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?