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

Pathology in the UK Bowel Cancer Screening Programmes

Frank Carey

(Dundee)

Screening for Large Bowel Cancer

• Faecal occult blood (FOB)– Guaiac– Immunological

• Sigmoidoscopy

• Colonoscopy

• CT Colography

FOB Screening for colorectal Cancer

• The research

• The pilot

• The programmes

• Pathology

The Research

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

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)(Towler et al 1998)

Effect of Screening onColorectal Cancer Incidence

Control group

Screened groups

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.)

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)

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

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

Key Performance Indicators (KPIs)

1. Uptake– overall– by deprivation category– response rate to first invitation– response rate to reminders

2. Time to colonoscopy3. Proportion of +ves undergoing colonoscopy4. Colonoscopy completion rate5. Colonoscopy complication rate

– admissions– perforations– bleeding– deaths

6. Positivity rate7. Cancer Detection Rate8. 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

KPI 1(Uptake)

1st round 2nd round 3rd round (provisional)

Overall

1st invite

55%

44%

53%

51%

51%

50%

Age and Sex

0

1 0

2 0

3 0

4 0

5 0

6 0

7 0

< 5 5 5 5 - 5 9 6 0 - 6 4 > 6 4

M a l e

F e m a l e

Uptake, %

Age range

Deprivation Category

0

1 0

2 0

3 0

4 0

5 0

6 0

7 0

1 2 3 4 5

Uptake, %

SIMD

KPI 1(Uptake)

2nd round 3rd round(provisional)

Non-responders in previous round

Responders in previous round

14%

85%

13%

87%

KPI 2(Time to colonoscopy)


2 weeks

4 weeks

6 weeks

20%

40%

65%

26%

61%

76%

50%

84%

97%

KPI 3(Proportion of FOBT positive

individuals undergoing colonoscopy)

1st round 2nd round 3rdround

85.5% 85.9% 87.3%

(provisional)

KPI 4(Colonoscopy completion rate)

1st round 2nd round 3rd round

88.0% 90.9% 94.7%

(provisional)

KPI 5 (Colonoscopy complication

rates)1st round 2nd round 3rd round

(provisional)

Admissions

Deaths

0.3%

0

0.4%

0

0.4%

0

KPI 6(FOB positivity)


2.1% 1.9% 1.0%

(provisional)

KPI 7(Cancer detection rate /1000

screened)


2.1 1.2 1.2

(provisional)

KPI 8(Stage at diagnosis)

Stage 1st round 2nd 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%

Stage Distribution of Symptomatic Colorectal Cancer

AA

8%8%DD

25%25%

BB

33%33%CC

34%34%

Stage Distribution of Screen -Detected Cancers

True ATrue A

26%26%

48%48%

CC

26%26%

Polyp CancersPolyp Cancers

22%22%

DD

1%1%

BB

25%25%

Meaning of FOBT +

• Initial positivity 2%. Of these;– 40% have

neoplasia (30% adenoma 10% cancer)

– 10% have something else (eg inflammatory bowel disease)

Colonoscopy Activity at Ninewells Hospital (by

quarter)

0

50

100

150

Screening

Symptomatic

Start of screening

Workload change in Ninewells pathology

Pre-FOB

Post-FOB

Adenomas 895 1102

(+ 23%)

Adenocarcinoma 410 450

(+9.7%)

*Overall effect on colorectal specimen number is not large

• First NHS screening colonoscopy

• Asymptomatic solitary sigmoid polyp (11mm)

• Complete excision of moderately differentiated adenocarcinoma (no lymphatic/vascular invasion)

All Cancers – Screened Health Boards

0

10

20

30

40

50

60

1999-2000 2000-2001

A&B

C&D

37%37%

54%54%48%48%

42%42%

P<0.01

* Screening will save 150 lives per year in Scotland

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

Polyps bleed……..

• About 2900 polyps were removed in the Scottish Pilot 1st round

• Vast majority hyperplastic polyps or adenomas

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

KPI 9(Adenoma detection rate

/1000 screened)1st round 2nd round 3rd round

(provisional)

Adenomas

HR Adenomas

6.5

0.8

5.0

0.5

3.9

0.3

KPI 10(PPV)


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%

Interval Cancers(All cancers diagnosed in the population who

responded to the 1st round screening invitation within 2 years of their FOBT result)

Number %

Screen-detected 354 58.4

True Interval 180 29.7

Missed on colonoscopy 7 1.2

Miscellaneous 65 10.7

Total 606 100

Adenoma Follow-up Scheme

Low risk1 or 2 small adenomas <10mm

Intermediate risk3 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 years Colonoscopy at 1 year

A CB

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:

Pathological measurement of polyp size

Size of polyps round 2

0

100

200

300

400

500

600

1 5 9

13

17

21

25

29

33

37

41

45

49

53

57

61

65

No

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

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

Funding

• New funding available in England (including allocation for pathology)

• Funding contingent on gathering of agreed datasets

• No additional funding in Scotland

Pathology

• Make a diagnosis

• Plan treatment and follow up

• Collect accurate data

• Audit of service development

• Facilitate high quality research

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)

UK Bowel Screening Programs

• Probably the best database on adenoma and early colorectal cancer in the world

• A major opportunity

Role of FIT? (Faecal Immunochemical

Testing)

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

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)

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/NN/N

346 (21.6%)346 (21.6%)

N/PN/P

258 (16.1%)258 (16.1%)

P/PP/P

996 (62.3%)996 (62.3%)

Positive Guaiac Test(n=1600)

0

1 0

2 0

3 0

4 0

5 0

6 0

C a n c e r H i g h - r i s ka d e n o m a

L o w - r i s ka d e n o m a

N o r m a l

%

Neg/Neg Immuno Test(n=346)

0

1 0

2 0

3 0

4 0

5 0

6 0

7 0

8 0



N o r m a l

%

Neg/Pos Immuno Test(n=258)

0

1 0

2 0

3 0

4 0

5 0

6 0

7 0



N o r m a l

%

Pos/Pos Immuno Test(n=996)

0

5

1 0

1 5

2 0

2 5

3 0

3 5



N o r m a l

%

P<0.001

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

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

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

Documents

Transcript of Pathology in the UK Bowel Cancer Screening Programmes Frank Carey (Dundee)