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Early Lung Cancer Screening:An Update of the Current Evidence
Simon Martel, MD
IUCPQ
Quebec, Canada
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No conflict of interest
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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
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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
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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
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Screening Bias
Patz EF et al. New Eng J Med 2000
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Screening Bias
Patz EF et al. New Eng J Med 2000
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Screening Bias
Black WC. Cancer 2007
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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
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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
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1950-1990
• Intervention groups:– More lung cancers
– More early stage lung cancers
– More resectable lung cancers
• No reduction in lung cancer mortality
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Recommendations
Bach BP et al. Chest 2007
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Are we done with chest X-ray in lung cancer screening?
J Natl Cancer Inst 2005
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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
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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
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Radiation• Low dose CT
Baldwin DR et al. Thorax 2011
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CT lung cancer screening
Black WC. Cancer 2007
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CT lung cancer screening
Black WC. Cancer 2007
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CT lung cancer screening
Black WC. Cancer 2007
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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?
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Follow-up of nodules
MacMahon H et al. Radiology 2005
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Thorax 2011
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Early stage detection
New Eng J Med 2006
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Overdiagnosis?
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Growth Model of Lung Cancer
Bach BP et al. Chest 2007
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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
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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
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DANTE trial
Infante M et al. Am J Respir Crit Care Med 2009
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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
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NLST Participants
CT X-ray
Total 26723 26733
M / F 59 / 41 % 59 / 41 %
Age (55 – 74) 43 / 30 / 18 / 9 % 43 / 30 / 18 / 9 %
Race W / B / A 91 / 4 / 2 % 91 / 4 / 2 %
Cur / For Smokers 48 / 52 % 48 / 52 %
Quit (4 / 10 / 15) 15 / 17 / 20 % 15 / 17 / 19 %
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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
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Pan-Canadian Early Detection of Lung Cancer Study
0
500
1000
1500
2000
2500
3000
Oct-08 Feb-09 Jun-09 Oct-09 Feb-10 Jun-10 Oct-10
Actual
Projected
Enrolled N=2533
AFB = 1252
66 lung cancers confirmed
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Percentage of Normal CT Scans at Baseline per Site
0 5 10 15 20 25 30 35 40
Vancouver
Calgary
Toronto
Hamilton
Ottawa
Quebec
Halifax
% normal scans
478 Normal CT Scans at Baseline (20%)
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• Nodules of course
• Other findings:– Kydney cyst or mass
– Adrenal nodule
– Interstitial lung disease
– Coronary calcifications
– Thoracic aorta aneurism
– Thyroid nodule
– …
Pan-Canadian Early Detection of Lung Cancer Study
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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!
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Screening Bias
Black WC. Cancer 2007
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1950-1990
Manser RL et al. Thorax 2003
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1950-1990
Manser RL et al. Thorax 2003
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1950-1990
Manser RL et al. Thorax 2003
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Radiation
Brenner DJ et al. New Eng J Med 2006
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Radiation
Brenner DJ et al. New Eng J Med 2006
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New Engl J Med 2009
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Coûts-Bénéfices?
Am J Respir Crit Care Med 2008
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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
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Coûts-Bénéfices?
Wilson DO et al. Am J Respir Crit Care Med 2008
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Coûts-Bénéfices?
Bach PB et al. Chest 2007
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Overdiagnosis?
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Follow-up of nodulesFU 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 8-10mm
3 months 12 months 24 months
Any lesions ≥ 10mm immediate assessment for either investigation or FU
2-3 months 12 months 24 months
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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
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66 Confirmed Cancers
Vancouver 3 6 3 1* 1 13
Calgary 1 1 2
Toronto 2 3 2 1 8
Hamilton 10 2 1 1* 1* 2 15
Ottawa 7 1 8
Quebec 6 2 1 1 2 12
Halifax 1 4 2 7
Total 3046%
1929%
914%
46%
35%
65plus 1 incidence Case
*Normal at baseline
CA at baseline
1 Invest.
2+ Invest.
CA on Visit 2
CA on AFB
Normal
Baseline(no nods)
Total