1. Screening for colorectal cancer (CRC) in Europe L. Hol 1, E.J.Kuipers 1,2 1 Department of Gastroenterology and Hepatology and 2 Department of Internal Medicine and Erasmus University Medical Center, Rotterdam. Hungary, October 17 th, 2008

2. Colorectal cancer is the most common malignancy (380,000/year) and the second most common cancer related death (180,000/year) in Europe CRC mortality varies over countries, with Hungary having the highest mortality rates in Europe and Greece having the lowest Nation-wide screening CRC Screening in Europe

3. Screening can reduce CRC mortality due to detection of early carcinomas and removal of pre-malignant lesions 1,2 Nation-wide screening CRC Screening in Europe 1 Winawer, NEJM 1993; 2 Ries LAG 2007;

4. 1.Guaiac-based FOBT (gFOBT) 2.Immunochemical FOBT (FIT) 3.Flexible sigmoidoscopy (FS) 4.Colonoscopy Screening options CRC Screening in Europe

5. Study Age range mortality Nottingham 1 45-75 13% 11 years Funen 2 45-74 11% 17 years Minnesota 3 50-80 21% 18 years Goteborg 4 60-64 16% 15.5 years Guaiac-based FOBT CRC Screening in Europe 1 Mandel JS, NEJM 1993; 2 Kronborg O, Lancet 1996; 3 Hardcastle JD, Lancet 1996; Kewenter, Scan J Gastroenterol 1994

6. FOBT Performance Characteristics Positivity Rate Specificity (Neoplasia) Sensitivity (CRC) Hemoccult II 1 2.598.137.1 Heme Select 2 5.995.268.8 OC-Hemodia 3 6.594.088.9 *In a screening-naïve population; ** Estimated specificity and sensitivity 1 Petrelli N, Surg Oncol 1994; 2 Allison JE, NEJM 1996; 3 Nakama H, Eur J Cancer 2001

7. Sigmoidoscopy screening CountryPopulation Age-group UKFlex 3 UK35426255-64 SCORE 4 Italy236.56855-64 PLCO 5 USA77 46555-74 NORCCAP 6 Norway2078050-64 Two case-control studies demonstrated a 60-80% mortality 1,2 1 Selby, NEJM 1992; Newcomb NEJM 1992 3 UKflex, Lancet 2002; 4 Segnan, JNCI 2002; 5 Weissfeld, JNCI 2005; 6 Gondal Sacn J G 2003

8. Colonoscopy screening CRC Screening in Europe 1 Winawer, NEJM 1993;

9. European health council has recommended CRC screening for average-risk persons aged ≥ 50 years old with any test 6 Today, more than 50% of the target population in the European Union is however offered no screening at all Nation-wide screening programs in European countries vary widely in strategy and quality guidelines are lacking, hereby hampering efficacy Nation-wide screening 6 Commission of the European Communities Brussels, 2003 CRC Screening in Europe

10. Set up an European action plan. Provide European health ministers with an European guideline for CRC screening. Include practical assistance in the detection and management of high- risk groups. Include a demand for provision of all target groups with adequate information. Implement any national screening programme using call/recall system through a central agency. Implement any national screening programme based on quality- assured and quality-controlled infrastructure. Advise the member states to facilitate the provision of appropriate training to personnel involved in screening, processing of results and subsequent treatment. Establish and fund designated research programmes for the development and evaluation of programmes for CRC screening. Brussel declaration 7 International union against cancer. Brussel guidelines 2007 CRC Screening in Europe

11. Set up an European action plan. Provide European health ministers with a European guideline for CRC screening. Include practical assistance in the detection and management of high- risk groups. Include a demand for provision of all target groups with adequate information. Implement any national screening programme using call/recall system through a central agency. Implement any national screening programme based on quality- assured and quality-controlled infrastructure. Advise the member states to facilitate the provision of appropriate training to personnel involved in screening, processing of results and subsequent treatment. Establish and fund designated research programmes for the development and evaluation of programmes for CRC screening. Brussel declaration 7 International union against cancer. Brussel guidelines 2007 CRC Screening in Europe

12. Nation-wide screening (call/recall) CRC Screening in Europe

13. Opportunistic programs CRC Screening in Europe

14. Regional programs CRC Screening in Europe

15. Pilot programs CRC Screening in Europe

16. CountryTestIntervalAgeParticipation EnglandgFOBTBiennial60-6950-70% ScotlandgFOBTBiennial50-74 Nation-wide program (call/recall) CRC Screening in Europe

17. CountryTestIntervalAgeParticipation AustriagFOBT Sigmoidoscopy Colonoscopy Annual Biennial 5-yearly 10-yearly 50-55 ≥ 55 CzechgFOBT / FITBiennial≥ 50<50% GermanygFOBT Colonoscopy Annual Biennial 10-yearly 50-55 ≥ 55 <20% PolandColonoscopy10-yearly≥ 50<10% SlovakiaColonoscopy10-yearly≥ 50<30% Nation-wide program (opportunistic) CRC Screening in Europe

18. CountryTestIntervalAgeCoverage FinlandgFOBTBiennial60-69 FrancegFOBTBiennial50-7430-51% ItalyFIT Sigmoidoscopy Both Biennial 5-yearly ≥ 50 15-70% Regional programs CRC Screening in Europe

19. Pilot program in the Netherlands Introduction (I) 2001 Dutch Health council: CRC screening should be considered. 2006 Start pilot studies 2008 Dutch Health council: Nation-wide CRC screening program most likely based on FIT will be introduced in the Netherlands in 2010. Studies on endoscopic screening are needed

20. Primary aim To determine the attendance rate of guaiac based faecal occult blood test (gFOBT), immunochemical FOBT (FIT) and flexible sigmoidoscopy (FS) for CRC screening. Secondary objective To determine the detection rate of advanced neoplasia and colorectal carcinoma of the three screening tests Aim Introduction (II)

21. Time frameNovember 2006 – November 2007 CORERO-trial Methods (I) DesignPopulation based Randomised trial RandomisationPrior to invitation Per household InclusionAverage risk men/women Screening naïeve Aged 50-75 years old

22. Trial profile Results (I) gFOB T 5004 were invited 206 were excluded 4748 were eligible 2374 (50%) attended FIT 5007 were invited 4843 were eligible 2979 (62%) attended 164 were excluded FS 5000 were invited 1522 (32%) attended 4700 were eligible 300 were excluded

23. % Attendance: men / women P=0.01 Results (II) P<0.001 Univariate analysis

24. Findings Results (III) * Findings during sigmoidoscopy and colonoscopy; Advanced adenoma: adenoma ≥ 10 mm, villous component (≥ 25% villous) or high-grade dysplasia; serrated adenoma; three or more adenomas.

25. Advanced neoplasia per 100 invited Results (V) Advanced neoplasia / 100 invited 3.0 2.5 2.0 1.5 1.0 0.5 0.0 P<0.001

26. Conclusie  FIT screening should be preferred over guaiac- based FOBT screening  Sigmoidoscopy screening seems to be most effective, but RCTs have to be awaited to determine the CRC incidence and mortality reduction due to FS screening Summary CORERO-trial Conclusion (II)

27. Main issues of CRC screening in Europe CRC Screening in Europe Quality assurance (European guidelines) Uptake / coverage Endoscopy resources

28. Quality assurance Four out of ten nation-wide programs do not have national guidelines for CRC screening European guidelines are currently being made (IARC) - Organisation - Evaluation and interpretation of screening outcomes - Quality assurance for endoscopy - Professional requirements and training - Quality assurance for pathology - Management of screen detected lesions - Surveillance CRC Screening in Europe

29. Uptake / coverage Uptake of CRC screening is generally low High attendance is a prerequisite for an effective colorectal cancer (CRC) screening program A recall system is preferable over opportunistic screening 7 7 International union against cancer. Brussel guidelines 2007 CRC Screening in Europe

30. Public awareness 8 Keighley M, Eur J Cancer Prev 2004 CRC Screening in Europe Willingness to be screened depends on awareness of colorectal cancer and CRC screening A survey among people in the target population in 21 European countries showed 8 51% had knowledge of CRC screening 75% were 'very', or 'quite interested’, in taking up faecal occult blood (FOB) screening if offered free Lack of awareness of risk (31%) was a main barrier to CRC screening

31. Endoscopy resources No solid data on endoscopy resources in Europe Endoscopy capacity varies per region 9,10,11 Required resources depend on Target population Screening test (positivity rate) Screening interval Attendance rate Guidelines for surveillance CRC Screening in Europe 9 Ladabaum U, Gatroenterol 2005, 10 Butterly L, Am J Prev Med 2007, 11 Seeff LC, Gastroenterol 2004

32. Positivity rate Cut-off% Positive Grazzini, 2004100ng5.8 Segnan, 2005100ng4.6 Segnan, 2007100ng4.7 Guittet, 200775ng2.4 Van Rossum, 2008100ng5.5 Hol, 2008100ng4.8 CRC Screening in Europe

33. Colonoscopy resources FIT (2yr) gFOBT (2yr) Sigmo (5yr) Colono (10yr) 2005 2010 2015 2020 2025 Year CRC Screening in Europe

34. Conclusie 1. Several initiatives for CRC screening in Europe 2. Only one country with a nation-wide screening program (call / recall system) 3. European guidelines will be available in 2009 4. European countries should collaborate for further improvement of CRC screening quality Conclusions CRC Screening in Europe

35. The team Gastroenterology Lab Angela Heijens Jan Francke Martine Ouwendijk Nicolle Nagtzaam Endoscopy unit Jelle Haringsma Maurice Laban CORERO-trial Steering Committee Ernst Kuipers Dik Habbema Monique van Leerdam Marjolein van Ballegooijen Hanneke van Vuuren Sandra van der Togt Jaqueline Reijerink Lieke Hol Advisory board Mrs. I. Joung Mrs. A. Cats J.W. Coebergh