Algeria Croatia Egypt France Greece Italy Jordan Lebanon Lybia Morocco Portugal Syria Slovenia Spain Tunisi a Turkey Palestine Albania Cyprus Macedonia Malta Mediterranean Task Force for Cancer Control (MTCC) AIMS: To unify efforts to eliminate suffering and reduce mortality of cancer through decreasing incidence of adv. disease
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Algeria CroatiaEgypt France Greece
Italy Jordan Lebanon Lybia Morocco
Portugal Syria Slovenia Spain Tunisia TurkeyPalestine
Albania Cyprus
Macedonia Malta
Mediterranean Task Force for Cancer Control (MTCC)
AIMS: To unify efforts to eliminate suffering and reduce mortality of cancer through decreasing incidence of adv. disease
How screening is crucial in ensuring How screening is crucial in ensuring better cure and improved survival better cure and improved survival
How screening is crucial in ensuring How screening is crucial in ensuring better cure and improved survival better cure and improved survival
Massimo CRESPIMassimo CRESPINational Cancer InstituteNational Cancer Institute
““Regina Elena”, Roma - ItalyRegina Elena”, Roma - Italy
CRC Incidence and Mortality in “Less” and “More” Developed Countries
CRC Incidence and Mortality in “Less” and “More” Developed Countries
Globocan 2002
In brutal figures …
More Developed
Less Developed
Incidence
M 353,390 M 196,037
F 312,341 F 159,664
T 665,731
65.2 %
T 355,70134.8 %
Mortality
M 159,914 M 118,025
F 153,980 F 96,184
T 313,894
59.4%
T 214,20940.6 %
COLON cancer Incidence and Mortality COLON cancer Incidence and Mortality
in Mediterranean areain Mediterranean area
TerminologyTerminologyTerminologyTerminology
PrevalencePrevalenceNumber of subjects diagnosed with a disease Number of subjects diagnosed with a disease (CRC) still alive after (CRC) still alive after xx years (or months) years (or months)
SurvivalSurvivalTime interval between diagnosis and death. Time interval between diagnosis and death. Actuarial survival takes into consideration deaths Actuarial survival takes into consideration deaths by causes different from the index disease.by causes different from the index disease.It’s considered like an ultimate parameter of It’s considered like an ultimate parameter of efficiency of the Health System (timely diagnosis, efficiency of the Health System (timely diagnosis, stage of disease, level of treatment and post-stage of disease, level of treatment and post-treatment care, etc.)treatment care, etc.)
PrevalencePrevalenceNumber of subjects diagnosed with a disease Number of subjects diagnosed with a disease (CRC) still alive after (CRC) still alive after xx years (or months) years (or months)
SurvivalSurvivalTime interval between diagnosis and death. Time interval between diagnosis and death. Actuarial survival takes into consideration deaths Actuarial survival takes into consideration deaths by causes different from the index disease.by causes different from the index disease.It’s considered like an ultimate parameter of It’s considered like an ultimate parameter of efficiency of the Health System (timely diagnosis, efficiency of the Health System (timely diagnosis, stage of disease, level of treatment and post-stage of disease, level of treatment and post-treatment care, etc.)treatment care, etc.)
Prevalence at 5y of CRC patientsPrevalence at 5y of CRC patients
5y prevalence
North America 618,403
Central America 28,350
South America 98,150
Europe 999,612
Africa 38,614
Asia 1,003,456
Australia and Pacific 43,630
(Globocan 2002)
EPICENTRO.ISS.IT
EUROCARE.IT
Eurocare-3 study Annals of Oncology
2003 (Suppl. 5) vol. 14
(Not EU)
(Not EU)
(Not EU)
England
Scotland
Wales
5y survival of CRC from Cancer
Registries
Possible actions for Possible actions for CRC PreventionCRC Prevention
Physical activityEnergy intake
Fresh fruit and vegetableDietary fat
CalciumFiber
Anti-oxidant vitaminesSelenium
SCREENINGAnti-inflammatory drugs
Summary of action with level II or III of evidence
Level II: Obtained from at least one properly designed RCT
Level III: Obtained from a control trial without randomisation, “ “ cohort or case-control analytic studies, “ “ multiple time-series with/without the intervention
Mass screening
protocol under Health authorities
selected population target
covers all degrees of risk
evaluation requiredentry test (FOBTs / CTcolonography?) + 2nd level test (Colonoscopy)
or Colonoscopy as entry test when feasible and accepted
.
.
.
.
.
Opportunistic screening
In volunteers subjects using primary diagnostic test as in screening
Low risk less compliant than high risk
Disadvantage: end-points not evaluable
Ensures further coverage of the population
.
.
.
Reduction in mortalitybut lead time and delay time bias
Improved survivaldown-staging
Reduction in incidencein some cases like cervix and colon-rectum because of pre-cancer lesions
Expected effects of screeningExpected effects of screening
Reduction in mortalitybut lead time and delay time bias
Improved survivaldown-staging
Reduction in incidencein some cases like cervix and colon-rectum because of pre-cancer lesions
Expected effects of screeningExpected effects of screening
CRC screening is feasible:CRC screening is feasible:
by historical methods of proven efficacy and efficiency (G-FOBT)
by actual methods I-FOBT or HeSENSAEndoscopy (invasive, costly, but highly efficient in reducing also incidence by polypectomy)
by methods in development Virtual Colonoscopy
Pill camStool-DNA
by historical methods of proven efficacy and efficiency (G-FOBT)
by actual methods I-FOBT or HeSENSAEndoscopy (invasive, costly, but highly efficient in reducing also incidence by polypectomy)
by methods in development Virtual Colonoscopy
Pill camStool-DNA
FOBTs: for a fair evaluation FOBTs: for a fair evaluation … ... an important … ... an important
definitiondefinition
FOBTs: for a fair evaluation FOBTs: for a fair evaluation … ... an important … ... an important
INCIDENCE AND MORTALITY RATES OF CRCINCIDENCE AND MORTALITY RATES OF CRCBY AGE (x 100,000/YEAR)BY AGE (x 100,000/YEAR)
75%
18%5%1%1%
Sporadic
Familiarity
HNPCC
FAP
Crohn / RCU
Who is atWho is at average risk ? average risk ?
Stool Tests Stool Tests
G-FOBTG-FOBT
ImmunoImmunoFOBTFOBT
sDNAsDNA
Relative efficiency of G-FOBT and I-FOBT Relative efficiency of G-FOBT and I-FOBT for CRC and AA for CRC and AA (330 subj. undergoing OC)(330 subj. undergoing OC)
In most developing nations, Africa, Asia (3.8 billion population), CRC screening is not a priority, resources are limited, awareness still low or restricted to the more affluent (private care)
The preferred and more affordable screening strategy worldwide is FOBT (trend towards iFOBT). Bleeding from worm infestation is a problem in developing countries
Primary TC / FS screening offered only in a few affluent nations (US, UK Germany, Italy, Austria, Luxemburg, Poland), FOBT as alternative
In most developing nations, Africa, Asia (3.8 billion population), CRC screening is not a priority, resources are limited, awareness still low or restricted to the more affluent (private care)
The preferred and more affordable screening strategy worldwide is FOBT (trend towards iFOBT). Bleeding from worm infestation is a problem in developing countries
Primary TC / FS screening offered only in a few affluent nations (US, UK Germany, Italy, Austria, Luxemburg, Poland), FOBT as alternative
SCREENING STRATEGIES AND SCREENING STRATEGIES AND AVAILABLE RESOURCESAVAILABLE RESOURCES
Alternate strategies in low Alternate strategies in low resource settingsresource settings
To aim at familiar / genetic risk for CRCTo aim at familiar / genetic risk for CRC (just few key questions by a health professional)(just few key questions by a health professional)
In subjects aged <45 years (rates on total In subjects aged <45 years (rates on total cases)cases) More
DevelopedLess Developed
Incidence M 3.6 % M 16.4 %
F 3.8 % F 15.4 %
EndoscopyEndoscopy
What is HIGH RISK for CRC: impact offamiliar and hereditary factors
What is HIGH RISK for CRC: impact offamiliar and hereditary factors
0
10
20
30
40
50
60
70
80
90
100
%
Average risk 1 first degreerelative
2 first degreerelatives or 1
less 50 y
HNPCC FAP
Rosalind U. Clinics of North America Gastro. End. 2002Rosalind U. Clinics of North America Gastro. End. 2002
Average risk
High risk
18%5%1%1%
Sporadic
Familiarity
HNPCC
FAP
Crohn / RCU
Who is at high Who is at high risk ?risk ?
25%
COLONOSCOPY
COLONOSCOPY
A specific dedication by General Practitioners is suggested being crucial in selecting subjects, by simple questions, for:
Genetic syndromes Familiar risk
These patients NEED COLONOSCOPY
A specific dedication by General Practitioners is suggested being crucial in selecting subjects, by simple questions, for:
Genetic syndromes Familiar risk
These patients NEED COLONOSCOPY
A bit of culture, a minimal effort, a great yield!A bit of culture, a minimal effort, a great yield!
HOW identify them ?? … by a simple questionHOW identify them ??
Miss rate of Flexible Sigmoidoscopy Miss rate of Flexible Sigmoidoscopy for proximal lesions in subjects with for proximal lesions in subjects with
no-distal lesionsno-distal lesions
Miss rate of Flexible Sigmoidoscopy Miss rate of Flexible Sigmoidoscopy for proximal lesions in subjects with for proximal lesions in subjects with
no-distal lesionsno-distal lesions
Range from 22.8 % to 65 %Range from 22.8 % to 65 %
(results of more than 50 studies)(results of more than 50 studies)
Efficacy of colonoscopy in Efficacy of colonoscopy in reducing incidence of CRCreducing incidence of CRCEfficacy of colonoscopy in Efficacy of colonoscopy in reducing incidence of CRCreducing incidence of CRC
Results of two multi-center studies based on long-term follow-up of asymptomatic subjects after a colonoscopy with polypectomy
US National Polyp Study (prospective) - 76 %
Italian Multicenter Study (retrospective) - 66 %
An alternative screening method
But COMPLIANCE in general population is low
Screening Colonoscopy (OC) in Screening Colonoscopy (OC) in asymptomatic subjectsasymptomatic subjects
Meta-analysis of 10 studies, 68,324 participantsMeta-analysis of 10 studies, 68,324 participants
Screening Colonoscopy (OC) in Screening Colonoscopy (OC) in asymptomatic subjectsasymptomatic subjects
Meta-analysis of 10 studies, 68,324 participantsMeta-analysis of 10 studies, 68,324 participants
Miss rate of right sided CRC by colonoscopy in Ontario in usual clinical
practice (1997 – 2001)
Miss rate of right sided CRC by colonoscopy in Ontario in usual clinical
practice (1997 – 2001)
CRC patients database: 4920 subjects
Missed cancers: 4% by colonoscopy performed between 6 – 36 months beforeCRC diagnosis.
(Byrd RL 1989: missed lesions: 3%)
CRC patients database: 4920 subjects
Missed cancers: 4% by colonoscopy performed between 6 – 36 months beforeCRC diagnosis.
(Byrd RL 1989: missed lesions: 3%)
CRC cannot be completely eliminated CRC cannot be completely eliminated even with very intensive screeningeven with very intensive screening
Bressler B et al 2004Bressler B et al 2004
Risk of CRC after negative colonoscopyRisk of CRC after negative colonoscopyRisk of CRC after negative colonoscopyRisk of CRC after negative colonoscopy
RRRR
OverallOverall 0.550.55
Left colonLeft colon 0.160.16 0.12 – 0.330.12 – 0.33
Right colonRight colon 0.670.67 0.800.80Singh 2009Singh 2009 Ransohoff 2009Ransohoff 2009
Geul K et al, 2007Geul K et al, 2007
About 80% subjects with CRC between 50 – 58y About 80% subjects with CRC between 50 – 58y have already one adenoma at 50yhave already one adenoma at 50y
QUALITY of OC !? QUALITY of OC !? Fast-growing lesions !?Fast-growing lesions !?
QUALITY of OC !? QUALITY of OC !? Fast-growing lesions !?Fast-growing lesions !?
Differences in protection against right/left
sided CRC after a negative index CS ? Differences in protection against right/left
sided CRC after a negative index CS ?
Quality of CSQuality of CS (gastroent. Vs non-gastroent.?)(gastroent. Vs non-gastroent.?)
Flat non polypoid lesionsFlat non polypoid lesions (more in right colon ?)(more in right colon ?)
Biology of proximal lesionBiology of proximal lesion (MSI and CIMP status ?)(MSI and CIMP status ?)
Why women worst ?Why women worst ? (RR 0.99 vs 0.89 men)(RR 0.99 vs 0.89 men)
Quality of CSQuality of CS (gastroent. Vs non-gastroent.?)(gastroent. Vs non-gastroent.?)
Flat non polypoid lesionsFlat non polypoid lesions (more in right colon ?)(more in right colon ?)
Biology of proximal lesionBiology of proximal lesion (MSI and CIMP status ?)(MSI and CIMP status ?)
Why women worst ?Why women worst ? (RR 0.99 vs 0.89 men)(RR 0.99 vs 0.89 men)
Low public compliance to screening colonoscopy Low public compliance to screening colonoscopy (from Jack Tippit, Saturday Evening Post)(from Jack Tippit, Saturday Evening Post)
Ongoing CRC screening activities in Italy 2006Ongoing CRC screening activities in Italy 2006
Regional variations Regional variations
Ongoing CRC screening activities in Italy 2006Ongoing CRC screening activities in Italy 2006
Regional variations Regional variations
M. Zorzi et al 2006 survey - National Centre for Screening Monitoring
Theoretical Theoretical extention #extention #
Actual Actual extension extension (invited)(invited)
NorthNorth 66.1 % 50.2
CenterCenter 48.5 % 22.8
SouthSouth 10.0 % 4.8
# Population covered by organized screening programs
Screened Screened by TCby TC
11.311.3
14.214.2
2.82.8
Compliance to screening tests in Compliance to screening tests in average practice average practice (in the real world !!)(in the real world !!) Compliance to screening tests in Compliance to screening tests in
average practice average practice (in the real world !!)(in the real world !!)
Population based extent of CRC screening Population based extent of CRC screening in Ontario (Canada) in Ontario (Canada)
<20%<20% (Rabeneck L. et al. 2004)(Rabeneck L. et al. 2004)
Participation in colonoscopy population Participation in colonoscopy population screening in Australia screening in Australia
18.2%18.2% (Scott RG et al. 2004)
Population based extent of CRC screening Population based extent of CRC screening in Ontario (Canada) in Ontario (Canada)
<20%<20% (Rabeneck L. et al. 2004)(Rabeneck L. et al. 2004)
Participation in colonoscopy population Participation in colonoscopy population screening in Australia screening in Australia
18.2%18.2% (Scott RG et al. 2004)
??How to increase compliance ?
How to increase compliance ?
The problem is: compliance to any screening test … …
The problem is: compliance to any screening test … …
Sampdoria - Parma Sampdoria - Parma (21 Feb (21 Feb 04)04)
TV: March 2005
Established conceptsEstablished concepts
For For early detectionearly detection and and preventionprevention of CRC and polypsof CRC and polyps
ColonoscopyColonoscopy
For For early detectionearly detection of Advanced neoplasiaof Advanced neoplasia FOBTsFOBTs
In the real world….In the real world….• Uptake of screening opportunities is Uptake of screening opportunities is not exceeding 40 not exceeding 40
to 50%to 50% even in the more developed, wealthy nations even in the more developed, wealthy nations
• In unselected general population it is as In unselected general population it is as low as 20%low as 20% (Australia, Canada)(Australia, Canada)
• The The scarce convincememnt of GPsscarce convincememnt of GPs in advising CRC in advising CRC screening and the screening and the embarassmentembarassment to discuss bowel to discuss bowel matters are problems that only a strong action towards matters are problems that only a strong action towards increased awareness may overcomeincreased awareness may overcome
Results of European / USA RCTs Results of European / USA RCTs based on FOBTbased on FOBT
Results of European / USA RCTs Results of European / USA RCTs based on FOBTbased on FOBT
Europe (4 studies - biennial FOBT - 320,000 subjects) 15 – 18 % reduction in mortality
In subjects complying to all periodic recalls, reduction was 43 %
Early stage were 41 % in intervention arm vs 11% in controls
USA (Minnesota), annual FOBT, reduction in mortality in participating subjects was 55 %
FOBT is the method of choice worldwideFOBT is the method of choice worldwideFOBT is the method of choice worldwideFOBT is the method of choice worldwide
Mortality reduction in the Mortality reduction in the activeactive participating participating
Result: Result: for every 1% increase in for every 1% increase in Colonoscopy Colonoscopy rate, 3% decrease in rate, 3% decrease in CRC mortalityCRC mortality
Result: Result: for every 1% increase in for every 1% increase in Colonoscopy Colonoscopy rate, 3% decrease in rate, 3% decrease in CRC mortalityCRC mortality
Colorectal Cancer (Males) 5y Survival (%)
EPICENTRO.ISS.IT
EUROCARE.IT
Eurocare-3 study Annals of Oncology
2003 (Suppl. 5) vol. 14
CONCLUSIONS CONCLUSIONS i-FOBT (every 12 months) is the best accepted i-FOBT (every 12 months) is the best accepted and affordable at population level (crucial and affordable at population level (crucial awareness by GPs and public)awareness by GPs and public)
CTcolonography is possibly a 1CTcolonography is possibly a 1stst step step substitute, but technical and professional skills substitute, but technical and professional skills are crucialare crucial
A “good” colonoscopy is still the gold standard A “good” colonoscopy is still the gold standard if feasible (health facilities) and accepted if feasible (health facilities) and accepted (awareness)... test of choice in (awareness)... test of choice in high risk high risk subjectssubjects
i-FOBT (every 12 months) is the best accepted i-FOBT (every 12 months) is the best accepted and affordable at population level (crucial and affordable at population level (crucial awareness by GPs and public)awareness by GPs and public)
CTcolonography is possibly a 1CTcolonography is possibly a 1stst step step substitute, but technical and professional skills substitute, but technical and professional skills are crucialare crucial
A “good” colonoscopy is still the gold standard A “good” colonoscopy is still the gold standard if feasible (health facilities) and accepted if feasible (health facilities) and accepted (awareness)... test of choice in (awareness)... test of choice in high risk high risk subjectssubjectsThe best screening test is
the one which is done The best screening test is
the one which is done
Finally . . . Finally . . .
What would you advise as What would you advise as optimal screening test for optimal screening test for yourself or your beloved yourself or your beloved ones ?ones ?
For me: Colonoscopy !!For me: Colonoscopy !!
And for you ???And for you ???
What would you advise as What would you advise as optimal screening test for optimal screening test for yourself or your beloved yourself or your beloved ones ?ones ?