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STRATEGIE DI SCREENING
DEL
CANCRO COLORETTALE
C. Hassan
OPEN ISSUES

• Who should be screened?
• How should we screen?
THE PRESENT
AGE
Age
(years)
40-44
45-50
50-54
55-59
60-64
65-69
70-74
75-79

CRC
incidence
13.3
27.6
55.1
97.0
153.4
226.9
318.6
412.0

/100,000

CRC
mortality
4.6
9.6
19.0
34.4
55.4
85.6
125.9
171.9

/100,000

Lifeexpectancy
42
37
32
28
24
19
16
12
AGE
AGE
SEX
FAMILY HISTORY
•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)
Strategie di screening del cancro Colorettale - Gastrolearning®
EU GUIDELINES
EU GUIDELINES
OPEN ISSUES

• Who should be screened?
• How should we screen?
OPEN ISSUES

• g-FOBT
329,642 randomized subjects

FU 12-17 yrs.

-25%
-13%
-16%
-16%

RR 0.84

(0.78-0.90)
5.3%
6.4%
33%
2.6%

1.7%

1.7%
INCIDENCE

MORTALITY

NS

RR 0.91
(95% CI 84-98%)
MORTALITY
-22-32%
NS
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
May 2010

The BIG BANG

September 2011
UK FS

ITT
CRC incidence

-23%

SCORE

-18%

CRC mortality

-31%

-22%
UK FS

PP
CRC incidence

-33%

SCORE

-31%

CRC mortality

-43%

-38%
INCIDENCE REDUCTION IN THE DISTAL COLON
By year from randomization
SCORE TRIAL
UK FLEXI-SCOPE TRIAL
Strategie di screening del cancro Colorettale - Gastrolearning®
Strategie di screening del cancro Colorettale - Gastrolearning®
EU GUIDELINES
OPEN ISSUES

• g-FOBT
• FIT
• FS
• OC
Variability in colonoscopy efficacy
Cohort studies
Author

Population

Endpoint Person-years Follow up
CRC
of follow up duration endpoint
(years)
reduction

Winawer Post-Polypectomy
Citarda
Post-Polypectomy
Robertson Post-Polypectomy

Incidence

Singh H
Negative colon.
Lakoff J Negative colon.
Brenner H Negative colon.

Incidence

Rex

Screening

8,401
14,211
10,786

5.9
10.5
3.7

76%
66%
5%

Incidence

147,781
110,402§
6,581

4.6
14
11.9

31%
55%
100%

Incidence

10,492

14.7

48%

Incidence
Incidence

Mortality
Variability in colonoscopy efficacy
Case-control studies
Author

Population

Endpoint

CRC
cases

NoCRC endpoint
CRC
reduction
controls

Brenner H
Brenner H

Colonoscopy
Incidence
Neg. colonoscopy Incidence

1,688
380

Muller AD
Baxter N

Colonoscopy
Colonoscopy

16,351 16,351
10,292 51,460

Incidence
Mortality

1,932
485

77%
74%
45-49%
31%
OR 0.39
OR 1.07
[0.94─ 1.21] [0.34─ 0.45]
37%
Strategie di screening del cancro Colorettale - Gastrolearning®
Strategie di screening del cancro Colorettale - Gastrolearning®
HR 10
95% CI 1.4-87
Strategie di screening del cancro Colorettale - Gastrolearning®
Pick up the small (adenoma)
not to miss the BIG (cancer)!
ADR = -Miss Rate Ad. = -Miss Rate CRC
Predictors of interval CRC
Author

Study design

Cohort

Brenner H

Case-control

Cooper GS

Cohort

Baxter N

Cohort

Screening

Endoscopy

Biology

predictors
Kaminsky M

Population

Predictors

Adenoma DR (<20%)

NA

Colonoscopy Incompleteness,
FOBT+
Medicare

Polyp DR (<24%),
non-GI, OC Volume

Colonoscopy Incompleteness,
Polyp DR (<24%),
non-GI specialty,

Female sex,
G3-G4
Proximal
location
Female sex
Adenoma Detection Rate dei Servizi di Endoscopia, per utilizzo di
sessioni dedicate alle colonscopie di screening (%)
80%
70%
60%
quinto quintile: ADR > 51,2%

50%
40%
primo quintile: ADR < 38,6%
R
i
c
t
D
a
m
o
n
e
d
A

30%
sessioni NON dedicate

20%

sessioni dedicate

10%
0%
1

4

7

10 13 16 19 22 25 28 31 34 37 40 43 46 49 52 55 58 61 64
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

1,02

1,02-1,03

<0,001

Età del paziente

Incremento di un
anno
Episodio di screening Primo

1,00

Successivi

Preparazione
intestinale

0,78

Colonscopia
incompleta

2,49

Inadeguata

1,00

Adeguata

1,52

-

1,00

Cieco

Sede raggiunta

-

0,75-0,82

<0,001
-

2,29-2,67

<0,001
-

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

1,00

31%-75% dei casi

1,17

0,89-1,54 0,270

>75% dei casi
Sessioni dedicate

≤30% dei casi

-

1,30

1,01-1,67 0,039

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 (%)
60%
50%
40%
30%
Gastroenterologia
R
i
c
t
D
a
m
o
n
e
d
A

20%
Chirurgia e altre

10%
0%
Sedazione
occasionale,
sessioni non
dedicate

Sedazione
sistematica,
sessioni non
dedicate

Sedazione
occasionale,
sessioni
dedicate

Sedazione
sistematica,
sessioni
dedicate
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
Strategie di screening del cancro Colorettale - Gastrolearning®
Strategie di screening del cancro Colorettale - Gastrolearning®
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?
Risk reduction
TP = >10 mm polypectomy

-60/80%

True FP = negative colonoscopy

-30/70%

TP = <10 mm polypectomy

-0%
OPEN ISSUES
• Are low-risk patients the same as average-risk?
• Should we preclude a 1-year examination to
intermediate risk subjects
Strategie di screening del cancro Colorettale - Gastrolearning®
Why 3-years in intermediate risk?
CRC risk
0.7%
Why 3-years in intermediate risk?
Why 3-years in intermediate risk?
Why 3-years in intermediate risk?
CCE-2 vs FIT
•6% of subjects will result FIT+
•FIT PPV

<30%

•CCE-2 as triage in FIT+
SEX

50

60

70

80

45
Male

0.149%

0.869%

2.373%

45
Fem.

0.130%

0.663%

1.752% 3.434%

90

4.387% 5.717%

95+
6.021%

4.983% 5.429%
CCE-2 vs FS
•10-20% of subjects will result positive at FS
•FS PPV

<20%

•CCE-2 as triage in FS+
SEX
FAMILY HISTORY
•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)
OPEN ISSUES

• Who should be screened?
• How should we screen?
THE PRESENT
AGE
Age
(years)
40-44
45-50
50-54
55-59
60-64
65-69
70-74
75-79

CRC
incidence
13.3
27.6
55.1
97.0
153.4
226.9
318.6
412.0

/100,000

CRC
mortality
4.6
9.6
19.0
34.4
55.4
85.6
125.9
171.9

/100,000

Lifeexpectancy
42
37
32
28
24
19
16
12
AGE
AGE
EU GUIDELINES
EU GUIDELINES
What did we learn from FS trials?

No prevalent
CRC

-66%

Prevalent
CRC

-33%
OPEN ISSUES

• Who should be screened?
• How should we screen?

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