Screening for colorectal cancer (CRC) in Europe

L. Hol1, E.J.Kuipers1,2

1 Department of Gastroenterology and Hepatology and2 Department of Internal Medicine and

Erasmus University Medical Center, Rotterdam.

Hungary, October 17th, 2008

Colorectal cancer is the most common malignancy(380,000/year) and the second most common cancerrelated death (180,000/year) in Europe

CRC mortality varies over countries, with Hungaryhaving the highest mortality rates in Europe andGreece having the lowest

Nation-wide screeningCRC Screening in Europe

Screening can reduce CRC mortality due to detectionof early carcinomas and removal of pre-malignantlesions1,2

Nation-wide screeningCRC Screening in Europe

1Winawer, NEJM 1993; 2Ries LAG 2007;

1. Guaiac-based FOBT (gFOBT)

2. Immunochemical FOBT (FIT)

3. Flexible sigmoidoscopy (FS)

4. Colonoscopy

Screening optionsCRC Screening in Europe

Study Age range mortality

Nottingham1 45-75 13% 11 years

Funen2 45-74 11% 17 years

Minnesota3 50-80 21% 18 years

Goteborg4 60-64 16% 15.5 years

Guaiac-based FOBTCRC Screening in Europe

1Mandel JS, NEJM 1993; 2Kronborg O, Lancet 1996; 3Hardcastle JD, Lancet 1996; Kewenter, Scan J Gastroenterol 1994

FOBT Performance Characteristics

Positivity Rate

Specificity (Neoplasia)

Sensitivity (CRC)

Hemoccult II1 2.5 98.1 37.1

Heme Select2 5.9 95.2 68.8

OC-Hemodia3 6.5 94.0 88.9

*In a screening-naïve population; ** Estimated specificity and sensitivity

1Petrelli N, Surg Oncol 1994; 2Allison JE, NEJM 1996; 3Nakama H, Eur J Cancer 2001

Sigmoidoscopy screening

Country Population Age-group

UKFlex3 UK 354262 55-64

SCORE4 Italy 236.568 55-64

PLCO5 USA 77 465 55-74

NORCCAP6 Norway 20780 50-64

Two case-control studies demonstrated a 60-80% mortality1,2

1 Selby, NEJM 1992; Newcomb NEJM 19923UKflex, Lancet 2002; 4Segnan, JNCI 2002; 5Weissfeld, JNCI 2005; 6Gondal Sacn J G 2003

Colonoscopy screeningCRC Screening in Europe

1Winawer, NEJM 1993;

European health council has recommended CRCscreening for average-risk persons aged ≥ 50 yearsold with any test6

Today, more than 50% of the target population in theEuropean Union is however offered no screening at all

Nation-wide screening programs in Europeancountries vary widely in strategy and qualityguidelines are lacking, hereby hampering efficacy

Nation-wide screening

6Commission of the European Communities Brussels, 2003

CRC Screening in Europe

• Set up an European action plan. • Provide European health ministers with an European guideline for CRC

screening. • Include practical assistance in the detection and management of high-

risk groups. • Include a demand for provision of all target groups with adequate

information. • Implement any national screening programme using call/recall system

through a central agency. • Implement any national screening programme based on quality-

assured and quality-controlled infrastructure. • Advise the member states to facilitate the provision of appropriate

training to personnel involved in screening, processing of results and subsequent treatment.

• Establish and fund designated research programmes for the development and evaluation of programmes for CRC screening.

Brussel declaration

7International union against cancer. Brussel guidelines 2007

CRC Screening in Europe

• Set up an European action plan. • Provide European health ministers with a European guideline for CRC

screening. • Include practical assistance in the detection and management of high-

risk groups. • Include a demand for provision of all target groups with adequate

information. • Implement any national screening programme using call/recall system

through a central agency. • Implement any national screening programme based on quality-

assured and quality-controlled infrastructure. • Advise the member states to facilitate the provision of appropriate

training to personnel involved in screening, processing of results and subsequent treatment.

• Establish and fund designated research programmes for the development and evaluation of programmes for CRC screening.

Brussel declaration

7International union against cancer. Brussel guidelines 2007

CRC Screening in Europe

Nation-wide screening (call/recall)CRC Screening in Europe

Opportunistic programsCRC Screening in Europe

Regional programsCRC Screening in Europe

Pilot programsCRC Screening in Europe

Country Test Interval Age Participation

England gFOBT Biennial 60-69 50-70%

Scotland gFOBT Biennial 50-74

Nation-wide program (call/recall)CRC Screening in Europe

Country Test Interval Age Participation

Austria gFOBT

SigmoidoscopyColonoscopy

AnnualBiennial5-yearly10-yearly

50-55≥ 55≥ 55≥ 55

Czech gFOBT / FIT Biennial ≥ 50 <50%

Germany gFOBT

Colonoscopy

AnnualBiennial10-yearly

50-55≥ 55≥ 55

<20%

Poland Colonoscopy 10-yearly ≥ 50 <10%

Slovakia Colonoscopy 10-yearly ≥ 50 <30%

Nation-wide program (opportunistic)CRC Screening in Europe

Country Test Interval Age Coverage

Finland gFOBT Biennial 60-69

France gFOBT Biennial 50-74 30-51%

Italy FITSigmoidoscopyBoth

Biennial5-yearly

≥ 50≥ 50

15-70%

Regional programsCRC Screening in Europe

Pilot program in the NetherlandsIntroduction (I)

2001 Dutch Health council: CRC screening should be considered.

2006 Start pilot studies

2008 Dutch Health council: Nation-wide CRC screening program most likely based

on FIT will be introduced in the Netherlands in 2010.

Studies on endoscopic screening are needed

Primary aimTo determine the attendance rate of guaiac basedfaecal occult blood test (gFOBT), immunochemicalFOBT (FIT) and flexible sigmoidoscopy (FS) for CRCscreening.

Secondary objectiveTo determine the detection rate of advanced neoplasia and colorectal carcinoma of the three screening tests

AimIntroduction (II)

Time frame November 2006 – November 2007

CORERO-trialMethods (I)

Design Population basedRandomised trial

Randomisation Prior to invitationPer household

Inclusion Average risk men/womenScreening naïeveAged 50-75 years old

Trial profileResults (I)

gFOBT5004 were

invited

206 were excluded

4748 were eligible

2374 (50%)

attended

FIT

5007 were invited

4843 were eligible

2979 (62%)

attended

164 were excluded

FS5000 were

invited

1522 (32%)

attended

4700 were eligible

300 were excluded

52 64 313459460

20

40

60

80

100

gFOBT FIT FS

Men

Women

%

Attendance: men / women

P=0.01

Results (II)

P<0.001

P<0.001

Univariate analysis

Findings Results (III)

n (%) gFOBT FIT FS*

Completed screening

Positive screening

Colonoscopy

2351

65 (2.8)

62 (95)

2975

143 (4.8)

137 (96)

1386

142 (10.2)

141 (99)

Detection rate / 100 screened

Non-neoplastic polyp

Non-advanced adenoma

Advanced adenoma

CRC

4 (0.2)

9 (0.4)

25 (1.1)

6 (0.3)

7 (0.2)

18 (0.6)

64 (2.2)

14 (0.5)

271 (19.6)

172 (12.4)

112 (8.1)

8 (0.6)

* Findings during sigmoidoscopy and colonoscopy; Advanced adenoma: adenoma ≥ 10 mm, villous component (≥ 25% villous) or high-grade dysplasia; serrated adenoma; three or more adenomas.

Advanced neoplasia per 100 invited

2.6

1.6

0.7

0,0

0,5

1,0

1,5

2,0

2,5

3,0

gFOBT FIT FS

Results (V)

Advanc e

d n

eopla

sia /

10

0 invit

ed 3.0

2.5

2.0

1.5

1.0

0.5

0.0

P<0.001

P<0.001

Conclusie

FIT screening should be preferred over guaiac-based FOBT screening

Sigmoidoscopy screening seems to be most effective, but RCTs have to be awaited to determine the CRC incidence and mortality reduction due to FS screening

Summary CORERO-trialConclusion (II)

Main issues of CRC screening in EuropeCRC Screening in Europe

• Quality assurance (European guidelines)

• Uptake / coverage

• Endoscopy resources

Quality assurance

Four out of ten nation-wide programs do not have national guidelines for CRC screening

European guidelines are currently being made (IARC)- Organisation - Evaluation and interpretation of screening outcomes- Quality assurance for endoscopy- Professional requirements and training- Quality assurance for pathology- Management of screen detected lesions- Surveillance

CRC Screening in Europe

Uptake / coverage

Uptake of CRC screening is generally low

High attendance is a prerequisite for an effective colorectal cancer (CRC) screening program

A recall system is preferable over opportunistic screening7

7International union against cancer. Brussel guidelines 2007

CRC Screening in Europe

Public awareness

8Keighley M, Eur J Cancer Prev 2004

CRC Screening in Europe

Willingness to be screened depends on awareness of colorectal cancer and CRC screening

A survey among people in the target population in 21 European countries showed8

• 51% had knowledge of CRC screening • 75% were 'very', or 'quite interested’, in taking up faecal occult blood (FOB) screening if offered free• Lack of awareness of risk (31%) was a main barrier to CRC screening

Endoscopy resources

No solid data on endoscopy resources in Europe Endoscopy capacity varies per region9,10,11

Required resources depend on• Target population• Screening test (positivity rate)• Screening interval• Attendance rate• Guidelines for surveillance

CRC Screening in Europe

9Ladabaum U, Gatroenterol 2005, 10Butterly L, Am J Prev Med 2007, 11Seeff LC, Gastroenterol 2004

Positivity rate

Cut-off % Positive

Grazzini, 2004 100ng 5.8

Segnan, 2005 100ng 4.6

Segnan, 2007 100ng 4.7

Guittet, 2007 75ng 2.4

Van Rossum, 2008 100ng 5.5

Hol, 2008 100ng 4.8

CRC Screening in Europe

0

1000

2000

3000

4000

5000

6000

2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024

Col

onos

copi

es p

er 1

00.0

00/in

vite

es

IFobt (2 jr)

Gfobt

Sigmo (5 jr)

Colonoscopie

Colonoscopy resources

FIT (2yr)

gFOBT (2yr)

Sigmo (5yr)

Colono (10yr)

2005 2010 2015 2020 2025 Year

CRC Screening in Europe

Conclusie

1. Several initiatives for CRC screening in Europe

2. Only one country with a nation-wide screening program (call / recall system)

3. European guidelines will be available in 2009

4. European countries should collaborate for further improvement of CRC screening quality

ConclusionsCRC Screening in Europe

The team

Gastroenterology LabAngela HeijensJan FranckeMartine OuwendijkNicolle Nagtzaam

Endoscopy unitJelle HaringsmaMaurice Laban

CORERO-trial

Steering CommitteeErnst KuipersDik HabbemaMonique van LeerdamMarjolein van BallegooijenHanneke van VuurenSandra van der TogtJaqueline ReijerinkLieke Hol

Advisory boardMrs. I. JoungMrs. A. CatsJ.W. Coebergh