Title: Early Lung Cancer Screening: An Update of the Current Evidence
1Early Lung Cancer ScreeningAn Update of the
Current Evidence
- Simon Martel, MD
- IUCPQ
- Quebec, Canada
2No conflict of interest
3Lung 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
4Fundamentals 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
5Fundamentals 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
6Screening Bias
Patz EF et al. New Eng J Med 2000
7Screening Bias
Patz EF et al. New Eng J Med 2000
8Screening Bias
Black WC. Cancer 2007
9Fundamentals 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
101950-1990
- 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
111950-1990
- Intervention groups
- More lung cancers
- More early stage lung cancers
- More resectable lung cancers
- No reduction in lung cancer mortality
12Recommendations
Bach BP et al. Chest 2007
13Are we done with chest X-ray in lung cancer
screening?
J Natl Cancer Inst 2005
14Radiation
- 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
15Radiation
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
16Radiation
Baldwin DR et al. Thorax 2011
17CT lung cancer screening
Black WC. Cancer 2007
18CT lung cancer screening
Black WC. Cancer 2007
19CT lung cancer screening
Black WC. Cancer 2007
20CT 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?
21Follow-up of nodules
MacMahon H et al. Radiology 2005
22Thorax 2011
23Early stage detection
New Eng J Med 2006
24Overdiagnosis?
25Growth Model of Lung Cancer
Bach BP et al. Chest 2007
26CT 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
27CT 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
28DANTE trial
Infante M et al. Am J Respir Crit Care Med 2009
29CT 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
30NLST 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
31Pan-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
32Pan-Canadian Early Detection of Lung Cancer Study
Enrolled N2533 AFB 1252 66 lung cancers
confirmed
33478 Normal CT Scans at Baseline (20)
34Pan-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
-
35Conclusions
- 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!
36Screening Bias
Black WC. Cancer 2007
371950-1990
Manser RL et al. Thorax 2003
381950-1990
Manser RL et al. Thorax 2003
391950-1990
Manser RL et al. Thorax 2003
40Radiation
Brenner DJ et al. New Eng J Med 2006
41Radiation
Brenner DJ et al. New Eng J Med 2006
42New Engl J Med 2009
43Coûts-Bénéfices?
Am J Respir Crit Care Med 2008
44Coûts-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
45Coûts-Bénéfices?
Wilson DO et al. Am J Respir Crit Care Med 2008
46Coûts-Bénéfices?
Bach PB et al. Chest 2007
47(No Transcript)
48Overdiagnosis?
49Follow-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
50Lung 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
5166 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