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

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 %

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

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

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%)

• 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

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 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

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

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