L. Hol1, E.J.Kuipers1,2

1
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

2
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

3
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
4
CRC Screening in Europe
Screening options

• Guaiac-based FOBT (gFOBT)
• Immunochemical FOBT (FIT)
• Flexible sigmoidoscopy (FS)
• Colonoscopy

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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
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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
7
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
NORCCAP6 Norway 20780 50-64
1 Selby, NEJM 1992 Newcomb NEJM 1992 3UKflex,
Lancet 2002 4Segnan, JNCI 2002 5Weissfeld, JNCI
2005 6Gondal Sacn J G 2003
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CRC Screening in Europe
Colonoscopy screening
1Winawer, NEJM 1993
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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
10
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 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.

7International union against cancer. Brussel
guidelines 2007
11
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 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.

7International union against cancer. Brussel
guidelines 2007
12
CRC Screening in Europe
Nation-wide screening (call/recall)
13
CRC Screening in Europe
Opportunistic programs
14
CRC Screening in Europe
Regional programs
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CRC Screening in Europe
Pilot programs
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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
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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 lt50
Germany gFOBT Colonoscopy Annual Biennial 10-yearly 50-55 55 55 lt20
Poland Colonoscopy 10-yearly 50 lt10
Slovakia Colonoscopy 10-yearly 50 lt30
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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
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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

20
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

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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
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Results (I)
Trial profile
gFOBT
5004 were invited
206 were excluded
4748 were eligible
2374 (50) attended
23
Results (II)
Attendance men / women

Plt0.001
Plt0.001
Univariate analysis
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Results (III)
Findings
Findings during sigmoidoscopy and colonoscopy
Advanced adenoma adenoma 10 mm, villous
component ( 25 villous) or high-grade
dysplasia serrated adenoma three or more
adenomas.
25
Results (V)
Advanced neoplasia per 100 invited
3.0 2.5 2.0 1.5 1.0 0.5 0.0
Advanced neoplasia / 100 invited
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Conclusie
Conclusion (II)
Summary CORERO-trial

• 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

27
CRC Screening in Europe
Main issues of CRC screening in Europe

• Quality assurance (European guidelines)
• Uptake / coverage
• Endoscopy resources

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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

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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
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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
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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
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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
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CRC Screening in Europe
Colonoscopy resources
FIT (2yr) gFOBT (2yr) Sigmo (5yr) Colono (10yr)
2005 2010 2015 2020
2025 Year
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Conclusie
CRC Screening in Europe
Conclusions

• Several initiatives for CRC screening in Europe
• Only one country with a nation-wide screening
  program (call / recall system)
• European guidelines will be available in 2009
• European countries should collaborate for further
  improvement of CRC screening quality

35
CORERO-trial
The team
Gastroenterology Lab Angela Heijens Jan
Francke Martine Ouwendijk Nicolle
Nagtzaam Endoscopy unit Jelle Haringsma Maurice
Laban
Steering Committee Ernst Kuipers Dik
Habbema Monique van Leerdam Marjolein van
Ballegooijen Hanneke van Vuuren Sandra van der
Togt Jaqueline Reijerink Lieke Hol
Advisory board Mrs. I. Joung Mrs. A. Cats J.W.
Coebergh