Tryggvi Björn Stefánsson Dept of Surgery Landspitali 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 acceptable Scientific evidence for program effectiveness (RCT) Training Quality control Wilson and Jungner 1968 and Anne Andermann, Ingeborg Blancquaert, Sylvie Beauchamp, Véronique Déry 2008

The Condition. Adenomatous Polyp CRCancerSymptoms Death 65 – 75 years 5-10 years Sojourn time Lead time Survival time 55 – 65 years Screening

Goals of CRC screening Detect cancer at an early, curable stage. Detect and remove adenomatous polyps.

The Tests 1) 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 FIT gFOBT FIT Guiac detects peroxidase activity. Heme Plant peroxidases. Red meat Vit C Bleeding from all GI tract Special diet for 3 days 3 samples Globin. Human blood. Detects only occult bleeding from the colon. No dietary interference. 1 sample

gFOBT Finland 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 FIT+5,2% Cancer in FOBT+6% High positivity rate, High sensitivity, low specificity. J. Faivre, European Journal of Cancer, 2012.

sDNA Stool DNA test: Finds DNA markers for precancerous lesions and cancers. Multicentered study from the Mayo clinic: Sensitivity for CRC85% Sensitivity for adenomas (≥1 cm)54% Specificity90% Still research Expensive Ahlquist DA et al, Gastroenterology Feb

DCBE 48% sensitivity to detect polyps (> 1cm)compared to colonoscopy. Winawer, Gastroenterology, Alternative for those who cannot undergo colonoscopy.

DCBE vs CT colonography CT colonography: Lower radiation dose than DCBE. Neri et al Abd Imaging SensitivitySpecificity CT colonogr83%86% DCBE60%97% Johnson CD clinical gastroenterol and hepatol 2004 CTC can be done without cleansing (stool tagging)

CT Colonography Polyps > 10mm Sensitivity 93% Specificity 97% Polyps 6-10mm Sensitivity 86% Specificity 86% Cancer Sensitivity 95,9% Halligan S et al Radiology 2005

Sigmoideoscopy Investigates 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

Colonoscopy Investigates 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.

Effectivity of Screening Programs IncidenceMortality gFOBT015% * (25%*) FIT?? sDNA?? DCBE?? CT colonography?? Sigmoidoscopy21% (33%)33% (43%) ** Colonoscopy[over 50%][53%, 65% ] *Cohrane review, Hewitson P, Am J Gastroenterol ** Wendy Atkins

Colonoscopy Trials Many cohort and case control studies on colonoscopy screening showing over 50% decrease in incidence and mortality. IncidenceMortality Winawer et al NEJM %, 88% and 90% Müller AD et al Ann Int Med % Citarda F et al. Gut % Kahi CJ et alClin Gastroenterol et Hepatol %65% Brenner H et al. Ann Int Med %

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 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 screening Increasing ! 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.