Gastrolearning II modulo/1a lezione Strategie di screening del cancro Colorettale Prof. C. Hassan - Università Cattolica Sacro Cuore (Roma).

1. STRATEGIE DI SCREENING
DEL
CANCRO COLORETTALE
C. Hassan

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

3. THE PRESENT

4. 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

5. AGE

6. AGE

7. SEX

8. FAMILY HISTORY
•At least one first-degree relative with CRC
CRC RR
2.25
(95% CI:2-2.53)

9. 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)

11. EU GUIDELINES

12. EU GUIDELINES

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

14. OPEN ISSUES
• g-FOBT

15. 329,642 randomized subjects
FU 12-17 yrs.
-25%
-13%
-16%
-16%
RR 0.84
(0.78-0.90)

16. 5.3%
6.4%
33%
2.6%
1.7%
1.7%

17. INCIDENCE
MORTALITY
NS
RR 0.91
(95% CI 84-98%)

18. MORTALITY
-22-32%
NS

19. EU GUIDELINES

20. OPEN ISSUES
• g-FOBT
• FIT

21. g-FOBT vs FIT
•Advanced neoplasia detection rate

22. g-FOBT vs FIT
•Cancer detection rate

23. FIT 1° round vs FIT 2° round

24. 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% !

25. EU GUIDELINES

26. OPEN ISSUES
• g-FOBT
• FIT
• FS

27. May 2010
The BIG BANG
September 2011

28. UK FS
ITT
CRC incidence
-23%
SCORE
-18%
CRC mortality
-31%
-22%

29. UK FS
PP
CRC incidence
-33%
SCORE
-31%
CRC mortality
-43%
-38%

30. INCIDENCE REDUCTION IN THE DISTAL COLON
By year from randomization
SCORE TRIAL
UK FLEXI-SCOPE TRIAL

33. EU GUIDELINES

34. OPEN ISSUES
• g-FOBT
• FIT
• FS
• OC

35. 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

36. 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%

37. OR 0.39
OR 1.07
[0.94─ 1.21] [0.34─ 0.45]
37%

40. HR 10
95% CI 1.4-87

42. Pick up the small (adenoma)
not to miss the BIG (cancer)!
ADR = -Miss Rate Ad. = -Miss Rate CRC

43. 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

44. 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

45. 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

46. 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

47. 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

48. EU GUIDELINES

49. 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

52. OPEN ISSUES
• Is there a variability in colonoscopy-related CRC
prevention rate?
• If any, is such variability related with ADR?

53. OPEN ISSUES
• Are low-risk patients the same as average-risk?

54. Low-risk as average-risk?

55. Low-risk as average-risk?

56. Low-risk as average-risk?
Low-risk = FP

57. Low-risk as average-risk?

58. Low-risk as average-risk?
Risk reduction
TP = >10 mm polypectomy
-60/80%
True FP = negative colonoscopy
-30/70%
TP = <10 mm polypectomy
-0%

59. OPEN ISSUES
• Are low-risk patients the same as average-risk?
• Should we preclude a 1-year examination to
intermediate risk subjects

61. Why 3-years in intermediate risk?

62. CRC risk
0.7%

63. Why 3-years in intermediate risk?

64. Why 3-years in intermediate risk?

65. Why 3-years in intermediate risk?

66. CCE-2 vs FIT
•6% of subjects will result FIT+
•FIT PPV
<30%
•CCE-2 as triage in FIT+

67. 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%

68. CCE-2 vs FS
•10-20% of subjects will result positive at FS
•FS PPV
<20%
•CCE-2 as triage in FS+

69. SEX

70. FAMILY HISTORY
•At least one first-degree relative with CRC
CRC RR
2.25
(95% CI:2-2.53)

71. 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)

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

73. THE PRESENT

74. 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

75. AGE

76. AGE

77. EU GUIDELINES

78. EU GUIDELINES

79. What did we learn from FS trials?
No prevalent
CRC
-66%
Prevalent
CRC
-33%

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