Early Lung Cancer Screening: An Update of the Current Evidence

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Early Lung Cancer ScreeningAn 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
Enrolled N2533 AFB 1252 66 lung cancers
confirmed
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478 Normal CT Scans at Baseline (20)
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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

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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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(No Transcript)
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Overdiagnosis?
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Follow-up of nodules
FU CT FU CT FU CT
Solid lt5mm 12 months 24 months
Nonsolid lt8mm 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
CA at baseline 1 Invest. 2 Invest. CA on Visit 2 CA on AFB Normal Baseline (no nods) Total
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 30 46 19 29 9 14 4 6 3 5 65 plus 1 incidence Case
Normal at baseline