STRATEGIE DI SCREENING
DEL
CANCRO COLORETTALE
C. Hassan
OPEN ISSUES
• Who should be screened?
• How should we screen?
THE PRESENT
40-4445-5050-5455-5960-6465-6970-7475-79
13.327.655.197.0153.4226.9318.6412.0
4.69.619.034.455.485.6125.9171.9
AGE
Age (years)
CRC incidence/100,000
CRC mortality/100,000
Life-expectancy
4237322824191612
AGE
AGE
SEX
•At least one first-degree relative with CRC
CRC RR 2.25
(95% CI:2-2.53)
FAMILY HISTORY
•At least two first-degree relative with CRC •or one first-degree relative <45 ys
CRC RR: 4.25 (95% CI:3.01-6.02)
FAMILY HISTORY
EU GUIDELINES
EU GUIDELINES
OPEN ISSUES
• Who should be screened?
• How should we screen?
OPEN ISSUES
• g-FOBT
-25%-13%-16%-16%
RR 0.84(0.78-0.90)
329,642 randomized subjects FU 12-17 yrs.
1.7% 1.7%
5.3%6.4%
33%
2.6%
INCIDENCE
NS
MORTALITY
RR 0.91(95% CI 84-98%)
NS
MORTALITY-22-32%
EU GUIDELINES
OPEN ISSUES
• g-FOBT
• FIT
g-FOBT vs FIT
•Advanced neoplasia detection rate
g-FOBT vs FIT
•Cancer detection rate
FIT 1° round vs FIT 2° round
Effetto del test immunologico per la ricerca del sangue occulto fecale sull’incidenza del tumore al colon-retto. Ventura L1, Castiglione G., Grazzini G1, Mantellini P., Romeo G1, Buzzoni C1, Sacchettini C1, Rubeca T1, Zappa M1. 1. ISPO - Istituto per lo Studio e la Prevenzione Oncologica, Firenze
-22% !
EU GUIDELINES
OPEN ISSUES
• g-FOBT
• FIT
• FS
The BIG BANGMay 2010
September 2011
UK FS SCOREITTCRC incidence
-23% -18%
-31% -22%
CRC mortality
UK FS SCOREPPCRC incidence
-33% -31%
-38%
CRC mortality
-43%
INCIDENCE REDUCTION IN THE DISTAL COLON By year from randomization
SCORE TRIAL
UK FLEXI-SCOPE TRIAL
EU GUIDELINES
OPEN ISSUES
• g-FOBT
• FIT
• FS
• OC
Author Population Endpoint Person-years
of follow upFollow up duration (years)
Winawer Post-Polypectomy Incidence 8,401 5.9Citarda Post-Polypectomy Incidence 14,211 10.5Robertson Post-Polypectomy Incidence 10,786 3.7
CRC endpoint reduction
76%66%5%
Variability in colonoscopy efficacyCohort studies
Singh H Negative colon. Incidence 147,781 4.6Lakoff J Negative colon. Mortality 110,402§ 14Brenner H Negative colon. Incidence 6,581 11.9
31%55%100%
Rex Screening Incidence 10,492 14.7 48%
Author Population Endpoint CRC cases
No-CRC
controls
Brenner H Colonoscopy Incidence 1,688 1,932
Brenner H Neg. colonoscopy Incidence 380 485
Muller AD Colonoscopy Incidence 16,351 16,351
Baxter N Colonoscopy Mortality 10,292 51,460
Variability in colonoscopy efficacyCase-control studies
CRC endpoint reduction
77%
74%
45-49%
31%
OR 0.39[0.34─0.45]
OR 1.07[0.94─1.21]
37%
HR 1095% CI 1.4-87
Pick up the small (adenoma)
not to miss the BIG (cancer)!
ADR = -Miss Rate Ad. = -Miss Rate CRC
Author Study design Population Endoscopy
predictors
Biology
Predictors
Predictors of interval CRC
Kaminsky M Cohort Screening Adenoma DR (<20%) NA
Baxter N Cohort Colonoscopy Incompleteness, Polyp DR (<24%), non-GI specialty,
Female sex
Brenner H Case-control Colonoscopy Incompleteness, FOBT+
Female sex, G3-G4
Cooper GS Cohort Medicare Polyp DR (<24%), non-GI, OC Volume
Proximal location
Adenoma Detection Rate dei Servizi di Endoscopia, per utilizzo di sessioni dedicate alle colonscopie di screening (%)
0%
10%
20%
30%
40%
50%
60%
70%
80%
1 4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49 52 55 58 61 64
Ad
enom
a D
etec
tion
Rat
e
sessioni NON dedicate
sessioni dedicate
primo quintile: ADR < 38,6%
quinto quintile: ADR > 51,2%
Modello multilevel per Adenoma DR(LIVELLI: ENDOSCOPISTA, SERVIZIO DI ENDOSCOPIA E REGIONE)
Parametro Odds Ratio 95%IC p value
Caratteristiche del paziente
Sesso del paziente Maschi 1,00 -
Femmine 0,58 0,56-0,60 <0,001
Età del paziente Incremento di un anno
1,02 1,02-1,03 <0,001
Episodio di screening Primo 1,00 -
Successivi 0,78 0,75-0,82 <0,001
Sede raggiunta Colonscopia incompleta
1,00 -
Cieco 2,49 2,29-2,67 <0,001
Preparazione intestinale
Inadeguata 1,00 -
Adeguata 1,52 1,41-1,63 <0,001
Modello multilevel per Adenoma DR(LIVELLI: ENDOSCOPISTA, SERVIZIO DI ENDOSCOPIA E REGIONE)
Parametro Odds Ratio 95%IC p value
Caratteristiche dell’endoscopista
Specializzazione Gastroenterologia 1,00 -
Altro 0,84 0,76-0,92 <0,001
Caratteristiche del Servizio
Sedazione ≤30% dei casi 1,00 -
31%-75% dei casi 1,17 0,89-1,54 0,270
>75% dei casi 1,30 1,01-1,67 0,039
Sessioni dedicate No 1,00 -
Sì 1,29 1,06-1,57 0,010
Adenoma Detection Rate in Servizi di endoscopia con diverse situazioni organizzative, per specialità dell’endoscopista (%)
0%
10%
20%
30%
40%
50%
60%
Sedazione occasionale, sessioni non
dedicate
Sedazione sistematica, sessioni non
dedicate
Sedazione occasionale,
sessioni dedicate
Sedazione sistematica,
sessioni dedicate
Ad
enom
a D
etec
tion
Rat
e
Gastroenterologia
Chirurgia e altre
EU GUIDELINES
CONCLUSIONS
• g-FOBT likely to be replaced by FIT
• FS likely to be added to g-FOBT/FIT
• Colonoscopy implementation will be strictly
related with its quality
OPEN ISSUES
• Is there a variability in colonoscopy-related CRC prevention rate?
• If any, is such variability related with ADR?
OPEN ISSUES
• Are low-risk patients the same as average-risk?
Low-risk as average-risk?
Low-risk as average-risk?
Low-risk as average-risk?
Low-risk = FP
Low-risk as average-risk?
Low-risk as average-risk?
TP = >10 mm polypectomy
True FP = negative colonoscopy
TP = <10 mm polypectomy
-60/80%
-30/70%
-0%
Risk reduction
OPEN ISSUES
• Are low-risk patients the same as average-risk?
• Should we preclude a 1-year examination to intermediate risk subjects
Why 3-years in intermediate risk?
CRC risk0.7%
Why 3-years in intermediate risk?
Why 3-years in intermediate risk?
Why 3-years in intermediate risk?
CCE-2 vs FIT
•FIT PPV <30%
•CCE-2 as triage in FIT+
•6% of subjects will result FIT+
50 60 70 80 90 95+
45 Male
0.149% 0.869% 2.373% 4.387% 5.717% 6.021%
45Fem.
0.130% 0.663% 1.752% 3.434% 4.983% 5.429%
SEX
CCE-2 vs FS
•FS PPV <20%
•CCE-2 as triage in FS+
•10-20% of subjects will result positive at FS
SEX
•At least one first-degree relative with CRC
CRC RR 2.25
(95% CI:2-2.53)
FAMILY HISTORY
•At least two first-degree relative with CRC •or one first-degree relative <45 ys
CRC RR: 4.25 (95% CI:3.01-6.02)
FAMILY HISTORY
OPEN ISSUES
• Who should be screened?
• How should we screen?
THE PRESENT
40-4445-5050-5455-5960-6465-6970-7475-79
13.327.655.197.0153.4226.9318.6412.0
4.69.619.034.455.485.6125.9171.9
AGE
Age (years)
CRC incidence/100,000
CRC mortality/100,000
Life-expectancy
4237322824191612
AGE
AGE
EU GUIDELINES
EU GUIDELINES
No prevalent CRC
Prevalent CRC
What did we learn from FS trials?
-66% -33%
OPEN ISSUES
• Who should be screened?
• How should we screen?