4Clinical Stages and Survival/Prognosis 31%Stade III38%Stade IV24%Stade I7%Stade II31. Non-Small Cell Lung Cancer: Stages at PresentationNSCLC patients typically present with advanced disease. Approximately one third of NSCLC patients present with early localized disease amenable to surgical treatment.Fry, Cancer 1999;86:Groome, IASLC Lung Cancer staging project, JTO 2007;2:
5Screening for Lung Cancer What Tools ? Sputum cytologyChest X-rayChest CTAutofluorescence bronchoscopyMarkers (serum, exhaled air, urine…)
7The PLCO (Prostate, Lung, Colorectal and Ovarian) trial 3 annual chest X-rays (n=77445) vs usual care (n=77456)55-74 yrs, 45% never smokersNumber of lung cancers1696vs 1620Oken, JAMA 2011;306(17):
8The PLCO (Prostate, Lung, Colorectal and Ovarian) trial 3 annual chest X-rays (n=77445) vs usual care (n=77456)55-74 yrs, 45% never smokersDeaths from lung cancer1213vs 1230Oken, JAMA. 2011;306(17):
9Screening for Lung Cancer What Tools ? Sputum cytologyChest X-rayChest CTAutofluorescence bronchoscopyMarkers (serum, exhaled air, urine…)
10Lung Cancer Screening with CT Screening « window »Diameter2 mm8 mm40 mm200mmNb of cells4.1063.10833.1094.1012Bach, ACCP guidelines, Chest 2007;132:69S-77S
11Computed Tomography (CT) of the Chest RoutineLow-dose938mGy/cm15.9 mSv88mGy/cm1.5 mSvComputed Tomography (CT) of the Chest -- Routine (Left) versus Low Dose (Right). The surveillance of small pulmonary nodules is a common indication for chest CT, and several protocols can be used for these studies. Routine chest CT (Panel A) is associated with a radiation dose to the patient that is 10 times that of low-dose chest CT (Panel B) (dose-length product, 938 mGy per centimeter vs. 88 mGy per centimeter; effective dose, 15.9 mSv vs. 1.5 mSv) -- yet each shows the small pulmonary nodule equally well (Panels A and B, arrows). The pulmonary parenchyma and upper abdomen are better visualized on the higher-dose routine scan (Panels A and C, respectively) than the low-dose scan (Panels B and D, respectively), but these areas are irrelevant to follow-up of a small pulmonary nodule. A recent survey of radiologists who perform chest CT showed that low-dose CT was not routinely used for examinations performed solely for the purpose of nodule follow-up and that most radiologists were unaware of the CT settings used for initial versus follow-up CT.1 Standardization of CT protocols could result in substantial reduction in patients' radiation doses without loss of diagnostic accuracy. Images courtesy of Dr. Michael J. Flynn, Department of Radiology, Henry Ford Health Systems.Smith-Bindman, N Engl J Med 2010;
12Screening with Low-dose CT It works ?31,567 subjects( )481 lung cancersdetected85% stage I(n=412)ELCAP, NEJM 2006;355:
13National Lung Cancer Screening Trial (NLST) Fumeurs Anciens fumeurs≥ 30 PA Age 55-7440,000 PLCO10,000 ACRINScanner low doseRadiographieYears12RANDOMISATONNLST, NEJM 2011; 365(5):
14NLST: Trial discontinuation in oct. 2010 ! 55 to 74 yrs, > 30P-Y, active or stop<15 yrsn« Positive »(diam>=4mm)Lung cancersLung cancer deathsRiskreductionLow-dose CT26.45518.146(68.5%)1.060346(1.3%)20,0%Chest X-ray26.2325.043(19.2%)941425(1.6%)NNS to prevent 1 lung cancer death = 320…NLST, NEJM 2011; 365(5):
15NLST: Highly selected population Probably healthier vs. base population< 65 years73% vs 65% in the base populationLess current smokers48% vs 57%Better educated6% with less than a high school education vs 21%NLST, JNCI 2010
17NLST: Magic Compliance NLST : Compliance > 90%Women adherence to mammography screening higher ifYoungerHigher educationLived in an area with a higher percentage of mammography facilitiesPhilips KA, Health Serv Res Apr;33(1):29-53.
18Cause of Death (CT group) n%Reduction vs control groupLung cancer42722.9%20% (6.8 – 26.7, p <0.004)Other Neoplasm41622.3%3.2%(p = 0.28)Cardiovasc. Illness48626.1%Respiratory illness1759.4%Complication of medical or surgical care120.6%Other34918.7%All18656.2% (1.2 – 13.6%, p = 0.02NLST, NEJM 2011; 365(5):
19Deaths from lung cancer NLST: Trial discontinuation in oct !Deaths from lung cancerbut…« NCI is not yet recommending such screening »NLST, NEJM 2011; 365(5):
20Unanswered QuestionsHow to diminish the false positive rate ?
21The NELSON trial (Nederlands-Leuvens Longkanker Screenings Onderzoek) Automated volumetric measurment for non-calcified nodulesNPV of diagnostic strategy at 1 yr = 99.9%4,147mm3van Klaveren, NEJM 2009, 361:123
22Unanswered Questions How to diminish false positive rate? Should the ongoing trials go on?...
24PISA 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 poolingDiscouragement of opportunistic screening outside clinical trials !de Koning, ECCO-ESMO meeting, Sept. 2011
25Unanswered Questions How to diminish false positive rate? Should the ongoing trials go on?...How many screen rounds?
26How many screen rounds?Lung cancer was diagnosed frequently after the third low-dose CT screeningThis observation suggests that continuing to screen high-risk individuals annually will provide a net benefit.
27Unanswered Questions How to diminish false positive rate? Should the ongoing trials go on?...How many screen rounds?False reassurance (license to smoke)?...
28Screening with Low-dose CT It works ?31,567 subjects( )481 lung cancersdetected85% stage I(n=412)Negative CT ?Keep smoking !Positive CT ?Keep smoking !(we can cure your cancer)IELCAPI, NEJM 2006;355:
32Blood is the issueNSLT collected > blood samples
33Effects of Smoking Cessation on the Risk of Lung Cancer Quit at age 50:risk reduction about 66%Peto, BMJ 2000,321:323
341 month of tobacco consumption 2.5 months of nicotine substitutes Deal ?1 CT scan (138 €)=27 packs of cigarettes1 month of tobacco consumption2.5 months of nicotine substitutes
35Dépistage à l’échelon individuel Séminaire de réflexion sur la littérature récente concernant le dépistage scanographique du Cancer broncho-pulmonaire.17-18 février 2012 – GOLF et IFCTDépistage à l’échelon individuelAprès information sur les bénéfices et risques encourusSujets âgés de 55 à 74ans et ont fumés plus de 30PAInformation sur sevrage tabagique impératifGOLF :Fabrice BarlésiEtienne LemariéGOLF :Fabrice BarlésiEtienne Lemarié