UpdateontheNHS

BowelCancerScreeningProgramme…FocusonBS&FIT

ProfStephenP.Halloran

Estimatedage-standardisedrates/100,000

Men Women

World – Top20Cancers

GLOBOCAN 2012 (IARC)

Incidence& Mortality(2012)

World– ColorectalCancer§ 3rd commonestcancer• 4nd causeofCadeaths

WesternEurope• 2nd commonestcancerdeath• 2nd commonestcancer

• 1st commonestcancerinnon-smokingmen?

IncidenceMortality

Estimatedage-standardisedrates/100,000

Men Women

W.Europe – Top20Cancers

GLOBOCAN 2012 (IARC)

Incidence& Mortality(2012)

World– ColorectalCancer§ 3rd commonestcancer• 4nd causeofCadeaths

WesternEurope• 3nd commonestcancer• 2nd commonestcancerdeath

• 1st commonestcancerinnon-smokingmen?

IncidenceMortality

• Pricewepay… foraffluentlifestyle

• Payaprice… forcancertreatment

Estimatedage-standardisedrates/100,000

Men WomenBowelCancer– Regionalanalysis

GLOBOCAN 2012 (IARC)

Incidence&Mortality (2012)

the bmj | BMJ 2015;351:h4970 | doi: 10.1136/bmj.h4970

RESEARCH

3

Year

Austria

Colo

rect

al ca

ncer

dea

ths

per 1

00 000

peo

ple

0

20

30

40

50

60

10

1970 1980 1990 2000 2010 2020Year

Belarus

1970 1980 1990 2000 2010 2020Year

Belgium

1970 1980 1990 2000 2010

Bulgaria

Colo

rect

al ca

ncer

dea

ths

per 1

00 000

peo

ple

0

20

30

40

50

60

10

Croatia Czech Republic

Denmark

Colo

rect

al ca

ncer

dea

ths

per 1

00 000

peo

ple

0

20

30

40

50

60

10

Estonia Finland

France

Colo

rect

al ca

ncer

dea

ths

per 1

00 000

peo

ple

0

20

30

40

50

60

10

Germany Greece

Hungary

Colo

rect

al ca

ncer

dea

ths

per 1

00 000

peo

ple

0

20

30

40

50

60

10

Iceland Austria

Italy

Colo

rect

al ca

ncer

dea

ths

per 1

00 000

peo

ple

0

20

30

40

50

60

10

Latvia Lithuania

2020

Men Women

Fig 1 | Evolution of colorectal cancer mortality in Europe between 1970 and 2011, by sex (Austria to Lithuania)

doi: 10.1136/bmj.h4970 | BMJ 2015;351:h4970 | the bmj

RESEARCH

4

Year

Luxembourg

0

20

30

40

50

60

10

1970 1980 1990 2000 2010 2020Year

TFYR Macedonia

1970 1980 1990 2000 2010 2020Year

Malta

1970 1980 1990 2000 2010

Netherlands

Colo

rect

al ca

ncer

dea

ths

per 1

00 000

peo

ple

0

20

30

40

50

60

10

Norway Poland

Portugal

Colo

rect

al ca

ncer

dea

ths

per 1

00 000

peo

ple

0

20

30

40

50

60

10

Romania Russian Federation

Slovakia

Colo

rect

al ca

ncer

dea

ths

per 1

00 000

peo

ple

0

20

30

40

50

60

10

Slovenia Spain

Sweden

Colo

rect

al ca

ncer

dea

ths

per 1

00 000

peo

ple

0

20

30

40

50

60

10

Switzerland Ukraine

United Kingdom

Colo

rect

al ca

ncer

dea

ths

per 1

00 000

peo

ple

0

20

30

40

50

60

10

EU-27 United States

2020

Colo

rect

al ca

ncer

dea

ths

per 1

00 000

peo

ple

Men Women

Fig 2 | Evolution of colorectal cancer mortality in Europe between 1970 and 2011, by sex (Luxembourg to USA). EU-27=27 European Union member states

Ouakrim DA,Autier PetalBMJ 2015;351:h4970

Colorectalcancermortality inEurope.Men &Women - 1970and2011

TrendsincolorectalcancermortalityinEurope:retrospectiveanalysisoftheWHOmortalitydatabase

Mortality

Falling

MortalityRising

(PopulationforecastswereextractedfromtheUnitedNations,WorldPopulationprospects,the2012revision)

Predictedincrease intheincidence of

colorectalcancersinEUcountries

from2012to 2025

Alive- 5yearsaftertreatment 93% 77% 7%48%

>50yearsold- 1in4havepolyps 1in10changetoinvasivecancer

10years

Polyp

CancerStage1 2 3 4

ColorectalCancer Pathogenesis

CaseforScreening

ScreeningColonoscopy – 30to45mins• Lookforcancers– removebysurgery• Lookforpolyps– remove bypolypectomy

‘Screeningistheprocessofidentifyinghealthypeople whomaybeatincreasedriskofdisease’

2H2O2 =2H20+O2

Oxidisedguaiaconicacidisblue

Haem GuaiacFOBt

20-25yearsago…FourLargeRandomisedControlledTrialsgFOBT BowelCancerScreening

• Minnesota• Nottingham• Funen• France

Overall16%reductioninmortality

Amongstthosewhodidthetests23%reductioninmortality

ClinicSites

ColonoscopySite

ClinicSites

ClinicSites

ScreeningCentres(18)

SC

SC

SCSC

SC

SC

SC

SC

SC

SC

SCSC

SC

SC

SC

SC

SouthernHub

(Guildford)

ColonoscopySite

BowelCancerScreening

England- July2006

14.6million

ScreeningTimeline

KitReturned

KitRead

+veResult

Patient&GPLetter

-veResult

Patientletter&GPletter/e-message

SSPClinic

AppointmentScreening

Colonoscopy

FreephoneHelpline(

Pre-InvitationAtScreeningDueDate

Day1

InvitationKit&Spatula

ReturnEnvelope

Day8

ReminderLetter

D29

NextPre-Invitation

(1day)

<2days

<14days <14days

NoResponseGPLetter/E-Comms

M3

SurveillanceColonoscopy

2Years

Start2yearlyScreeningCycle

Five-YearNetSurvivalbyAgeEngland 2009-2013

15

England– July2006Phase160- 69yearoldsPhase270– 74Phase3<60

Onceinalifetimeflexisigmoidoscopy

0.0

0.3

0.6

0.9

1.2

Dis

tal c

olon

can

cer:

cum

ulat

ive

inci

denc

e (%

)

0 1 2 3 4 5 6 7 8 9 10 11 12Time from randomisation (years)

ControlScreenedNot Screened

16

Atkinetal.Lancet.2010;375:1624-33

Onceinalifetimeflexisigmoidoscopy

Cumulativeincidencedistalcancer(%)

Outcome- Invited (participated)• Incidencereduction23% (33%)• Mortalityreduction31% (43%)

BowelcancerscreeningFlexiblesigmoidoscopyRCTs

1. AtkinWSetal.Once-onlyflexiblesigmoidoscopy screeninginpreventionofcolorectalcancer:amulticentrerandomised controlledtrial.Lancet2010;375(9726):1624-33.

2. Segnan Netal.Once-onlysigmoidoscopy incolorectalcancerscreening:follow-upfindingsoftheItalianRandomizedControlledTrial– SCORE.JNatl CancerInst2011;103(17):1310-22.Epub 2011/08/20.

3. Schoen REetal.Colorectal-cancerincidenceandmortalitywithscreeningflexiblesigmoidoscopy.NewEnglandJournalofMedicine2012;366(25):2345-57.(PLCOTrial)

4. Holme Øetal.Effectofflexiblesigmoidoscopy screeningoncolorectalcancerincidenceandmortality:arandomizedclinicaltrial.JAMA2014;312(6):606-15.

Reduction in… UK Italy US Norway

Incidence 23% 18% 21% 20%

Mortality 31% 22% 26% 27%

44%attendance(7,439 havecolonoscopy)

‘Relevant’Pathology

About53%response

WorksinNorthernItaly?• InvitetoFSwhen58yearsold

• 19%uptakeofFS• InvitedtodoFITafter6months

• 23%uptakeofFIT• Re-invitedtwicetodoFS- ifnotthenFIT

• Overalluptake@2years…• 40– 42%(FSandFIT)

%UptakeinTaunton&Bristol2013/4

%UptakeinBristol2013/4

0

10

20

30

40

50

60

70

80

Gender Age Area ethnic diversity

Area deprivation

Perc

enta

ge o

f tes

t kits

retu

rned

FOBTkitreturnFirst2.6millioninvitationsinEngland

vonWagnerC,Baio G,Raine R etal. (2011)Int JEpidemiol 40,712-718

%Uptake- 3Episodes(E1,E2&E3)Adherence

57.460.9

66.2

70% 1 in3 61%

2 in3

44% 3 in3

0

10

20

30

40

50

60

70

80

1stEpisode 2ndEpisode 3rdEpisode Atleastonce Atleasttwice Atleast3times

2ndInvitatio

n

1stInvitatio

n

3rdInvitatio

n

FullAd

herence

PoorAdh

eren

ce

VeryPoo

rAdh

eren

ce

SouthernHubData

Adherencetoscreening?

NIHR Programme Grantfor Applied Research

The ASCEND study: Strategies to reduce the social gradient in

bowel cancer screening uptake

Verysmalleffect(0.7%)on…• Uptake…• Socioeconomicgradient

1. ImpactofgeneralpracticeendorsementonthesocialgradientinuptakeinbowelcancerscreeningRaine R,HalloranS,etal.BRITISHJOURNALOFCANCER114(3):321-326

2. Effectsofevidence-basedstrategiestoreducethesocioeconomicgradientofuptakeintheEnglishNHSBowelCancerScreeningProgramme(ASCEND):fourcluster-randomisedcontrolledtrialsWardleJ,HalloranS,etal.LANCET387(10020):751-75920

3. ColorectalcancerscreeninguptakeoverthreebiennialinvitationroundsintheEnglishbowelcancerscreeningprogrammeLoSH,HalloranS etal.2ndDigestive-Disorders-Fed.Conf.,London,,GUT.BMJ.64:A373-A3732015

Bloodinfaeces…stillthebestmarkerforpopulation-based

screening!

Faecal Immunochemical Test (FIT)

HaemGuaiactestgFOBT

Globin(Human)

gFOBt

Outcome

Mean FIT Conc.ug Hb /gfaeces

Positives at

20 ug /gCut-off

Normal 10 (1-20) 6.9%

All adenoma 14 (4-23) 9.3%

Adv. adenoma 81 (37-125) 34.5%

Cancer 170 (89-252)

84.6%

FIT measure of Faecal Haemoglobin Concentration

FIT Concentration relates to disease severity

OC-SENSA MICRO

EndoscopicClassification

MeanFIT Conc.ug Hb /g

faeces

+ve at20 ug /gCut-off

Histology

LGD 27 14.1%HGD 197 50.0%Size

< 10 mm 12 9.0%

≥ 10 mm 99 36.4%Number

< 3 adenoma 14 10.1%

≥ 3 adenoma 65 26.7%

FITPilot

FITPilot

BothHubs• Population27.8m• gFOBTKits=1,126,087• FITKits=40,930

SouthernHubLessDeprivation• Population14.7m• gFOBTKits=588,317• FITKits=21,641

Midlands&NorthWestHubMoreDeprivation• Population13.1m• gFOBTKits=537,770• FITKits=19,289

40%

45%

50%

55%

60%

65%

70%

75%

IMD1(Posh) IMD2 IMD3 IMD4 IMD5(Poor)

gFOBtFIT

40%

45%

50%

55%

60%

65%

70%

75%

IMD1(Posh) IMD2 IMD3 IMD4 IMD5(Poor)

6.7%6.0%

6.8%

8.0%

7.9%

Uptake&Deprivation(IMDIndexofMultiple Deprivation)

2014Pilot

40% 45% 50% 55% 60% 65%

Mid&NW

Southern

Both

FITgFOBt

40% 45% 50% 55% 60% 65%

Mid&NW

Southern

Both

FITgFOBt

10.9%Increase

9.7%

12.2%

1st invitation(mostly60yearoldsubjects)

London38.6% 52.4% 14.4%Increase

UptakeatFirstInvitation2014/5South,Midlands,NW&LondonPilots

0% 5% 10% 15% 20% 25% 30%

Mid&NW

Southern

Both

FITgFOBt

0% 5% 10% 15% 20% 25% 30%

Mid&NW

Southern

Both

FITgFOBt

11.6%Increase

11.8%

11.3%

1– 5invitationsbutno previousresponse

London 9.7%19.5% 9.8%Increase

UptakeinPrevalentEpisodes2014/5South,Midlands,NW&LondonPilots

82% 84% 86% 88% 90% 92%

Mid&NW

Southern

Both

FITgFOBt

82% 84% 86% 88% 90% 92%

Mid&NW

Southern

Both

FITgFOBt

4.2%Increase

4.1%

4.3%

1– 5previousparticipationepisodes

UptakeinIncidentEpisodes2014/5South,Midlands,NW&LondonPilots

50% 55% 60% 65% 70%

Mid&NW

Southern

Both

FITgFOBt

50% 55% 60% 65% 70%

Mid&NW

Southern

Both

FITgFOBt

7.0%

7.1%Increase

7.3%

290,000Additionalscreens

eachyear!

0– 5previousscreeninginvitations

Uptake&AllEpisodes2014South,Midlands,NWPilot

10.1%

8.3%

19.5%

17.5%

30.6%

14.0%

4.0%

FIT20FIT40FIT100FIT150FIT180gFOBT

Cancer

High-riskAdenoma

Low-riskAdenoma

Abnormal

Normal

Intermediate-riskAdenoma

Colonoscopy

FIT180

CancerNormal

High-riskAdenoma

Intermediate-riskAdenoma

Abnormal

Low-riskAdenoma

10.6%

16.5%

18.3%18.6%

23.9%

12.1%

gFOBT

Polypectomy rateincrease>64%with…

…morepolypsineachcategory

Colonoscopy

%Positivity &Deprivation

0.0%

2.0%

4.0%

6.0%

8.0%

10.0%

12.0%

IMD1(Posh) IMD2 IMD3 IMD4 IMD5(Poor)0.0%

2.0%

4.0%

6.0%

8.0%

10.0%

12.0%

IMD1(Posh) IMD2 IMD3 IMD4 IMD5(Poor)0.0%

2.0%

4.0%

6.0%

8.0%

10.0%

12.0%

IMD1(Posh) IMD2 IMD3 IMD4 IMD5(Poor)

FITCut-off- 20ug Hb/gFaeces

0.0%

1.0%

2.0%

3.0%

4.0%

5.0%

6.0%

7.0%

8.0%

9.0%

gFOBt FIT20 FIT40 FIT100 FIT150 FIT180

7.9%

1.7% 1.56%

ug Haemoglobin/gFaeces

FITThreshold and Positivity(BCSPinEngland)

0 20 40 60 80 100 120 140 160 180

Sweden(pilot)AustriaIsrael

NewZealand(pilot)Netherlands(pilot)Switzerland(not…

Belgium(Flanders)Latvia(pilot)

Lithuania(pilot)Australia

England(pilot)UraguayTaiwan

Spain(Catalonia)<20Slovenia

SingaporeMaltaKorea

Italy(North<20)Iceland(planned)

HungaryDenmark

Norway(pilot)PortugalFrance

Canada(Quebec)NewZealand

SouthernIrelandNetherlands

Scotland(Dec.2017)England(April2018)

FaecalImmunochemicalTest(FIT)threshold(ug haemoglobin/gfaeces)

FaecalImmunochemicalTest(FIT)&PositivityThresholdsadoptedbyNationalBowelCancerScreeningProgrammes

(1st October2016)

PredictedFITpositivity- %ofparticipantsreferredforcolonoscopy12% 7.8% 5.2% 2.9% 1.7%2.1% 1.5%

ThresholdusedintheFITpilotinEngland

ColonoscopyCapacityProblems

?

ScreenEpisode&FITthreshold– CancerDetectionRate

0.0%

0.1%

0.2%

0.3%

0.4%

0.5%

0.6%

FIRS

TPR

EVAL

ENT

INCIDE

NT

FIRS

TPR

EVAL

ENT

INCIDE

NT

FIRS

TPR

EVAL

ENT

INCIDE

NT

FIRS

TPR

EVAL

ENT

INCIDE

NT

FIRS

TPR

EVAL

ENT

INCIDE

NT

FIRS

TPR

EVAL

ENT

INCIDE

NT

FIRS

TPR

EVAL

ENT

INCIDE

NT

FIRS

TPR

EVAL

ENT

INCIDE

NT

FIRS

TPR

EVAL

ENT

INCIDE

NT

FIRS

TPR

EVAL

ENT

INCIDE

NT

FIRS

TPR

EVAL

ENT

INCIDE

NT

20 40 60 80 100 120 140 160 180 200 gFOBt

%Can

cerD

etectio

nRa

te

FirstInvitation(60yearolds)NoresponsetopreviousinvitationsParticipatedpreviously

gFOBTFIT

ScreenEpisode&FITthreshold– CancerDetectionRate

0.0%

0.1%

0.2%

0.3%

0.4%

0.5%

0.6%

FIRS

TPR

EVAL

ENT

INCIDE

NT

FIRS

TPR

EVAL

ENT

INCIDE

NT

FIRS

TPR

EVAL

ENT

INCIDE

NT

FIRS

TPR

EVAL

ENT

INCIDE

NT

FIRS

TPR

EVAL

ENT

INCIDE

NT

FIRS

TPR

EVAL

ENT

INCIDE

NT

FIRS

TPR

EVAL

ENT

INCIDE

NT

FIRS

TPR

EVAL

ENT

INCIDE

NT

FIRS

TPR

EVAL

ENT

INCIDE

NT

FIRS

TPR

EVAL

ENT

INCIDE

NT

FIRS

TPR

EVAL

ENT

INCIDE

NT

20 40 60 80 100 120 140 160 180 200 gFOBt

%Can

cerD

etectio

nRa

te

x5.1

x2.5

140

FirstInvitation(60yearolds)NoresponsetopreviousinvitationsParticipatedpreviously

x1

gFOBT60FIT

0.00%

0.05%

0.10%

0.15%

0.20%

0.25%

0.30%

0.35%

0.40%

0.45%

FIT20 FIT100 FIT150 FIT180 gFOBt

CancerDetectio

nRa

te

AgeGroup

Age&FITThreshold– CancerDetectionRate

59-64 65-69 70-75

Sex&FITthreshold– %Positivity

0.0%

1.0%

2.0%

3.0%

4.0%

5.0%

6.0%

7.0%

8.0%

9.0%

10.0%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

0 20 40 60 80 100 120 140 160 180 200 220

%FITPositivity

%M

issed

neo

plasmsrelativetoth

osede

tected

usin

g20ug

/gcu

t-off

FIT(OC-Sensor)Cut-off(ug/g)

PositivityWhyagenderdifference?

• Moredisease• FITmoresensitive

The Power of Quantitative FITMultivariate Risk Scores

• Quantitative FITconcentration

• Age&Sex

• Screeninghistory

• IndicesofDeprivation– Geodemographics (Postcode)

• MedicalHistory – IBD,Crohns,DM,etc

• FamilyHistory– 1st and2nd degreerelatives

• Lifestyle– Smoking,exercise,diet,obesity

MultivariateBowel Cancer

Risk Score

Better PersonalisedPopulation-based Screening!• Positive Predictive Values• Cost Effectiveness• Colonoscopy Referrals

FIT– Anopportunitytopersonalisepopulation-basedscreening?

‘Personalisingpopulation-basedscreening’1. IntelligentuseofFITdata(variablecut-offs)2. IncorporatepersonalriskinaMultivariateRiskScores3. Personalisedinvitationwhichissensitivetosex&screeninghistory

BetterScreeningby-…focusingonindividuals…

...aswellasonpopulations?

FIT4Me ScreeningSystems