PSA & CRC screening Siffer og skjebne. Beslutninger under usikkerhet

Transkript

1 PSA & CRC screening Siffer og skjebne. Beslutninger under usikkerhet John Brodersen, MD, GP, PhD, lektor Forskningsenheden og Afdeling for Almen Medicin IFSV, Københavns Universitet

2 PSA & CRC screening Absolutte og relative tal PSA-screening CRC-screening John Brodersen, 2

3 Absolutte & relative tal 2 ud af dør, reduceres til 1 ud af 1.000: 50% relativ risikoreduktion 0,1% absolutte risikoreduktion Number Needed to Treat (NNT) er ud af 100 dør, reduceres til 1 ud af 100: 50% relativ risikoreduktion 1% absolutte risikoreduktion Number Needed to Treat (NNT) er ud af 10 dør, reduceres til 1 ud 10 dør: 50% relativ risikoreduktion 10% absolutte risikoreduktion Number Needed to Treat (NNT) er 10 John Brodersen, john.brodersen@sund.ku.dk 3

4 Optimalt scenarium Esserman L., Shieh Y., & Thompson I. Rethinking Screening for Breast Cancer and Prostate Cancer. JAMA: 302 (15): , John Brodersen, 4

5 Værste scenarium Esserman L., Shieh Y., & Thompson I. Rethinking Screening for Breast Cancer and Prostate Cancer. JAMA: 302 (15): , John Brodersen, 5

6 Intermediært scenarium Esserman L., Shieh Y., & Thompson I. Rethinking Screening for Breast Cancer and Prostate Cancer. JAMA: 302 (15): , John Brodersen, 6

7 Stadieskifte Esserman L., Shieh Y., & Thompson I. Rethinking Screening for Breast Cancer and Prostate Cancer. JAMA: 302 (15): , John Brodersen, 7

8 PSA-screening Esserman L., Shieh Y., & Thompson I. Rethinking Screening for Breast Cancer and Prostate Cancer. JAMA: 302 (15): , John Brodersen, 8

9 PSA-test and Pca in DK Antal prøver Antal incidente cancer prostata Almen praksis er rekvirent Speciallæge/sygehus er rekvirent Incidente cancer prostatae T. O. Mukai, F. Bro, K. V. Pedersen, P. Vedsted. Brug af undersøgelse for prostataspecifikt antigen. Ugeskr.Laeger 172 (9): , John Brodersen, john.brodersen@sund.ku.dk 9

10 PSA-screening Ilic et al. Screening for prostate cancer. Cochrane Database, John Brodersen, 10

11 PSA-screening 1410 ( ) men (50 69y) invited every 4 th year, follow-up 9 years (participation 82%): 1 prevented death of prostate cancer Incidence increased: 4.8%-8.2% (70%) 47 overdiagnosed Schroder Z.H. et al. Screening and Prostate-Cancer Mortality in a Randomized European Study. N Engl J Med., John Brodersen, john.brodersen@sund.ku.dk 11

12 PSA-screening Hugosson J et al. Mortality results from the Göteborg randomised population-based prostate-cancer screening trial. Published online July 1, 2010 John Brodersen, john.brodersen@sund.ku.dk 12

13 PSA-screening Hugosson J et al. Mortality results from the Göteborg randomised population-based prostate-cancer screening trial. Published online July 1, 2010 John Brodersen, john.brodersen@sund.ku.dk 13

14 PSA-screening Schroder Z.H. et al. Prostate-Cancer Mortality at 11 Years of Follow-up. N Engl J Med., John Brodersen, john.brodersen@sund.ku.dk 14

15 PSA-screening 1055 ( ) men (50 69y) invited every 4 th year, follow-up 11 years (participation 82%): 1 prevented death of prostate cancer Incidence increased: 6.0%-9.6% (60%) 37 overdiagnosed Schroder Z.H. et al. Prostate-Cancer Mortality at 11 Years of Follow-up. N Engl J Med., John Brodersen, john.brodersen@sund.ku.dk 15

16 PSA-test and Pca in DK PSA test Total antal PSA test fordelt pr. år Year Year Normalt resultat - Almen er rekvirent Forhøjet resultat - Almen er rekvirent Normalt resultat - Specialist er rekvirent Forhøjet resultat - Specialist er rekvirent Flemming Bro, Professor i almen medicin og leder af Forskningsenheden for Almen praksis i Århus John Brodersen, john.brodersen@sund.ku.dk 16

17 Konklusion PSA screening Usikkert om PSA-screening kan nedsætte dødeligheden af prostatakræft PSA-screening medfører skade, især Overdiagnostik Overbehandling John Brodersen, 17

18 FOBT-screening Cochrane 15% relativ risikoreduktion Hewitson P et al. Screening for colorectal cancer using the faecal occult blood test, Hemoccult. Cochrane.Database.Syst.Rev. (1):CD001216, John Brodersen, john.brodersen@sund.ku.dk 18

19 Cochrane review inviteres (60% deltagelse), alder 50 74, hvert andet år i 10 år 5 runder: 7,35 undgået dødsfal af tarmkræft 72 sandt positive resultater 54 falsk negative resultater >900 falsk positive resultater Overdiagnose af polypper (ppv = 0,4 0,7%) 2,92 komplikationer, 0,08 0,25 dødsfald Hewitson P et al. Screening for colorectal cancer using the faecal occult blood test, Hemoccult. Cochrane.Database.Syst.Rev. (1):CD001216, John Brodersen, john.brodersen@sund.ku.dk 19

20 Undgåede CRC-dødsfald i DK nye tilfælde af CRC om året Livstidsrisikoen er ca. 5% Ca i aldersgruppen år 5 års overlevelsen er ca. 50% vil dø af tarmkræft i aldersgruppen år 15% af = 150 undgåede dødsfald John Brodersen, john.brodersen@sund.ku.dk 20

21 CRC-screening i Norden Percentage Denmark Finland Iceland Norway Sweden Age groups Sigurdsson J.A., Getz L., Sjönell G., Vainiomäki P., Brodersen J. Marginal public health gain of screening for colorectal cancer. Journal of Evaluation in Clinical Practice. Accepted for publication 12 March John Brodersen, john.brodersen@sund.ku.dk 21

22 CRC-screening i Norge Sigurdsson J.A., Getz L., Sjönell G., Vainiomäki P., Brodersen J. Marginal public health gain of screening for colorectal cancer. Journal of Evaluation in Clinical Practice. Accepted for publication 12 March John Brodersen, john.brodersen@sund.ku.dk 22

23 CRC-screening i Danmark Sigurdsson J.A., Getz L., Sjönell G., Vainiomäki P., Brodersen J. Marginal public health gain of screening for colorectal cancer. Journal of Evaluation in Clinical Practice. Accepted for publication 12 March John Brodersen, john.brodersen@sund.ku.dk 23

24 CRC-screening i Sverige Sigurdsson J.A., Getz L., Sjönell G., Vainiomäki P., Brodersen J. Marginal public health gain of screening for colorectal cancer. Journal of Evaluation in Clinical Practice. Accepted for publication 12 March John Brodersen, john.brodersen@sund.ku.dk 24

25 CRC-screening i Finland Sigurdsson J.A., Getz L., Sjönell G., Vainiomäki P., Brodersen J. Marginal public health gain of screening for colorectal cancer. Journal of Evaluation in Clinical Practice. Accepted for publication 12 March John Brodersen, john.brodersen@sund.ku.dk 25

26 CRC-screening i Island Sigurdsson J.A., Getz L., Sjönell G., Vainiomäki P., Brodersen J. Marginal public health gain of screening for colorectal cancer. Journal of Evaluation in Clinical Practice. Accepted for publication 12 March John Brodersen, john.brodersen@sund.ku.dk 26

27 Mulige bias? En undersøgelse Critical appraisal of the literature Fire RCT er fra Cochrane reviewet Kontakt til alle første forfattere Kontakt til Cochrane forfattere John Brodersen, 27

28 Mulige bias? Hemoccult-II Koloskopi Operation Speciallæge Universitetshospital Logistik og tid Symptomer Rectoskopi/ Røntgen af colon Operation Læge Alle sygehuse Logistik og tid John Brodersen, 28

29 Place of surgery OR på 1,22 (CC), 1,38 (RC) og 1,17 (CRC) L. H. Iversen, H. Harling, S. Laurberg, and P. Wille-Jorgensen. Influence of caseload and surgical speciality on outcome following surgery for colorectal cancer: a review of evidence. Part 2: long-term outcome. Colorectal Dis. 9 (1):38-46, John Brodersen, john.brodersen@sund.ku.dk 29

30 Delay Danmarks befolkning 1998: 68 dage 2000: 55 dage 2010: 27 dage Fyn-undersøgelsen : 24 dage John Brodersen, 30

31 Delay ved rectalcancer Risiko for avanceret rectalcancer: < 60 dage = 26,5% dage = 49,5% > 150 dage = 54,9% Korsgaard M, Pedersen L, Sorensen HT, Laurberg S. Delay of treatment is associated with advanced stage of rectal cancer but not of colon cancer. Cancer Detect Prev 2006;30(4): John Brodersen, john.brodersen@sund.ku.dk 31

32 Mulige bias? En undersøgelse Type of bias Funen Goteborg Nottingham Minnesota Type of diagnostic method A C C C Place of surgery A C C A Diagnostic delay A C C C Exclusion of deaths due to complications B A C C Selection bias B B A A Change of FOBT during the study B A B A A: Evidence of the presence of bias, B: Evidence of the absence of bias, C: Absence of evidence of bias

33 Mulige bias? En undersøgelse Conclusion Of the six biases found, five favour screening. Therefore, the 16% RRR in CRC-mortality found in the meta-analysis in the updated Cochrane review is overestimated. Riboe D., Dogan T.S., Brodersen J. Potential Biases in Colorectal Cancer Screening using Faecal Occult Blood Test. Journal of Evaluation in Clinical Practice. Accepted for publication 29 November John Brodersen, 33

34 Konklusion CRC screening Usikkert om FOBT-screening kan nedsætte dødeligheden af ende- og tyktarmskræft og hvis den kan, kendes effektstørrelsen ikke Den forebyggende effekt på for tidlige død blandt årige er 0-1% FOBT-screening medfører skade John Brodersen, 34