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Transcript of Update on the NHS Bowel Cancer Screening Programme … Day presentations... · • Invite to FS...
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UpdateontheNHS
BowelCancerScreeningProgramme…FocusonBS&FIT
ProfStephenP.Halloran
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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?
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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?
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IncidenceMortality
• Pricewepay… foraffluentlifestyle
• Payaprice… forcancertreatment
Estimatedage-standardisedrates/100,000
Men WomenBowelCancer– Regionalanalysis
GLOBOCAN 2012 (IARC)
Incidence&Mortality (2012)
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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
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(PopulationforecastswereextractedfromtheUnitedNations,WorldPopulationprospects,the2012revision)
Predictedincrease intheincidence of
colorectalcancersinEUcountries
from2012to 2025
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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
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‘Screeningistheprocessofidentifyinghealthypeople whomaybeatincreasedriskofdisease’
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2H2O2 =2H20+O2
Oxidisedguaiaconicacidisblue
Haem GuaiacFOBt
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20-25yearsago…FourLargeRandomisedControlledTrialsgFOBT BowelCancerScreening
• Minnesota• Nottingham• Funen• France
Overall16%reductioninmortality
Amongstthosewhodidthetests23%reductioninmortality
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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
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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
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Five-YearNetSurvivalbyAgeEngland 2009-2013
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15
England– July2006Phase160- 69yearoldsPhase270– 74Phase3<60
Onceinalifetimeflexisigmoidoscopy
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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%)
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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%
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44%attendance(7,439 havecolonoscopy)
‘Relevant’Pathology
About53%response
WorksinNorthernItaly?• InvitetoFSwhen58yearsold
• 19%uptakeofFS• InvitedtodoFITafter6months
• 23%uptakeofFIT• Re-invitedtwicetodoFS- ifnotthenFIT
• Overalluptake@2years…• 40– 42%(FSandFIT)
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%UptakeinTaunton&Bristol2013/4
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%UptakeinBristol2013/4
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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
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%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?
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NIHR Programme Grantfor Applied Research
The ASCEND study: Strategies to reduce the social gradient in
bowel cancer screening uptake
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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
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Bloodinfaeces…stillthebestmarkerforpopulation-based
screening!
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Faecal Immunochemical Test (FIT)
HaemGuaiactestgFOBT
Globin(Human)
gFOBt
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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%
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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
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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
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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
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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
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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
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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
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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
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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
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%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
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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)
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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
?
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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
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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
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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
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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
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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
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FIT– Anopportunitytopersonalisepopulation-basedscreening?
‘Personalisingpopulation-basedscreening’1. IntelligentuseofFITdata(variablecut-offs)2. IncorporatepersonalriskinaMultivariateRiskScores3. Personalisedinvitationwhichissensitivetosex&screeninghistory
BetterScreeningby-…focusingonindividuals…
...aswellasonpopulations?
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FIT4Me ScreeningSystems