1ers MACA – Ajaccio – 10 mai 2012
Benjamin Besse,
Philippe Girard
Cancer Incidence and Mortality (world)
LUNG CANCER
Incidence = 1,600,000/yr
Mortality = 1,370,000/yr
 Lethality ≈ 85%
Screening: why ?
• Goal: cancer mortality reduction
• Detect asymptomatic cancers
• Asymptomatic cancers = better prognosis (?)
Clinical Stages and Survival/Prognosis
7%
Stade II
31%
Stade III
24%
Stade I
38%
Stade
IV
Fry, Cancer 1999;86:1867-76
Groome, IASLC Lung Cancer staging project, JTO 2007;2:694-705
Screening for Lung Cancer
What Tools ?
• Sputum cytology
• Chest X-ray
• Chest CT
• Autofluorescence bronchoscopy
• Markers (serum, exhaled air, urine…)
Lung Cancer Screening Tools
• Sputum Cytology
• Chest X-ray
Bach, ACCP guidelines, Chest 2007;132:69S-77S
The PLCO (Prostate, Lung, Colorectal and Ovarian) trial
• 3 annual chest X-rays (n=77445) vs usual care (n=77456)
• 55-74 yrs, 45% never smokers
Number of lung cancers
1696
vs 1620
Oken, JAMA 2011;306(17):1865-1873
The PLCO (Prostate, Lung, Colorectal and Ovarian) trial
• 3 annual chest X-rays (n=77445) vs usual care (n=77456)
• 55-74 yrs, 45% never smokers
Deaths from lung cancer
1213
vs 1230
Oken, JAMA. 2011;306(17):1865-1873
Screening for Lung Cancer
What Tools ?
• Sputum cytology
• Chest X-ray
• Chest CT
• Autofluorescence bronchoscopy
• Markers (serum, exhaled air, urine…)
Lung Cancer Screening with CT
Screening « window »
Diameter
2
mm
8 mm
40 mm
200mm
Nb of cells
4.106
3.108
33.109
4.1012
Bach, ACCP guidelines, Chest 2007;132:69S-77S
Computed Tomography (CT) of the Chest
Routine
Low-dose
938mGy/cm
88mGy/cm
15.9 mSv
1.5 mSv
Smith-Bindman, N Engl J Med 2010;10.1056
Screening with Low-dose CT
It works ?
• 31,567 subjects
(1993-2005)
• 481 lung cancers
detected
• 85% stage I
(n=412)
ELCAP, NEJM 2006;355:1763-71
National Lung Cancer
Screening Trial (NLST)
40,000
PLCO
Fumeurs
Anciens fumeurs
≥ 30 PA
Age 55-74
10,000
ACRIN
R
A
N
D
O
M
I
S
A
T
I
O
N
Scanner low dose
Radiographie
0
1
2
Years
NLST, NEJM 2011; 365(5):395-409
NLST: Trial discontinuation in oct. 2010 !
55 to 74 yrs, > 30P-Y, active or stop<15 yrs
n
« Positive »
(diam>=4mm)
Low-dose
CT
26.455
18.146
(68.5%)
Lung
cancers
Lung
cancer
deaths
1.060
346
(1.3%)
Risk
reduction
20,0%
Chest X-ray 26.232
5.043
(19.2%)
941
425
(1.6%)
NNS to prevent 1 lung cancer death = 320…
NLST, NEJM 2011; 365(5):395-409
NLST: Highly selected population
• Probably healthier vs. base population
• < 65 years
– 73% vs 65% in the base population
• Less current smokers
– 48% vs 57%
• Better educated
– 6% with less than a high school education vs
21%
NLST, JNCI 2010
155 ponctions, 206 fibros, 297 chirurgies
270 cancers ! (4%)
NLST: Magic Compliance
• NLST : Compliance > 90%
• Women adherence to mammography
screening higher if
– Younger
– Higher education
– Lived in an area with a higher percentage of
mammography facilities
Philips KA, Health Serv Res. 1998 Apr;33(1):29-53.
Cause of Death (CT group)
n
%
Reduction
vs control group
Lung cancer
427
22.9%
20%
(6.8 – 26.7, p <0.004)
Other Neoplasm
416
22.3%
Cardiovasc. Illness
486
26.1%
Respiratory illness
175
9.4%
Complication of medical
or surgical care
12
0.6%
Other
349
18.7%
All
1865
3.2%
(p = 0.28)
6.2%
(1.2 – 13.6%, p = 0.02
NLST, NEJM 2011; 365(5):395-409
NLST: Trial discontinuation in oct. 2010 !
• Deaths from lung cancer
but…
« NCI is not yet recommending such screening »
NLST, NEJM 2011; 365(5):395-409
Unanswered Questions
• How to diminish the false positive rate ?
The NELSON trial
(Nederlands-Leuvens Longkanker Screenings Onderzoek)
 Automated volumetric measurment for non-calcified
nodules
4,147mm3
 NPV of diagnostic strategy at 1 yr = 99.9%
van Klaveren, NEJM 2009, 361:123
Unanswered Questions
• How to diminish false positive rate?
• Should the ongoing trials go on?...
European Screening Trials Overview
NELSON
DLCST
ITALUNG
LUSI
DANTE
MILD
4
5
4
5
5
10 or 5
Enrollement
15,464
4,104
3,206
3,551
2,472
3,581
Completed
Y
Y
Y
N
Y
N
Baseline
detection
0.9%
0.8%
1.5%
1.0%
2.2%
0.8%
Incidence
0.5%
0.6%
0.4%
-
0.5%
0.5%
Nr rounds
de Koning, ECCO-ESMO meeting, Sept. 2011
PISA position Statement (March 2011)
• 6 ongoing European trials have enrolled 32,000
subjects with about 150,000 person-years of follow-up
(approx. half of NLST)
• European trials continuation !
• Concrete plan for interim analyses and/or pooling
• Discouragement of opportunistic screening outside
clinical trials !
de Koning, ECCO-ESMO meeting, Sept. 2011
Unanswered Questions
• How to diminish false positive rate?
• Should the ongoing trials go on?...
• How many screen rounds?
How many screen rounds?
• Lung cancer was diagnosed frequently after the third
low-dose CT screening
• This observation suggests that continuing to screen
high-risk individuals annually will provide a net benefit.
Unanswered Questions
•
•
•
•
How to diminish false positive rate?
Should the ongoing trials go on?...
How many screen rounds?
False reassurance (license to smoke)?...
Screening with Low-dose CT
It works ?
Negative CT ?
Keep smoking !
• 31,567 subjects
(1993-2005)
Positive CT ?
Keep smoking !
(we can cure your cancer)
• 481 lung cancers
detected
• 85% stage I
(n=412)
IELCAPI, NEJM 2006;355:1763-71
Screening routine nightmare
McMullan and Cohen NEJM 2006, 354 (4): 397
Unanswered Questions
•
•
•
•
•
How to diminish false positive rate?
Should the ongoing trials go on?...
How many screen rounds?
False reassurance (license to smoke)?...
Where to go ?
Blood is the issue
• NSLT collected >100 000 blood samples
Effects of Smoking Cessation
on the Risk of Lung Cancer
• Quit at age 50:
risk reduction about 66%
Peto, BMJ 2000,321:323
Deal ?
1 CT scan (138 €)
=
27 packs of cigarettes
=
1 month of tobacco consumption
=
2.5 months of nicotine substitutes
Séminaire de réflexion sur la littérature récente
concernant le dépistage scanographique du
Cancer broncho-pulmonaire.
17-18 février 2012 – GOLF et IFCT
• Dépistage à l’échelon individuel
• Après information sur les bénéfices et
risques encourus
• Sujets âgés de 55 à 74ans et ont fumés
plus de 30PA
• Information sur sevrage tabagique
impératif