosis? Slow growing tumors?
Follow-up of nodules
MacMahon H et al. Radiology 2005
Thorax 2011
Early stage detection
New Eng J Med 2006
Overdiagnosis?
Growth Model of Lung Cancer
Bach BP et al. Chest 2007
CT Randomised Controlled Trials
• DEPISCAN (France)
• ITALUNG trial (Italy)
– 3 206 participants
– Active and former smokers 55-69 years old
– Chest CT annually for 4 years vs no screening
• NELSON Trial (Dutch-Belgian)
– 15 248 participants (2004-2006)
– Chest CT at 0, 1 and 3 years vs no screening
– Active and former smokers 50-75 years old
CT Randomised Controlled Trials
• DANTE Trial (Italy)
–
–
–
–
2472 participants, male, 60-75 years old (2001-2006)
Chest X-ray and sputum cytology at baseline (all)
Chest CT at 0, 1, 2, 3 and 4 years vs annual medical visit
Active and former smokers of at least 20 pack-years
DANTE trial
Infante M et al. Am J Respir Crit Care Med 2009
CT Randomised Controlled Trials
• NLST (USA)
– 53 456 participants (2002-2004)
– Chest CT vs radiograph at 0, 1 and 2 years
– Active and former smokers 55 to 74 years-old
• Results
– 20.3% reduction in lung cancer mortality (354 deaths vs
442 deaths)
– All-cause mortality lower by 7% in the CT group
NLST Participants
Total
M/F
Age (55 – 74)
Race W / B / A
Cur / For Smokers
Quit (4 / 10 / 15)
CT
26723
X-ray
26733
59 / 41 %
43 / 30 / 18 / 9 %
91 / 4 / 2 %
59 / 41 %
43 / 30 / 18 / 9 %
91 / 4 / 2 %
48 / 52 %
15 / 17 / 20 %
48 / 52 %
15 / 17 / 19 %
Pan-Canadian Early Detection of
Lung Cancer Study
• Validate a low cost risk modeling to select a
population with a higher risk of lung cancer
• Evaluate the add-on impact of spirometry, blood
biomarkers and AFB in a screening strategy
• Evaluate the impact of the screening modalities on
the quality of life
• Evaluate the cost of implementing a lung cancer
screening in Canada
Pan-Canadian Early Detection of
Lung Cancer Study
3000
2500
Actual
Projected
Enrolled N=2533
AFB = 1252
2000
1500
66 lung cancers confirmed
1000
500
0
Oct-08
Feb-09
Jun-09
Oct-09
Feb-10
Jun-10
Oct-10
478 Normal CT Scans at Baseline (20%)
Percentage of Normal CT Scans at Baseline per Site
Halifax
Quebec
Ottawa
Hamilton
% normal scans
Toronto
Calgary
Vancouver
0
5
10
15
20
25
30
35
40
Pan-Canadian Early Detection of
Lung Cancer Study
• Nodules of course
• Other findings:
–
–
–
–
–
–
–
Kydney cyst or mass
Adrenal nodule
Interstitial lung disease
Coronary calcifications
Thoracic aorta aneurism
Thyroid nodule
…
Conclusions
• We are not ready for lung cancer screening
• Low dose CT might be an interesting tool but
many questions to answer
–
–
–
–
–
Lung cancer mortality reduction?
Overall mortality reduction?
Magnitude of overdiagnosis?
Morbidity associated with screening?
Cost of this type of screening?
• SMOKING CESSATION is still a priority!
Screening Bias
Black WC. Cancer 2007
1950-1990
Manser RL et al. Thorax 2003
1950-1990
Manser RL et al. Thorax 2003
1950-1990
Manser RL et al. Thorax 2003
Radiation
Brenner DJ et al. New Eng J Med 2006
Radiation
Brenner DJ et al. New Eng J Med 2006
New Engl J Med 2009
Coûts-Bénéfices?
Am J Respir Crit Care Med 2008
Coûts-Bénéfices?
• Étude PLuSS
–
–
–
–
3 642 sujets avec TDM de base
3 423 sujets avec TDM répété à 1 an
1 477 sujets avec nodules au TDM initial
821 sujets ont eu une ou des études
supplémentaires (TDM et/ou TEP) avant le
TDM à 1 an
Coûts-Bénéfices?
Wilson DO et al. Am J Respir Crit Care Med 2008
Coûts-Bénéfices?
Bach PB et al. Chest 2007
Overdiagnosis?
Follow-up of nodules
FU CT
FU CT
FU CT
Solid <5mm
12 months
24 months
Nonsolid <8mm
12 months
24 months
Any size semisolid
3 months
12 months
24 months
Solid 5-9 mm/nonsolid 810mm
3 months
12 months
24 months
Any lesions ≥ 10mm
immediate assessment for
either investigation or FU
2-3 months
12 months
24 months
Lung Cancer Risk Assessment Model
•
•
•
•
•
•
•
Age
Smoking history
History of COPD (self-reported)
Chest X-ray in last 3 years
Family history
Education
Body mass index
M Tammemagi & PLCO Study
Group
66 Confirmed Cancers
CA at
baseline
1
Invest.
2+
Invest.
CA on
Visit 2
CA on
AFB
Normal
Baseline
Total
(no nods)
Vancouver
3
6
Calgary
1
1
Toronto
2
3
2
1
Hamilton
10
2
1
1*
Ottawa
7
1
Quebec
6
2
1
Halifax
1
4
2
Total
30
19
9
4
3
65
46%
29%
14%
6%
5%
plus 1
incidence Case
*Normal at baseline
3
1*
1
13
2
8
1*
2
15
8
1
2
12
7