Example of lung screening

Transcription

1 Justification of the use of CT for individual health assessment of asymptomatic people How to obtain evidence for IHA - Example of lung screening Mathias Prokop, MD PhD Professor of Radiology Radboud University Medical Center Nymegen, The Netherlands

2 Individual Health Assessment Why would people want it? Reassurance Exclude dangerous disease Early diagnosis Find dangerous disease early Early treatment Treat this disease while it is not too late Treat it while it is still relatively cheap

3 Individual Health Assessment Requires evidence Reassurance Exclude dangerous disease Early diagnosis Find dangerous disease early Early treatment Treat this disease while it is not too late Treat it while it is still relatively cheap

4 Individual Health Assessment Collateral damage Due to Radiation risk Harm of workup Complications due to workup Complications from unnecessary treatment Cost of workup and treatment from benign or indolent disease Aberle D et al. NEJM 2013;369:920

5 The Example of Lung Screening Why should we want to do it?

6 Lung Cancer How big is the problem? Epidemiology Leading cause of cancer death (28%) More than breast + prostate + colon + pancreas cancer Estimated increase in cancer rates by 2030: % Survival 5-year survival: lung cancer 15% compare: breast 89%, prostate 99%, colon 65% Only 16 % is diagnosed at an early stage US Congress. Lung Cancer Mortality Reduction Act of 2011

7 Lung Cancer How big is the problem? Stigmatization by society Only cancer blamed on patients but 20% have never smoked 60% are former smokers Economical impact Value of life lost > $433,000,000,000 / year by 2020 Early detection save >70,000 lives / year in the US US Congress. Lung Cancer Mortality Reduction Act of 2011

8 Individual Health Assessment Require evidence Reassurance Exclude dangerous disease Early diagnosis Find dangerous disease early Early treatment Treat this disease while it is not too late Treat it while it is still relatively cheap Aberle D et al. NEJM 2013;369:920

9 Lung Screening Enough evidence?

10 Lung Cancer Screening Trials Early Lung Cancer Action Project Many resected T1 cancers with excellent prognosis 31,567 participants 410 cancers I-ELCAP investigators. N Engl J Med 2006;355:1763

11 National Lung Screening Trial The first large Randomized Controlled Trial

12 National Lung Screening Trial Results NLST Mortality N f/u all-cause cancer others LDCT CXR months Participants: LDCT / CXR 20% reduction of lung-cancer specific mortality ACS, ACCP, ACTS, NCCN now recommend CT screening But Total number of lives save was small (123) Total mortality reduction was 6%

13 National Lung Screening Trial More cancers found Lung cancers More lung cancers were found with LDCT than CXR NLST research team. N Engl J Med 2011;365:395

14 Lung Cancer Screening Multicentric Italian Lung Detection Trial Lung cancer incidence Pastorino U. Eur J Cancer Prevention 2012

15 National Lung Screening Trial Less cancer deaths Death from lung cancer Less lung cancer deaths with LDCT than CXR NLST research team. N Engl J Med 2011;365:395

16 Lung Cancer Screening Multicentric Italian Lung Detection Trial Cancer mortality Pastorino U. Eur J Cancer Prevention 2012

17 Lung Cancer Screening Multicentric Italian Lung Detection Trial All cause mortality Pastorino U. Eur J Cancer Prevention 2012

18 Lung Cancer Screening Denmark: DLCST All-cause mortality Lung cancer mortality Saghir Z et al. Thorax 2012;67:296

19 Lung Cancer Screening What about the European results? Mortality N f/u all-cause cancer others DANTE LDCT Controls 1196 months DLCST LDCT Controls 2058 months MILD LDCT/a LDCT/2a 1186 months Controls

20 Lung Cancer Screening Trials Randomized Controlled Trials LDCT versus CXR NLST USA mm LDCT versus usual care NELSON NL/B mm DLST DK mm 4104 LUSI GER mm >4000 MILD IT mm 4099 ITALUNG IT mm 3206 DANTE IT mm 2472 UKLS UK mm >4000

21 Lung Cancer Screening The European results All published European trial show so far no positive effect (in fact, most show a negative effect of LDCT) But Small numbers: NLST: Short follow-up: NLST: Low pack-years: NLST: participants, cancers participants, cancers months 78 months pack-years 30 pack-years

22 Lung Cancer Screening How many lives will we save? Let s assume NLST results can be reproduced Total mortality reduction 6% over 6.5 years We need to screen 219 subjects to save 1 life 320 subjects to prevent 1 cancer death within this period of time (6.5 years) Costs are substantial, depending on CT and workup Estimations: 30-40,000$ / life year

23 Lung Cancer IHA What to avoid?

24 Individual Health Assessment Customer expectations Many customers have high expectations If I have a cancer, CT will detect it If I am lucky it is not too late If there s a cancer, I want it out If nothing is found, I m safe I know that further tests may be necessary Most, not all Risk of overtreatment Quite, for 1 year I do not worry of complications / side effects of these tests Biggest issue

25 Lung Cancer Screening Nodules can be missed Sensitivity Is never 100% Smaller nodules missed more easily Viewing mode important Experience and fatigue Nodule detection is a boring task 1 year follow-up

26 Individual Health Assessment Expectation management Interval cancers occur very rarely (< 0.1%) Interval cancers are especially fast-growing and deadly One-time IHA Nodules can be missed is dangerous Missed cancers can be detected at follow-up Sensitivity depends on Nodule size Nodule location Radiologist Customers happy IHA and screening detects more early stage cancers Longer screening intervals will detect more indolent cancers Little effect on survival

27 Lung Cancer Screening Denmark: DLCST Saghir Z et al. Thorax 2012;67:296

28 Lung Cancer Screening Denmark: DLCST Saghir Z et al. Thorax 2012;67:296

29 Lung Cancer Screening Screening detects favorable cancer stages Horweg N et al. AJRCCM 2013; 187(8):848

30 Lung Cancer Screening Patient expectations If a cancers is found, it can be treated and I ll survive More cancers detected with chest X-ray screening No survival benefit for chest X-ray screening More cancers detected with chest CT screening 20% cancer-specific survival benefit for CT screening 6% overall survival benefit within 6.5 y follow-up NLST data This means Many patients with lung cancer will still die from lung cancer

31 Nodule Management What is a positive result? NLST Any non-calcified nodule 4 mm NELSON Any solid component of a nodule 500 mm 3 Any solid component of a pleural based nodule 10 mm Any growing nodule with a volume doubling time < 400 d Any non-solid nodule growing > 20% in diameter NLST Research Team.NEJM 2011;365(3):395 van Klaveren R. NEJM 2009;361(23):2221

32 Lung Cancer Screening Program Setup Small nodules may be missed Limited sensitivity of any technique we use One-time screening increases risk of law-suits 1 year follow-up VDT < 400 d

33 Lung Cancer Screening Program Setup Early cancers treated by non-specialized surgeons Small nodules or GGNs cannot be palpated intraoperatively May not be (fully) resected Histology after VATS: Old infarction 3-year follow-up: T2N1 carcinoma 1-year follow-up VDT < 400 d

34 Lung Cancer Screening What to do?

35 Individual Health Assessment Expectation Management Informed consent required Screening will reduce your risk of dying of cancer: 20% lung-cancer mortality reduction in NLST There is still a chance that a lung cancer will kill you Benefit of screening increases with your risk: more damage by unnecessary procedures if your risk is low Most cancer found will be at treatable stage but not all: stage I in 60-80% Because screening may miss nodules, we offer follow-up You have a >20% chance that we find a nodule > 5 mm We advise you if you are high-risk More than 95% of these nodules found are benign Expect follow-up

36 Risk for Maligancy PanCan Trail McWilliams A et al. NEJM 2013; 369:10

37 Lung Cancer Screening Personal risk and screening outcome Higher risk yields more benefits for screening 20% lung-cancer mortality reduction in NLST for age 55-74, 30 pack-years Risk increases with o Age o Smoking history o Male sex o Emphysema o Family history o Asbestos exposure, Various risk calculators available

38 Lung Cancer Screening Trials Early Lung Cancer Action Project I-ELCAP Higher cancer risk at higher age: 0.5 % at years 2.4% at years I-ELCAP investigators. N Engl J Med 2006;355:1763

39 Tammemägi MC et al. NEJM 2013;

40 Nodule Management Only high-risk nodules = positive screening result NLST Any non-calcified nodule 4 mm NELSON Any solid component of a nodule 500 mm 3 Any solid component of a pleural based nodule 10 mm Any growing nodule with a volume doubling time < 400 d Any non-solid nodule growing > 20% in diameter NLST Research Team. NEJM 2011;365(3):395 van Klaveren R. NEJM 2009;361(23):2221

41 Lung Cancer Screening Adequate screening setup Offer a screening program One-time screening is dangerous: missed nodules, risk for law-suits increases One-time screening is costly for the health insurers: many benign lesions sent to regular care Offer a package that includes initial follow-ups Consider yearly screening Consider 25% f/u Train your personnel: at 1 st round administration, radiographers, readers, radiologists Buy adequate software for CAD and volumetry

42 Lung Cancer Screening Adequate screening setup Build a network with pulmonologists and surgeons Screening-detected high-risk lesions are different: o Smaller cancers o Often subsolid lesions o 50% benign Standard workup and treatment may be inadequate: o Bronchoscopic biopsy unsuccesful o Lesions may not be palpable by surgeons o Follow-up may be more adequate than immediate surgery

43 Lung Cancer Screening Small lesions may not be palpable Establish preoperative marking of lesions Platinum coils Spiral localization wire Part solid nodule: 20% growth Histology: adenocarcinoma

44 The Experience with Lung Screening What does it mean for IHA?

45 Individual Health Assessment What we learn from screening Screening works At least in the US, EU results contradictory Effect size depends on disease prevalence Use risk calculators to define eligible individuals Expectation management is crucial Still substantial risk of dying from lung cancer Collateral damage by invasive workup & overdiagnosis

46 Individual Health Assessment What we learn from screening One-time scanning is dangerous Misses cancers Nodule workup causes 20% spill-over into healthcare system Knowledge about collateral damage is increasing Overdiagnosis and overtreatment of indolent tumors Unnecessary workup / treatment of FP disease Collateral risk should limit exams of low-risk individuals

47 Individual Health Assessment What we learn from screening For IHA to be successful, a program is needed Dedicated personnel Optimized techniques Good expectation management Follow-up Experts for treatment of early disease

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