Pathology in the UK Bowel Cancer Screening Programmes

1. Pathology in the UK Bowel Cancer Screening Programmes Frank Carey (Dundee)

2. Screening for Large Bowel Cancer • Faecal occult blood (FOB) • Guaiac • Immunological • Sigmoidoscopy • Colonoscopy • CT Colography

3. FOB Screening for colorectal Cancer • The research • The pilot • The programmes • Pathology

4. The Research • Population screening with FOB + colonoscopy reduces disease-specific mortality from colorectal cancer • Mandel et al N Engl J Med 1993 • Kronborg et al Lancet 1996 • Hardcastle et al Lancet 1996

5. Meta-Analysis of FOBT Trials • Overall relative risk of death • 0.84 (CI 0.77 - 0.93) • 16% reduction in deaths • Adjusted for uptake • 0.77 (CI 0.57 - 0.89) • 23% reduction in deaths (Towler et al 1998)

6. Effect of Screening on Colorectal Cancer Incidence Control group Screened groups

7. UK Pilots (2000 onwards) • Aim: to test feasibility of screening in “real life” NHS • Coventry and Warwickshire • Fife, Grampian and Tayside (each with approx. 1m pop.)

8. Operation of Pilots • Central call/recall, administration, helpline • Postal delivery of FOB kits • Analysis in newly constructed labs (run by Biochemistry) • Minimum primary care involvement • Screening Group (lead clinician, surgery, pathology, biochemistry, nursing, public health, radiology)

9. Screening Pilot Start date: 29 March 2000 • Postal delivery of test kit from Centre • One reminder test kit • Dietary restriction for weak positive • Nurse interview • Colonoscopy

13. UK First Round Screening Algorithm Guaiac FOBT WP [1-4 spots positive] P [5-6 spots positive] Retest WPN WPP [any spot P] Retest Investigation WPNP [any spot P] WPNN Repeat tests had dietary restriction

14. Key Performance Indicators (KPIs) • Uptake • overall • by deprivation category • response rate to first invitation • response rate to reminders • Time to colonoscopy • Proportion of +ves undergoing colonoscopy • Colonoscopy completion rate • Colonoscopy complication rate • admissions • perforations • bleeding • deaths • Positivity rate • Cancer Detection Rate • Stage at diagnosis (incl. polyp cancers) • Adenoma detection rate • overall • high risk • PPV • for cancer • for adenoma • for high risk adenoma • for any neoplasia

15. KPI 1(Uptake)

16. Age and Sex Uptake, % Age range

17. Deprivation Category Uptake, % SIMD

18. KPI 1(Uptake)

19. KPI 2(Time to colonoscopy)

20. KPI 3(Proportion of FOBT positive individuals undergoing colonoscopy) (provisional)

21. KPI 4(Colonoscopy completionrate) (provisional)

22. KPI 5 (Colonoscopy complication rates)

23. KPI 6(FOB positivity) (provisional)

24. KPI 7(Cancer detection rate /1000 screened) (provisional)

25. KPI 8(Stage at diagnosis)

26. Stage Distribution of Symptomatic Colorectal Cancer A 8% D 25% B 33% C 34%

27. Stage Distribution of Screen -Detected Cancers D 1% True A 26% C 26% 48% B 25% Polyp Cancers 22%

28. Meaning of FOBT + • Initial positivity 2%. Of these; • 40% have neoplasia (30% adenoma 10% cancer) • 10% have something else (eg inflammatory bowel disease)

29. Colonoscopy Activity at Ninewells Hospital (by quarter) Start of screening

30. Workload change in Ninewells pathology *Overall effect on colorectal specimen number is not large

31. First NHS screening colonoscopy • Asymptomatic solitary sigmoid polyp (11mm) • Complete excision of moderately differentiated adenocarcinoma (no lymphatic/vascular invasion)

32. All Cancers – Screened Health Boards P<0.01 54% 48% 42% 37% * Screening will save 150 lives per year in Scotland

33. Cancers in a screened population • Screen detected • Interval cancers (about half of all cancers in screened population in Nottingham) • After negative FOB • After positive FOB/negative colonoscopy • Cancers in those refusing FOB screening

34. Polyps bleed…….. • About 2900 polyps were removed in the Scottish Pilot 1st round • Vast majority hyperplastic polyps or adenomas

35. Adenomas in Screening • Adenomas much more common than cancers • Adenomas are the precursors of most cancers • Adenomas (even when removed) are a marker of cancer risk • The programme is almost as much about adenomas as cancer

36. KPI 9(Adenoma detection rate/1000 screened)

37. KPI 10(PPV)

38. Interval Cancers(All cancers diagnosed in the population who responded to the 1st round screening invitation within 2 years of their FOBT result)

39. Adenoma Follow-up Scheme Low risk 1 or 2 small adenomas <10mm Intermediate risk 3 or 4 adenomas or, at least one >10mm High risk (1) 5 or more adenomas or, At least three >10mm High risk (2) Large sessile adenoma removed piecemeal A B C D Colonoscopy at 3 years Colonoscopy at 1 year Check eradication at three months ?re-treat D ? needs surgery Surveillance by FOBt * (or exceptionally colonoscopy at 5 years) • Findings at follow up: • No adenomas B • No adenomas x 2 cease follow up • Intermediate or high risk B or C • Findings at follow up: • No adenomas B • Intermediate or low risk B • High risk C • Inspect at 1 year • No adenoma B Notes: Low risk adenomas: Patients in whom one or two small tubular adenomas are removed are at no significant additional risk of developing colonic cancer, and may have a reduced risk of developing rectal cancer, when compared with the unexamined population. Surveillance by FOB testing within the screening programme is recommended. Polyp cancers- Histology should be reviewed and further management discussed at an appropriate Multi-Disciplinary Team meeting. If surgical resection is not indicated then the patient should be followed in the high risk category

40. Pathological measurement of polyp size

41. Bowel Screening Programmes • England – initially 60-69 years (pilot was 50-69) • Scotland – 50-74 years* • Wales – in planning stages • N. Ireland – no immediate plans *Peak incidence is approximately 72 years

42. Programme Organisation • England: • Screening hubs provide call/recall, FOB laboratory, facilitate polyp surveillance • Screening centres provide nurse clinics, colonoscopy, pathology, cancer treatment • Scotland: • Central FOB laboratory, call/recall centre in Dundee. All other activity devolved to local NHS Boards

43. Funding • New funding available in England (including allocation for pathology) • Funding contingent on gathering of agreed datasets • No additional funding in Scotland

44. Pathology • Make a diagnosis • Plan treatment and follow up • Collect accurate data • Audit of service development • Facilitate high quality research

46. Applied research • Effect of programme on mortality • Diagnostic accuracy in early cancers • Prognosis in screen detected early stage cancer • Polyp cancers • Interval cancers • Cancers in those declining screening • Follow-up of adenomas • Does adenoma removal reduce the incidence of cancer Resource includes data andtissue (for molecular and immunohistochemical study)

47. UK Bowel Screening Programs • Probably the best database on adenoma and early colorectal cancer in the world • A major opportunity

48. Role of FIT?(Faecal ImmunochemicalTesting)

49. FOBtTechnology • Traditional guaiac tests • Hemoccult, Hema-screen, ColoScreen • Sensitive guaiactests • Hemoccult Sensa, ColoScreen ES • Immunochemical tests • InstantView, immunoCARE, Hemosure,Inform, Confirm, Hemascreen Specific