Screening for colorectal cancer
(CRC) in Europe
L. Hol1, E.J.Kuipers1,2
1 Department
of Gastroenterology and Hepatology and
2 Department of Internal Medicine and
Erasmus University Medical Center, Rotterdam.
Hungary, October 17th, 2008
CRC Screening in Europe
Nation-wide screening
Colorectal cancer is the most common malignancy
(380,000/year) and the second most common cancer
related death (180,000/year) in Europe
CRC mortality varies over countries, with Hungary
having the highest mortality rates in Europe and
Greece having the lowest
CRC Screening in Europe
Nation-wide screening
Screening can reduce CRC mortality due to detection
of early carcinomas and removal of pre-malignant
lesions1,2
1Winawer,
NEJM 1993; 2Ries LAG 2007;
CRC Screening in Europe
Screening options
1. Guaiac-based FOBT (gFOBT)
2. Immunochemical FOBT (FIT)
3. Flexible sigmoidoscopy (FS)
4. Colonoscopy
CRC Screening in Europe
Guaiac-based FOBT
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
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
Two case-control studies demonstrated a 60-80%
mortality1,2
Country
Population
Age-group
UKFlex3
UK
354262
55-64
SCORE4
Italy
236.568
55-64
PLCO5
USA
77 465
55-74
Norway
20780
50-64
NORCCAP6
1
Selby, NEJM 1992; Newcomb NEJM 1992
Lancet 2002; 4Segnan, JNCI 2002; 5Weissfeld, JNCI 2005; 6Gondal Sacn J G 2003
3UKflex,
CRC Screening in Europe
Colonoscopy screening
1Winawer,
NEJM 1993;
CRC Screening in Europe
Nation-wide screening
European health council has recommended CRC
screening for average-risk persons aged ≥ 50 years
old with any test6
Today, more than 50% of the target population in the
European Union is however offered no screening at all
Nation-wide screening programs in European
countries vary widely in strategy and quality
guidelines are lacking, hereby hampering efficacy
6Commission
of the European Communities Brussels, 2003
CRC Screening in Europe
Brussel declaration
• 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 highrisk 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 qualityassured 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.
7International
union against cancer. Brussel guidelines 2007
CRC Screening in Europe
Brussel declaration
• 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 highrisk 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 qualityassured 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.
7International
union against cancer. Brussel guidelines 2007
CRC Screening in Europe
Nation-wide screening (call/recall)
CRC Screening in Europe
Opportunistic programs
CRC Screening in Europe
Regional programs
CRC Screening in Europe
Pilot programs
CRC Screening in Europe
Nation-wide program (call/recall)
Country
Test
Interval Age
Participation
England
gFOBT
Biennial
60-69
50-70%
Scotland
gFOBT
Biennial
50-74
CRC Screening in Europe
Nation-wide program (opportunistic)
Country
Test
Interval
Age
Participation
Austria
gFOBT
Sigmoidoscopy
Colonoscopy
Annual
Biennial
5-yearly
10-yearly
50-55
≥ 55
≥ 55
≥ 55
Czech
gFOBT / FIT
Biennial
≥ 50
<50%
Germany
gFOBT
50-55
≥ 55
≥ 55
<20%
Colonoscopy
Annual
Biennial
10-yearly
Poland
Colonoscopy
10-yearly
≥ 50
<10%
Slovakia
Colonoscopy
10-yearly
≥ 50
<30%
CRC Screening in Europe
Regional programs
Country
Test
Interval
Age
Coverage
Finland
gFOBT
Biennial
60-69
France
gFOBT
Biennial
50-74
30-51%
Italy
FIT
Sigmoidoscopy
Both
Biennial
5-yearly
≥ 50
≥ 50
15-70%
Introduction (I)
Pilot program in the Netherlands
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
Introduction (II)
Aim
Primary aim
To determine the attendance rate of guaiac based
faecal occult blood test (gFOBT), immunochemical
FOBT (FIT) and flexible sigmoidoscopy (FS) for CRC
screening.
Secondary objective
To determine the detection rate of advanced
neoplasia and colorectal carcinoma of the three
screening tests
Methods (I)
CORERO-trial
Time frame
November 2006 – November 2007
Design
Population based
Randomised trial
Randomisation Prior to invitation
Per household
Inclusion
Average risk men/women
Screening naïeve
Aged 50-75 years old
Results (I)
Trial profile
gFOB
5004Twere
invited
FIT
FS
5007 were
invited
5000 were
invited
164 were
excluded
206 were
excluded
300 were
excluded
4748 were
eligible
4843 were
eligible
4700 were
eligible
2374
(50%)
attended
2979
(62%)
attended
1522
(32%)
attended
Results (II)
Attendance: men / women
% 100
Men
Women
80
P<0.001
60
P<0.001
40
P=0.01
20
0
46 52
59 64
34 31
gFOBT
FIT
FS
Univariate analysis
Results (III)
Findings
n (%)
gFOBT
FIT
FS*
2351
2975
1386
Positive screening
65 (2.8)
143 (4.8)
142 (10.2)
Colonoscopy
62 (95)
137 (96)
141 (99)
Non-neoplastic polyp
4 (0.2)
7 (0.2)
271 (19.6)
Non-advanced adenoma
9 (0.4)
18 (0.6)
172 (12.4)
Advanced adenoma
25 (1.1)
64 (2.2)
112 (8.1)
CRC
6 (0.3)
14 (0.5)
8 (0.6)
Completed screening
Detection rate / 100 screened
* Findings during sigmoidoscopy and colonoscopy; Advanced adenoma: adenoma ≥ 10 mm,
villous component (≥ 25% villous) or high-grade dysplasia; serrated adenoma; three or more
adenomas.
Results (V)
Advanced neoplasia per 100 invited
P<0.001
3,0
3.0
2.6
2,5
2.5
P<0.001
2.0
2,0
1.6
1.5
1,5
1.0
1,0
0.7
0.5
0,5
0.0
0,0
gFOBT
FIT
FS
Conclusion (II)
Conclusie
Summary
CORERO-trial

FIT screening should be preferred over guaiacbased 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
CRC Screening in Europe
Main issues of CRC screening in Europe
• Quality assurance (European guidelines)
• Uptake / coverage
• Endoscopy resources
CRC Screening in Europe
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
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
8Keighley
M, Eur J Cancer Prev 2004
CRC Screening in Europe
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
9Ladabaum
U, Gatroenterol 2005, 10Butterly L, Am J Prev Med 2007, 11Seeff LC,
Gastroenterol 2004
CRC Screening in Europe
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
Colonoscopy resources
Colonoscopies per 100.000/invitees
6000
5000
4000
FIT
IFobt(2yr)
(2 jr)
gFOBT
Gfobt (2yr)
3000
Sigmo (5
jr)
Sigmo
(5yr)
Colonoscopie
Colono
(10yr)
2000
1000
0
2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024
2005
2010
2015
2020
2025 Year
CRC Screening in Europe
Conclusie
Conclusions
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
CORERO-trial
The team
Steering Committee
Ernst Kuipers
Dik Habbema
Monique van Leerdam
Marjolein van Ballegooijen
Hanneke van Vuuren
Sandra van der Togt
Jaqueline Reijerink
Lieke Hol
Gastroenterology Lab
Angela Heijens
Jan Francke
Martine Ouwendijk
Nicolle Nagtzaam
Endoscopy unit
Jelle Haringsma
Maurice Laban
Advisory board
Mrs. I. Joung
Mrs. A. Cats
J.W. Coebergh