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 InvestigationWPNP [any spot P] WPNN Repeat tests had dietary restriction

14. Key Performance Indicators (KPIs) 1.Uptake –overall –by deprivation category –response rate to first invitation –response rate to reminders 2.Time to colonoscopy 3.Proportion of +ves undergoing colonoscopy 4.Colonoscopy completion rate 5.Colonoscopy complication rate –admissions –perforations –bleeding –deaths 6.Positivity rate 7.Cancer Detection Rate 8.Stage at diagnosis (incl. polyp cancers) 9.Adenoma detection rate –overall –high risk 10.PPV –for cancer –for adenoma –for high risk adenoma –for any neoplasia

15. KPI 1 (Uptake) 1 st round2 nd round3 rd round (provisional) Overall 1 st invite 55% 44% 53% 51% 50%

16. Age and Sex Uptake, % Age range

17. Deprivation Category Uptake, % SIMD

18. KPI 1 (Uptake) 2 nd round3 rd round (provisional) Non-responders in previous round Responders in previous round 14% 85% 13% 87%

19. KPI 2 (Time to colonoscopy) 1 st round2 nd round3 rd round (provisional) 2 weeks 4 weeks 6 weeks 20% 40% 65% 26% 61% 76% 50% 84% 97%

20. KPI 3 (Proportion of FOBT positive individuals undergoing colonoscopy) 1 st round2 nd round 3 rd round 85.5% 85.9% 87.3% (provisional)

21. KPI 4 (Colonoscopy completion rate) 1 st round2 nd round 3 rd round 88.0% 90.9% 94.7% (provisional)

22. KPI 5 (Colonoscopy complication rates) 1 st round2 nd round3 rd round (provisional) Admissions Deaths 0.3% 0 0.4% 0 0.4% 0

23. KPI 6 (FOB positivity) 1 st round2 nd round 3 rd round 2.1% 1.9% 1.0% (provisional)

24. KPI 7 (Cancer detection rate /1000 screened) 1 st round2 nd round 3 rd round 2.1 1.2 1.2 (provisional)

25. KPI 8 (Stage at diagnosis) Stage 1 st round2 nd round A 49.2% B 20.3% C1 18.1% C2 2.8% D 7.1% Polyp 17.8% Unknown 2.5% 38.4% 25.8% 20.5% 3.7% 1.9% 12.6% 10.0%

26. Stage Distribution of Symptomatic Colorectal Cancer A8% D25% B33% C34%

27. Stage Distribution of Screen -Detected Cancers True A 26% 48% C26% Polyp Cancers 22% D1% B25%

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 Pre- FOB Post- FOB Adenomas8951102 (+ 23%) Adenocarcinoma410450 (+9.7%) *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 37% 54% 48% 42% P<0.01 * 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 1 st 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) 1 st round2 nd round3 rd round (provisional) Adenomas HR Adenomas 6.5 0.8 5.0 0.5 3.9 0.3

37. KPI 10 (PPV) 1 st round2 nd round3 rd round (provisional) Cancer Adenoma HR Adenoma All Neoplasia 12.0% 36.5% 3.3% 48.5% 6.8% 29.5% 2.9% 36.3% 8.5% 30.1% 3.0% 38.6%

38. Interval Cancers (All cancers diagnosed in the population who responded to the 1 st round screening invitation within 2 years of their FOBT result) Number% Screen-detected35458.4 True Interval18029.7 Missed on colonoscopy 7 1.2 Miscellaneous 6510.7 Total606100

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 Surveillance by FOBt * (or exceptionally colonoscopy at 5 years) Colonoscopy at 3 yearsColonoscopy at 1 year ACB 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 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 High risk (2) Large sessile adenoma removed piecemeal D Check eradication at three months ?re-treat D ? needs surgery Inspect at 1 year No adenoma B Notes:

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 and tissue (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 Immunochemical Testing)

49. FOBt Technology Traditional guaiac tests –Hemoccult, Hema-screen, ColoScreen Sensitive guaiac tests –Hemoccult Sensa, ColoScreen ES Immunochemical tests –InstantView, immunoCARE, Hemosure, Inform, Confirm, Hemascreen Specific

51. FOBt Technology and Cut- off Values Traditional guaiac tests –500-750μg Hb/g faeces Sensitive guaiac tests –300μg Hb/g faeces Immunochemical tests –20-50μg Hb/g faeces –Variable (e.g. OC Sensor)

52. gFOB +ve awaiting colonscopy (n=1600) FIT negative in both [N/N] negative in one and positive in the other [N/P] positive in both [P/P] N/N 346 (21.6%) N/P 258 (16.1%) P/P 996 (62.3%)

53. Positive Guaiac Test (n=1600) %

54. Neg/Neg Immuno Test (n=346) %

55. Neg/Pos Immuno Test (n=258) %

56. Pos/Pos Immuno Test (n=996) % P<0.001

57. Screening algorithm Guaiac FOBT WP [1-4 spots positive] P [5-6 spots positive] Retest FIT N FIT P Investigation = 30% reduction in colonoscopies = 60% reduction in unnecessary colonoscopies

58. “Keeping Scottish Pipes in Tune” (Spot the true Scotsman)