Screening strategiesTryggvi Björn Stefánsson

Dept of SurgeryLandspitali University Hospital

WHO criteria for population screening

The condition should be an important health problem.Treatment must exist.Latent or early symptomatic stage.Target population.Test validated and acceptableScientific evidence for program effectiveness (RCT)TrainingQuality control

Wilson and Jungner 1968 and Anne Andermann, Ingeborg Blancquaert, Sylvie Beauchamp, Véronique Déry 2008

The Condition.

Adenomatous Polyp

CRCancer Symptoms

Death

65 – 75 years

5-10 years

5-10 years

Sojourn time

Lead time

Survival time

55 – 65 years

ScreeningScreening

Goals of CRC screening

Detect cancer at an early, curable stage.

Detect and remove adenomatous polyps.

The Tests1) tests that primarily detect Cancer

gFOBT (guaiac-based fecal occult blood testing)FIT (immunochemical-based FOBT) sDNA (testing stool for exfoliated DNA)

2) tests that can detect cancer and advanced lesions.

Double-contrast barium enema. CT colonography.Flexible sigmoidoscopy. Colonoscopy.

gFOBT vs FITgFOBT FITGuiac detects peroxidase

activity.HemePlant peroxidases.Red meatVit CBleeding from all GI

tractSpecial diet for 3 days3 samples

Globin.Human blood.Detects only occult

bleeding from the colon.No dietary interference.1 sample

gFOBTFinland

Sensitivity for CRC: 55%* Specificity : 98%* Compliance: 71%* (23%-78%) FOBT+ 2,1%* Cancer in FOBT+ 8,2%*

Highest sensitivity (50%) in the stage of clinical diagnosis**

Very low sensitivity for precancerous lesions

*H. Paimela et al. BJS 2010** Iris Lansdorp-Vogelaar, Cancer, 2009

FIT

FIT is superior to gFOBT in terms of compliance and detection of CRC and advanced adenomas.

Rabeneck L et al. Can J Gastroenterol 2012.

FIT+ 5,2%Cancer in FOBT+ 6%

High positivity rate, High sensitivity, low specificity .J. Faivre, European Journal of Cancer, 2012.

sDNAStool DNA test: Finds DNA markers for precancerous

lesions and cancers.

Multicentered study from the Mayo clinic:Sensitivity for CRC 85%

Sensitivity for adenomas (≥1 cm) 54%Specificity 90%Still researchExpensive

Ahlquist DA et al, Gastroenterology. 2012 Feb

DCBE

48% sensitivity to detect polyps (> 1cm)compared to colonoscopy. Winawer, Gastroenterology, 2000.

Alternative for those who cannot undergo colonoscopy.

DCBE vs CT colonographyCT colonography: Lower radiation dose than

DCBE. Neri et al Abd Imaging 2010.

Sensitivity SpecificityCT colonogr 83% 86%DCBE 60% 97%

Johnson CD clinical gastroenterol and hepatol

2004

CTC can be done without cleansing (stool tagging)

CT ColonographyPolyps > 10mm

Sensitivity 93%Specificity 97%

Polyps 6-10mmSensitivity 86%Specificity 86%

CancerSensitivity 95,9%

Halligan S et al Radiology 2005

SigmoideoscopyInvestigates 60 cm. Removal of all polyps within 60

cm.

Followed by colonoscopy in case of advanced lesions.

Sensitivity and specificity for polyps and cancer is high.

Sensitivity for advanced lesions and CRC in the whole colon : 60-70% of the sensitivity of a colonoscopy.

Lieberman NEJM 2000

ColonoscopyInvestigates all colon and removal of all

polyps

The main screening method today

Required for confirmation of positive findings from other tests.

Gold standard for assessment of the efficacy of other screening methods.

15

Effectivity of Screening Programs

Incidence Mortality

gFOBT 0 15% * (25%*)FIT ? ?sDNA ? ?DCBE ? ?CT colonography ? ? Sigmoidoscopy 21% (33%) 33% (43%) **Colonoscopy [over 50%] [53%, 65% ]

*Cohrane review, Hewitson P, Am J Gastroenterol. 2008** Wendy Atkins 2010

Colonoscopy Trials Many cohort and case control studies on colonoscopy screening showing over 50%

decrease in incidence and mortality.

Incidence Mortality

Winawer et al NEJM 1993 76%, 88% and 90%

Müller AD et al Ann Int Med 1995 59%

Citarda F et al. Gut 2001 66%

Kahi CJ et alClin Gastroenterol et Hepatol 2009 67% 65%

Brenner H et al. Ann Int Med 2011 77%

Two randomized controlled trials The Spanish trial 55,000 individuals , 50–69 years iFOBT or colonoscopy screening. Started in 2008, results are expected in 2021, after 10 years of follow-up .

TheNordic–European Initiative on Colorectal Cancer (NordICC) multicentre, multinational randomised trial 66,000 individuals colonoscopy or no screening. started screening in 2009. A 15-year follow-up period after screening is

planned,with an interimanalysis after 10 years,due about year 2022

Landspitalinn has been in the NordICC group from the beginning and there has been an interest to contribute to the trial.

Due to opportunistic screening in Reykjavik we are probably not able to take part.

Opportunistic screeningIncreasing !In 10 years ??Are we going to wait for 10 years ?What if there is no difference ?Is it ethical to fight pollution in the control

groups ?The control groups are going to be polluted

whatever we do.

What can we do in Iceland ?Registry for colonoscopies and polyps

(histology)

Improve the quality of the colonoscopies:Training programmes.Quality control (Gastronet).

Start screening.Preferably with colonoscopy.Within the NordICC study.