1. Early Lung Cancer Screening: An Update of the Current Evidence
Simon Martel, MD
IUCPQ
Quebec, Canada

2. No conflict of interest

3. Lung Cancer Epidemiology
Most frequent cause of cancer death
In 2020 = 5th cause of death
In 2010 (Canada) = 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

4. 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

5. 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

6. Screening Bias
Patz EF et al. New Eng J Med 2000

7. Screening Bias
Patz EF et al. New Eng J Med 2000

8. Screening Bias
Black WC. Cancer 2007

9. 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

10. 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 in control groups

11. 1950-1990 Intervention groups: No reduction in lung cancer mortality
More lung cancers
More early stage lung cancers
More resectable lung cancers
No reduction in lung cancer mortality

12. Recommendations
Bach BP et al. Chest 2007

13. Are we done with chest X-ray in lung cancer screening?
J Natl Cancer Inst 2005

14. 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

15. 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.

16. Radiation
Low dose CT
Baldwin DR et al. Thorax 2011

17. CT lung cancer screening
Black WC. Cancer 2007

18. CT lung cancer screening
Black WC. Cancer 2007

19. CT lung cancer screening
Black WC. Cancer 2007

20. 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?

21. Follow-up of nodules
MacMahon H et al. Radiology 2005

22. Thorax 2011

23. Early stage detection
New Eng J Med 2006

24. Overdiagnosis?

25. Growth Model of Lung Cancer
Bach BP et al. Chest 2007

26. CT Randomised Controlled Trials
DEPISCAN (France)
ITALUNG trial (Italy)
3 206 participants
Active and former smokers years old
Chest CT annually for 4 years vs no screening
NELSON Trial (Dutch-Belgian)
participants ( )
Chest CT at 0, 1 and 3 years vs no screening
Active and former smokers years old

27. CT Randomised Controlled Trials
DANTE Trial (Italy)
2472 participants, male, years old ( )
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

28. DANTE trial
Infante M et al. Am J Respir Crit Care Med 2009

29. CT Randomised Controlled Trials
NLST (USA)
participants ( )
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

30. NLST Participants CT X-ray Total 26723 26733 M / F 59 / 41 %
Age (55 – 74)
43 / 30 / 18 / 9 %
Race W / B / A
91 / 4 / 2 %
Cur / For Smokers
48 / 52 %
Quit (4 / 10 / 15)
15 / 17 / 20 %
15 / 17 / 19 %

31. 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

32. Pan-Canadian Early Detection of Lung Cancer Study
Enrolled N=2533
AFB = 1252
66 lung cancers confirmed

33. 478 Normal CT Scans at Baseline (20%)

34. 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 …

35. 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!

36. Screening Bias
Black WC. Cancer 2007

37.
Manser RL et al. Thorax 2003

38.
Manser RL et al. Thorax 2003

39.
Manser RL et al. Thorax 2003

40. Radiation
Brenner DJ et al. New Eng J Med 2006

41. Radiation
Brenner DJ et al. New Eng J Med 2006

42. New Engl J Med 2009

43. Coûts-Bénéfices?
Am J Respir Crit Care Med 2008

44. 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

45. Coûts-Bénéfices?
Wilson DO et al. Am J Respir Crit Care Med 2008

46. Coûts-Bénéfices?
Bach PB et al. Chest 2007

48. Overdiagnosis?

49. Follow-up of nodules FU CT Solid <5mm 12 months 24 months
Nonsolid <8mm
Any size semisolid
3 months
Solid 5-9 mm/nonsolid 8-10mm
Any lesions ≥ 10mm immediate assessment for either investigation or FU
2-3 months

50. 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

51. 66 Confirmed Cancers *Normal at baseline 1 Invest. 2+ Invest.
CA at baseline
1 Invest.
2+ Invest.
CA on Visit 2
CA on AFB
Normal
Baseline
(no nods)
Total
Vancouver 3 6 1* 1 13
Calgary 2
Toronto 8
Hamilton 10 15
Ottawa 7
Quebec 12
Halifax 4
Total 30
46% 19
29% 9
14% 4 6% 3 5% 65
plus 1 incidence Case
*Normal at baseline