1. Bowel Screening in Scotland – Current Challenges and Possible Solutions Prof. Bob Steele Ninewells Hospital, University of Dundee

2. Proving Screening Works Population-based randomised trials in which the whole group offered screening (including refusers and interval cancers) is compared with the control group

4. Disease-Specific Mortality in gFOBT Randomised Trials (Relative Risks) Minnesota –Annual0.67 (CI 0.51-0.83) –Biennial0.79 (CI 0.62 - 0.97) Nottingham –Biennial0.85 (CI 0.74 - 0.98) Funen –Biennial0.82 (CI 0.68 - 0.99) Göteborg –Biennial0.84 (CI 0.71-0.99)

5. National UK Colorectal Cancer Screening Pilot Aim: to test the feasibility of introducing gFOBT screeing into the NHS

7. Single Centre Investigation and treatment devolved to health boards (n=14) Age range 50 - 74 Organisation of the bowel cancer screening programme - Scotland

9. Rate ratio of Colorectal Cancer invited vs controls Overall 0.90 (0.830 – 0.989) Relative reduction in CRC mortality 10% Participants only 0.73 (0.653 – 0.824) Relative reduction in CRC mortality 27%

10. Positive Predictive Value of Screening Colonoscopy Carcinoma14.6% Adenoma35.9% No Neoplasia 49.5%

11. Uptake - Gender and Deprivation % SIMD

12. Round 1Round 2Round 3 Screen -detected351 (56.6%) 208 (46.5%) 139 (35.7%) True interval193 (31.2%) 213 (47.7%) 229 (58.9%) Missed2 (0.3%) 4 (0.9%) 2 (0.5%) Miscellaneous66 (10.7%) 22 (4.9%) 19 (4.9%) Not on Socrates6 (1%) 00 Cancers Diagnosed in the Screened Population

13. Gender distribution - all rounds %

14. Site distribution - all rounds %

15. Issues to address Interval Cancers Gender inequality Rectal and right-sided cancers Uptake

16. “Blood in stool” tests Flexible Sigmoidoscopy Colonoscopy

17. No RCT results Case control studies only But – highly sensitive and 100% specific

18. If an insensitive test with imperfect specificity reduces mortality…..

19. TestAccuracyAcceptabilityRisk FOBT++++- Flex-sig++ + Colonosc++++ £££££ £

20. ICRF/MRC Study (Oct 1996 – March 1999) Single flexible sigmoidoscopy with removal of adenomas –55-64 years High risk colonoscopy –adenoma > 1cm –3+ adenomas –tubulovillous or villous histology –20+ hyperplastic polyps above distal rectum –cancer

21. ICRF/MRC Study Total no: 354262 Interested : 194726 (55%) Randomised: 170432 Control: 113178 Invited for screening: 57254 Attended: 40674 (71%)

22. Mortality from CRC

23. Incidence of CRC

24. Incidence of L-sided CRC

25. Incidence of R-sided CRC

26. Potential Advantages of FS Disease prevention –Enhanced detection of left-sided adenomas Detection of rectal cancer Unlikely to be a gender difference

27. Potential Problems with FS Uptake –Unlikely to be >30% –Possibility of exaggerated deprivation gradient Effect on right-sided cancers

28. Alternative Strategy Increasing sensitivity of FOBT?

29. gFOBT vs FIT gFOBT –Based on Guaiac reaction –Not specific for haemoglobin –Messy to do FIT –Immunological –Specific for human haemoglobin –Easy to do –QUANTITATIVE

30. Quanitative FIT and Disease

31. n=20358 n=17783 “FIT 400”

32. n=20358 n=17783 “FIT 50”

33. Sensitivity Specificity

34. FIT 50 10% positivity rate 90% sensitive for cancer 40% sensitive for adenoma Lower detection limit may be more sensitive But…

35. Question Sigmoidoscopy for all FIT 50 and colonoscopy for ~ 10% or ?

36. Potential Pros Sigmoidoscopy –Detection of left-sided adenomas and protection from left sided cancer –Detection of rectal cancer FIT 50 –Uptake –Detection of right-sided cancer