Lung Cancer Screening: A review of the recommendations Friday, November 11th, 2016 from 11:45 to 12:15. Dr. Tunji Fatoye Dr.

Transcription

1 Lung Cancer Screening: A review of the recommendations Friday, November 11th, 2016 from 11:45 to 12:15 Dr. Tunji Fatoye Dr. Alan Kaplan

2 Conflict of Interest Disclosure: Speaker Name: Alan Kaplan FINANCIAL DISCLOSURE Grants/Research Support: Boehringer Ingelheim Speaker Honoraria: Astra Zeneca, BI, Pfizer, Purdue, Takeda, Novartis, Merck Frosst, Griffols, Sanofi Consulting Fees: Takeda, Novartis, Pfizer, Astra Zeneca Other: Public Health Agency of Canada Section of Allergy and Respiratory Therapeutics PHAC, Section on Respiratory Surveillance

3 Conflict of Interest Disclosure Speaker Name - Tunji Fatoye None

4 Disclosure of Commercial Support none Potential for conflict(s) of interest: nil Mitigating Potential Bias None to mitigate other than smoking is against tobacco companies!!

5 Lung Cancer screening: Learning Objectives Epidemiology of lung cancer Does screening work and? How should it be done? Canadian Recommendations?

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 can potentially save >70,000 lives / year in the US US Congress. Lung Cancer Mortality Reduction Act of 2011

8 Canadian Statistics burden of cancer

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10 Estimated Canadian lung cancer statistics (2016) Category Males Females New cases 14,400 14,000 Incidence rate (for every 100,000 people)* Deaths 10,900 9,800 Death rate (for every 100,000 people)* 5-year net survival (estimates for ) % 20%

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12 Bronchogenic Cancer Screening? High mortality ( incidence) Good survival in stage I Screening Survival benefit? Smoking = main risk factor Lots of cardiovascular co-morbidity No advantage for CXR screening found High cost Pro Contra

13 Bronchogenic Cancer CT Screening? First attempts in Japan in1990 Spectacular results from ELCAP in 1995 Similar results from Japan and Münster RCTs start after 2000: NLST (US) und NELSON (NL/B) were largest National trials in other countries

14 Lung Cancer Screening Observational Trials

15 Lung Cancer Screening Trials Early Lung Cancer Action Project I-ELCAP 405 cancers / 31,567 baseline scans (1.3%) 74 cancers / 27,456 follow-up scans (0.27%) 5 interval cancers 412 / 484 (85%) stage I Mainly adenocarcinomas I-ELCAP investigators. N Engl J Med 2006;355:1763

16 Lung Cancer Screening Trials Early Lung Cancer Action Project 31,567 participants 410 cancers I-ELCAP investigators. N Engl J Med 2006;355:1763

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

18 I-ELCAP investigators. N Engl J Med 2006;355:1763

19 Lung Cancer Screening Randomized Controlled Trials: NLST

20 National Lung Screening Trial The Largest Randomized Controlled Trial

21 National Lung Screening Trial The Largest Randomized Controlled Trial

22 National Lung Screening Trial Screening is now recommended

23 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

24 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

25 National Lung Screening Trial LDCT = 1060 lung cancers * CXR = 941 cancers * LDCT arm CXR Arm Stage IA Stage IB-IIB Stage III-IV NLST research team. N Engl J Med 2011;365:395

26 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 But Total number of lives saved was small (123/26722 = 0.4%) Total mortality reduction was 6%

27 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

28 However there is harm.

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32 Lung Cancer Screening The European Multicenter Trials

33 Lung Cancer Screening Trials Randomized Controlled trials In Europe LDCT versus usual care NELSON NL/B , 1, 2, 4, 6y Total DLST DK , 1, 2, 3, 4, 5y 4104 LUSI GER , 1, 2, 3, 4, 5y >4000 MILD IT NA 0, 1, 2, 3, 4y 4099 ITALUNG IT NA 0, 1, 2, 3, 4y 3206 DANTE IT NA 0, 1, 2, 3, 4, 5y 2472 UKLS UK y >4000 LDCT versus CXR NLST USA , 1, 2, 3y 53454

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

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

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

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

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

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

40 Infante M. AJRCCM 2015 Lung Cancer Screening DANTE

41 Infante M. AJRCCM 2015 Lung Cancer Screening DANTE

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

43 Lung Cancer Screening Workup

44 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

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46 Lung Cancer Screening Risk Prediction

47 PANCAN Risk Model for Maligancy PanCan Trial McWilliams A et al. NEJM 2013; 369:10

48 Lung Cancer Screening NELSON: Location of Cancers Horweg N et al. AJRCCM 2013; 187(8):848

49 From Lung Cancer to Heart Screening? Coronary Heart Disease Survival rates Any calcification increases risk Agatston scores fit in same risk category Agatston scores > 400 increase risk by factor 12! Takx RAP et al. JCCT 2015;9.50

50 Lung Screening Trials Summary

51 Lung Cancer Screening Trails Summary Reduction in lung cancer-specific mortality: NLST No reduction in lung cancer-specific mortality: DANTE, ITALUNG, MILD, DLCST (Italy, Denmark) Results pending: NELSON, UKLS, LUSI (Netherlands/Belgium, Germany, UK) Potential explanation Lower risk: 20 vs. 30 pack-years, > 50 vs. > 55years Shorter follow-up / smaller numbers Larger number of interval cancers Differences in workup / treatment?

52 Lung Cancer Screening What now? What happens if screening is widely introduced? We know it works under exactly the conditions of NLST: Technical and management quality no major issue Radiologist s performance variable Workup and treatment worldclass centers Will it still work in community setting? Will it work in Europe?

53 Lung Cancer Screening What now? What happens if screening is widely introduced? We know it works under exactly the conditions of NLST: Technical and management quality no major issue Radiologist s performance variable Workup and treatment worldclass centers Will it still work in community setting? Will it work in Canada? Very low complication rates = 1/3 of US average

54 Canadian Guidelines

55 Canadian Guidelines Key points Because of the potential for screening-related harms, low-dose CT and subsequent management should be done in health care settings with expertise in early diagnosis and treatment of lung cancer. Over 6.5 years, 322 people would need to be screened with low-dose CT to prevent one death from lung cancer.

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58 What about incidental nodules?

59 Ontario Current studies undergoing: eg Brampton Civic Three Pilot sites funded by Cancer Care Ontario Bottom line: this is NOT yet state of the art, but you need to know about this, for when patients ask you. Certain rules: CXR does not work NLST criteria: yo, smokers or quit < 15 y, 30 pack years ONLY currently eligible

60 What about the USA? In USA, it has been rolled out...but: In a community hospital in northern Virginia during the first year after publication of the guidelines. Nearly one-quarter of patients who received screening CT scans did not meet USPSTF criteria. In patients who did meet screening criteria, 65% of scans detected lung nodules, and half of the remaining 35% had another possibly significant finding In a University of Minnesota affiliated health system found that counseling and shared decision making were documented in less than half of outpatient visits for those who underwent screening scans. [2] About 70% of patients had a clinically significant finding on their first scan, although only 17% required follow up sooner than 1 year. In contrast, only 27% of participants in the National Lung Screening Trial, had abnormalities on their first CT scan 1. Ledford CJ, Gawrys BL, Wall JL, et al. Translating new lung cancer screening guidelines into practice: the experience of one community hospital. J Am Board Fam Med. 2016;29: Begnaud A, Hall T, Allen T. Lung ca (vs in NLST only 27% haf ncer screening with low-dose CT: implementation amid changing public policy at one health care system ASCO Educational Book:e468.

61 What does the AAFP say? The National Lung Screening Trial results had not been reproduced in a community setting. The harms of repeat scans, bronchoscopy, or thoracotomy for positive findings might conceivably outweigh the potential benefits if patients who aren't at high risk for lung cancer are screened inappropriately, or too many suspicious findings turn out to be harmless "incidentalomas The jury is still out on whether the guidelines will end up doing more good than harm.

62 My Take: In a patient meeting NLST criteria, feel free to send them to a lung screening program Do not screen yourselves and This might not even work!!! (and will cost a LOT of money...)