Cribratge de càncer de còlon:

detecció de sang oculta en femta

vs. colonoscòpia

Dr. Antoni Castells

Servei de Gastroenterologia

Hospital Clínic

castells@clinic.cat

Incidència dels càncers més freqüents a Catalunya

Departament de Salut. Desembre 2012

5095

4258

3907

3548

2658

1094

1108

4345

3268

3702

3334

2525

1184

1078

Colon i Recte

Prostata

Mama

Pulmó

Bufeta de l'Orina

Estómac

Linfoma no Hodking

2003-2007 1998-2002

Normal

mucosa Adenoma Carcinoma

Natural history of CRC

Advanced adenoma:

• Size ≥1 cm

• Villous component

• High-grade dysplasia

10 years

Endoscopic polypectomy: CRC mortality

Zauber et al. NEJM 2012

↓Δ 47%

Evidence: 1b

Recommendation: A

CRC screening in average-risk population

Personal

and/or familial

risk factors

No

Age

< 50 years 50 years

No screen Annual or biennial FOBT and/or

sigmoidoscopy / 5 years, o

colonoscopy / 10 years

• U.S. Preventive Services Task Force

• U.S. Multi-Society Task Force on Colorectal Cancer

• American Cancer Society

• AEG – semFYC - Cochrane

1.130

SOH-I anual

SIGMOID. cada 5a

2.305

COLONOSC. cada 10a

2.369

12.647

18.646

Cancer screening: cost-effectiveness

0 €

2.500 €

5.000 €

7.500 €

10.000 €

12.500 €

15.000 €

17.500 €

20.000 €

Cost/QALY

López-Bastida. Servicio Canario de Salud

CRC Prostate Breast Cervical

18.489

Conditions for a population-based

screening (Frame and Carlson, 1975)

Relevant health care problem

Well-established natural history early

detection diminishes morbi-mortality

Effective and well-accepted treatment

Adequate screening test

Cost-effective strategy

Guaiac-based FOBT

FIT

Colonoscopy

CRC screening in Europe

IDCA Survey 2008

Polonia

Republica

Checa Eslovakia

Italia

Luxemburgo

Alemania

Austria

Bulgaria

Finlandia

Francia

Inglaterra

Islandia

Murcia

C. Valenciana

Cataluña

Escocia

Irkanda

Suecia

Dinamarca Letonia

Lituania

Bielorusia

Grecia

Rumanía

Serbia Bosnia

Montenegro

Hungria

Eslovenia

Islas Canarias

1Mandel et al. NEJM 1993 2Hardcastle et al. Lancet 1996 3Kronborg et al. Lancet 1996

-30%

-18%-15%

-35%

-30%

-25%

-20%

-15%

-10%

-5%

0%

Minnesota (1) Nottingham (2) Funen (3)

Reducció de mortalitat per càncer de còlon

Cribratge en població de risc mitjà:

sang oculta en femta (SOF)

Evidència: 1a

Recomanació: A

Van Rossum et al. Gastroenterology 2008

Guaiac

(Hemoccult II®)

Immunològic

(OC-Sensor®) p

Població invitada 10.301 10.322

Restricció dietètica No No

Nombre de mostres 3 1

Participació 4.836 (47%) 6.157 (60%) <0,01

Positivitat prova SOF 2,4% 5,5% <0,01

Adenomes avançats 46 (0,4%) 121 (1,1%) <0,01

Càncer colorectal 11 (0,1%) 24 (0,2%) <0,01

Detecció SOF: guaiac vs. immunològic

Cribratge en població de risc mitjà: colonoscòpia

Baxter et al. Ann Intern Med 2009

Colonoscòpia i reducció de la mortalitat per càncer colorectal

CRC screening in average-risk population

Personal

and/or familial

risk factors

No

Age

< 50 years 50 years

No screen Annual or biennial FOBT and/or

sigmoidoscopy / 5 years, o

colonoscopy / 10 years

• U.S. Preventive Services Task Force

• U.S. Multi-Society Task Force on Colorectal Cancer

• American Cancer Society

• AEG – semFYC - Cochrane

Which one is the best?

Poblacional (organitzat) vs. oportunista

Efectivitat clínica balanç benefici / risc

Evidència científica a favor del model organitzat

Dret a la sanitat activitat d’interès sanitari

Estratègia cost-efectiva mesura de

sostenibilitat del sistema de salut

Cribratge del càncer colorectal

Èxit del cribratge =

sensibilitat de la prova x acceptació

(x accessibilitat)

The ColonPrev Study

Hypothesis

Fecal immunochemical testing (FIT):

Less effective but potentially better accepted

than colonoscopy

Higher acceptance may counteract its lower

efficacy in a population-based approach

FIT-based screening should not be inferior to

colonoscopy-based strategies in terms of CRC-

related mortality in average-risk individuals.

Primary end-point

To compare the efficacy of one-time colonoscopy vs.

biennial FIT for the reduction of CRC-related mortality at

10 years in average-risk population

Secondary end-points

Participation (1st round) and adherence (at 10 years)

rates

Diagnostic rate and diagnostic yield (1st round and

cumulative at 10 years) of advanced colorectal neoplasia

Complication rate (1st round and cumulative at 10 years)

Cost-efficacy

Aims

Study design

Multicenter, randomized controlled trial in 8 Spanish

regions and 15 participating centers

ClinicalTrials.gov number: NCT00906997

Regions with

institutional CRC

population-based

screening program

Regions without

institutional CRC

population-based

screening program

Eligible population

(grouped by address)

Randomization 1:1

Group I: Biennial FIT

(n= 27,749)

Group II: Colonoscopy

(n= 27,749)

Information + invitation ± reminding letters

Appointment: Local Screening Office (questionnaire, post-randomization consent)

Study flow chart

Chronogram

Inclusion period

(1st round)

June

2009

2011

FIT FIT FIT FIT

Analysis of

participation and

detection rate

Screening

(continued)

2021

Analysis of

mortality

Cost-efficacy

Analysis of

CRC incidence

End of 2nd round

Participation and cross-over rates

(intention-to-screen analysis)

24,60%

34,20%

0%

5%

10%

15%

20%

25%

30%

35%

Colonoscopy FIT

p=0.0001

OR, 0.63 (95% CI, 0.60-0.65)

Participation rate

6,20%

0,40%

0%

1%

2%

3%

4%

5%

6%

7%

Colonoscopy > FIT FIT > colonoscopy

p=0.0001

OR, 16.8; 95% CI, 13.9-20.2)

Cross-over rate

Diagnostic yield

(intention-to-screen analysis)

Cancer

0 1 2 3 4 5 6 7 8 9 10 11 12

1.0

FIT Colonoscopy

Odds ratio (adjusted by age, gender and participating center)

30 (0.1%)

33 (0.1%)

2.3 514 (1.9%)

231 (0.9%)

Advanced adenoma

9.8

Non-advanced adenoma

1109 (4.2%)

119 (0.4%)

Colorectal cancer staging

(as-screened analysis)

19

24

66

2

6

0

5

10

15

20

25

Stage I Stage II Stage III

Colonoscopy FIT

p=0.52

Number needed to screen

(per protocol analysis)

191

281

1036

0

50

100

150

200

250

300

Ind

ivid

uals

need

ed

to s

cre

en

Cancer Advanced

neoplasia

Colonoscopy FIT

Number needed to scope

(per protocol analysis)

191

18 102

0

50

100

150

200

250

300

Ind

ivid

uals

need

ed

to s

co

pe

Cancer Advanced

neoplasia

Colonoscopy FIT

Procés de presa de decisions professionals

(multidisciplinar) i ciutadania

Dret a la sanitat

Procés efectiu i cost-efectiu:

Co-responsabilitat del ciutadà

Cal incentivar o afavorir la participació?

Dret a la informació:

Pros (efectivitat) i cons (efectes secundaris)

Respecte al principi d’autonomia

Compartir decisions en el cribratge CCR

Efectes secundaris del cribratge CCR

Morbi-mortalitat

Falsos positius

Falsos negatius càncers d’interval

Falsa seguretat

Sobrediagnòstic sobretractament

Gentilesa: Dr. Josep M Augé (Hospital Clínic)

PDPCCR Barcelona: 100.000 participants

100.000 participants SOF-i positiva (n=6.500)

Gentilesa: Dr. Josep M Augé (Hospital Clínic)

Gentilesa: Dr. Josep M Augé (Hospital Clínic)

100.000 participants Neoplàsia significativa (n=3.061)

Gentilesa: Dr. Josep M Augé (Hospital Clínic)

100.000 participants Càncer colorectal (n=617)

“The best test is the one

that gets done."

Sidney Winawer, MD

Cribratge de càncer de còlon:

detecció de sang oculta en femta

vs. colonoscòpia

Dr. Antoni Castells

Servei de Gastroenterologia

Hospital Clínic

castells@clinic.cat