5-6 July 2013, Barcelona
Population-based CRC screening: the FIT approach
Dr Antoni Castells
Director of the Institute of Digestive
Disease, The Hospital Clinic
Barcelona, Spain
Population-based CRCscreening: the FIT approach
Antoni Castells, MD, PhDGastroenterology Department
Hospital Clínic, Barcelona([email protected])
Colorectal cancer prevention
Normalmucosa
Adenoma Carcinoma
Primary prevention
Secondary prevention(screening)
Tertiary prevention(surveillance)
Colorectal cancer: epidemiology
Piñol et al. JAMA 2005
Factores de riesgo personal
y/o familiar
No
Edad
< 50 años ≥≥≥≥ 50 años
AbstenciónCribado
Si
Factor de riesgo personal
Adenoma Enfermedad inflamatoria
intestinal
Vigilancia Vigilancia
Factor de riesgo familiar
PAF CCHNP CCRfamiliar
Cribado
Cribado
Cribado
CRC prevention: risk stratification
0
100
200
300
400
500
20-24 30-34 40-44 50-54 60-64 70-74 80-84
Age (years old)
Ra
te /
10
0.0
00
in
ha
bit
an
ts
Colorectal cancer screening: average-risk population
Conditions for a population-basedscreening (Frame and Carlson, 1975)
� Relevant health care problem
� Well-established natural history ���� early detection diminishes morbi-mortality
� Effective and well-accepted treatment
� Adequate screening test
� Cost-effective strategy
Cancer incidence in Spain
13.212
14.477
15.979
18.821
25.665
0 5.000 10.000 15.000 20.000 25.000 30.000
Próstata
Vejiga
Mama
Pulmón
Colorrectal
Centro Nacional de Epidemiología
Casos nuevos /año
EUROCARE 4
CRC mortality in Spain
Normal mucosa
Adenoma Carcinoma
Natural history of CRC
Advanced adenoma:• Size �1 cm• Villous component• High-grade dysplasia
Advanced adenoma:• Size �1 cm• Villous component• High-grade dysplasia
5 years 5 years
� Mainly located in the proximal colon
� Frequently flat or sessile, covered by mucus
� Predominantly in women, associated with aging
� BRAF mutation, microsatellite instability, CIMP
� Rapidly progressing lesions
Serrated lesions as precursors of CRC
Endoscopic polypectomy: CRC incidence
Winawer et al. NEJM 1993
5
4
3
2
1
4 6 82 años
Incid
en
cia
acu
mu
lad
a
de C
CR
(%
)Polipectomía
SEER
St. Mark
Mayo Clinic
Evidence: 1bRecommendation: A
Endoscopic polypectomy: CRC mortality
Zauber et al. NEJM 2012
�� 47%
CRC screening in average-risk population
Personal and/or familial
risk factors
No
Age
< 50 years ≥≥≥≥ 50 years
No screenAnnual or biennial FOBT and/or
sigmoidoscopy / 5 years, ocolonoscopy / 10 years
• U.S. Preventive Services Task Force• U.S. Multi-Society Task Force on Colorectal Cancer• American Cancer Society• AEG – semFYC - Cochrane
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Cancer screening: cost-effectiveness
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1Mandel et al. NEJM 19932Hardcastle et al. Lancet 19963Kronborg et al. Lancet 1996
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CRC mortality reduction
Screening in average-risk population:fecal occult blood testing (FOBT)
Evidence: 1aRecommendation: A
1970Hemoccult®
Guaiac-based methods
Immunochemical methods (FIT)
Quantitative tests
OC-Sensor®, SENTiFOB®Immudia RPH (Magstream 1000)®
2005
Qualitative testsInmunoCare®FlexSure OBT®Immudia Hem SP®OC-Hemodia®Monohaem®
2000
Qualitative testsInSure®Instant View®Hemeselect, Hemoccult-ICT®OC-Light®
1988Hemoccult-Sensa®
FOBT’s history
Van Rossum et al. Gastroenterology 2008
Guaiac (Hemoccult II®)
FIT
(OC-Sensor®)p
Invitated population 10,301 10,322
Dietary restrictions No No
Stool samples 3 1
Participation –no. (%) 4,836 (47%) 6,157 (60%) <0.01
Test positivity 2.4% 5.5% <0.01
Adv. adenomas –no. (%) 46 (0.4%) 121 (1.1%) <0.01
CRC –no. (%) 11 (0.1%) 24 (0.2%) <0.01
FOBT vs. FIT
Barcelona’s Colorectal CancerScreening Program
Screening in average-risk population:colonoscopy
Baxter et al. Ann Intern Med 2009
Association between colonoscopy and CRC mortality reduction
Evidence: 2bRecommendation: B
CRC screening in average-risk population
Personal and/or familial
risk factors
No
Age
< 50 years ≥≥≥≥ 50 years
No screenAnnual or biennial FOBT and/or
sigmoidoscopy / 5 years, ocolonoscopy / 10 years
• U.S. Preventive Services Task Force• U.S. Multi-Society Task Force on Colorectal Cancer• American Cancer Society• AEG – semFYC - Cochrane
Which one is the best?
The ColonPrev Study
Hypothesis
� Fecal immunochemical testing (FIT):
� Better sensitivity than gFOBT
� Less effective but potentially better accepted than colonoscopy
� Higher acceptance may counteract its lower efficacy in a population-based approach
FIT-based screening should not be inferior to colonoscopy-based strategies in terms of CRC-
related mortality in average-risk individuals.
Primary end-point
� To compare the efficacy of one-time colonoscopy vs. biennial FIT for the reduction of CRC-related mortality at 10 years in average-risk population
Secondary end-points
� Participation (1st round) and adherence (at 10 years) rates
� Diagnostic rate and diagnostic yield (1st round and cumulative at 10 years) of advanced colorectal neoplasia
� Complication rate (1st round and cumulative at 10 years)
� Cost-efficacy
Aims
Study design
Multicenter, randomized controlled trial in 8 Spanish
regions and 15 participating centers
ClinicalTrials.gov number: NCT00906997
Regions withinstitutional CRC population-based screening program
Regions withoutinstitutional CRC population-based screening program
Eligible population(grouped by address)
Randomization 1:1
Group I: Biennial FIT (n= 27,749)
Group II: Colonoscopy(n= 27,749)
Information + invitation � reminding letters
Appointment: Local Screening Office(questionnaire, post-randomization consent)
Study flow chart
Inclusion criteria� Men and women aged 50-69 years
Exclusion criteria
� Personal history of CRC, colorectal adenoma or colorectal polyposis
� Personal history of inflammatory bowel disease
� Family history of colorectal polyposis, Lynch syndrome or familial CRC (>2 FDR with CRC, or 1 FDR with CRC diagnosed <60 years of age)
� Severe comorbidity
� Previous total colectomy
� Not signed informed consent to participate
Methodology (I)
Methodology (II)
� Cross-over between study groups is allowed
� Incomplete colonoscopy: CT-colonography
� Quality-assurance program:
� Colonoscopy
� Recruitment process
� Online database (www.coloncrib.org)
� Communication plan
���������ABCA
Chronogram
Inclusion period(1st round)
June 2009 2011
FIT FIT FIT FIT
Analysis of participation and
detection rate
Screening (continued)
2021
Analysis of mortality
Cost-efficacy
Analysis of CRC incidence
End of 2nd round
Participation and cross-over rates(intention-to-screen analysis)
24,60%
34,20%
0%
5%
10%
15%
20%
25%
30%
35%
Colonoscopy FIT
p=0.0001
OR, 0.63 (95% CI, 0.60-0.65)
Participation rate
6,20%
0,40%
0%
1%
2%
3%
4%
5%
6%
7%
Colonoscopy > FIT FIT > colonoscopy
p=0.0001
OR, 16.8; 95% CI, 13.9-20.2)
Cross-over rate
Diagnostic yield(intention-to-screen analysis)
Cancer
0 1 2 3 4 5 6 7 8 9 10 11 12
1.0
FIT Colonoscopy
Odds ratio(adjusted by age, gender and participating center)
30 (0.1%)33 (0.1%)
2.3514 (1.9%)231 (0.9%)
Advanced adenoma
9.8
Non-advanced adenoma
1109 (4.2%)119 (0.4%)
Colorectal cancer staging(as-screened analysis)
19
24
66
2
6
0
5
10
15
20
25
Stage I Stage II Stage III
Colonoscopy FIT
p=0.52
Number needed to screen(per protocol analysis)
191
281
1036
0
50
100
150
200
250
300
Ind
ivid
uals
need
ed
to s
cre
en
Cancer Advanced
neoplasia
Colonoscopy FIT
Number needed to scope(per protocol analysis)
191
18 10 2
0
50
100
150
200
250
300
Ind
ivid
uals
need
ed
to s
co
pe
Cancer Advanced
neoplasia
Colonoscopy FIT
Summary of ColonPrev results (1st round)
� Subjects in the FIT group were more likely to participate in CRC screening than subjects in the colonoscopy group
� On the baseline screening examination, the number of subjects in whom CRC was detected was similar in the two study groups, but more adenomas were detected in the colonoscopy group
� The comparative effectiveness of FIT and colonoscopy for preventing death from CRC will be assessed at the completion of this 10-year trial
Quintero & Castells et al. N Engl J Med 2012
“The best test is the one that gets done." “The best test is the one that gets done."
Sidney Winawer, MD
Grant support
Local grant support
Population-based CRC screening: the FIT approach
Antoni Castells, MD, PhDGastroenterology Department
Hospital Clínic, Barcelona([email protected])
5-6 July 2013, Barcelona