COLORECTAL CANCER SCREENING
Alan N. Barkun
Professor, Division of Gastroenterology
Chairholder of the DG Kinnear Chair in Gastroenterology,
Chief Quality Officer, Division of Gastroenterology,
McGill University and the McGill University Health Centre
Chair of the Clinical Standards and of the Evaluation
of Endoscopic Competence Committees,
Quebec Colorectal Cancer Screening Program
Objectives
At the end of the presentation, participants
should
 Understand the different screening options for
colorectal cancer available to patients
 have become familiar with the test
performance characteristics of the different
screening approaches
 be able to explain to patients their benefits
and disadvantages
Why is CRC uniquely suited for screening?
 CRC is common + highly lethal if caught late
 CRC has a long asymptomatic pre-clinical phase
 Accurate screening tests widely available
 Early detection of CRC & polyps improves survival
 The benefits outweigh the harms/costs
Epidemiology

Colorectal cancer is a leading cause of death in the
Western World

In Canada, it is the third most common cancer in both sexes
In 2010
New Cases
Deaths
Quebec
5900
2500
CUMULATIVE LIFETIME RISK IN
(3rd)
(2nd)
USA/Canada: 1:21/1:22 and 1:49/1:54
Colorectal Cancer – biology
CDHF.ca
• If diagnosed early 95% will survive; presently
only 35% of cases diagnosed at this stage
• 60% will die if cancer
spreads to lymph nodes
• 95% will die if cancer
spreads to distant organs
CRC a perfect disease
paradigm for screening
IT IS PREVENTABLE
Polyp-cancer sequence 8-12 yrs (80%)
2011 Digestive Health Summit for Health Care Professionals
The most common risk factor: AGE
CDHF.ca
Canadian Cancer
Statistics 2011
2011 Digestive Health Summit for Health Care Professionals
Screening for CRC - so far:

CRC is amenable to screening

Age is the main risk factor for average risk
screening

Need to start screening at age 50

Should screen every 10 years (if good test
available)
FOBT- Meta-analysis of these trials
4
trials totaling almost 450,000 patients
16%
risk reduction in CRC related mortality (23%
in compliant patients)
RR=0.84;
NN
CI: 0.77-0.93
to screen to prevent 1 death: 1173
Fecal Immunochemical Testing

The FIT detects more specifically human hemoglobin that
arises from the lower GI tract

Easier to use, more quantifiable; high throughput
technology

4 trials performed in a populational setting; only first-round
screening and no cancer registry follow-up as of yet (Italy,
Netherlands); additional trial out of China – very preliminary
data

FIT outperforms gFOBT with a lower level of reported
discomfort and overall burden
Fecal Immunochemical Testing vs Guaiac

FIT Positive Rate of 3.5 to 8.1% (decreases with increasing
threshold value 50-200 ng/ml) vs 2.8% Guaiac

More patients referred to colonoscopy at every threshold
with FIT vs Guaiac

Detection rates greater for FIT 2-3.1% vs Guaiac 1.2% for
significant lesions

PPV greater for FIT: 62% vs 45% (FIT=75ng/ml)

Inferior specificity for FIT: 92.9 vs 97.6%
vanRoon, 2011
FIT performance

Participants (50-75 years) in an invitational primary
colonoscopy screening program were asked to complete
one sample FIT before colonoscopy

A total of 1,256 participants underwent a FIT and screening
colonoscopy

The positive and negative predictive values for FIT50 were
6% (95% CI: 3-12) and almost 100% (95% CI: 99-100) for
CRC, and 37% (95% CI: 29-46) and 93% (95% CI: 92-95)
for advanced neoplasia
de Wijkerslooth , AJG, 2012

N = 19 studies

Pooled sensitivity, specificity, (+) and (-) likelihood ratio of
FITs for CRC were 0.79 (95% CI, 0.69 to 0.86), 0.94 (CI, 0.92
to 0.95), 13.10 (CI, 10.49 to 16.35), 0.23 (CI, 0.15 to 0.33);
diagnostic accuracy of 95% (CI, 93% to 97%)

Lower thresholds yielded highest sensitivities (for example,
0.89 [CI, 0.80 to 0.95] at a cutoff value less than 20 mcg/g vs.
0.70 [CI, 0.55 to 0.81] at cutoff values of 20 to 50 mcg/g) but
with a corresponding decrease in specificity.

A single-sample FIT had similar sensitivity and specificity as
several samples, independent of FIT brand
Lee, AIM, 2014
FLEXIBLE SIGMOIDOSCOPY
www.edoctor.co.in
image.healthhaven.
com
Flex sig
metaanalysis
Littlejohn, Br J Surg, 2012
COLONOSCOPY
www.flickr.com
www.tcnj.edu
db2.photoresearchers.com
image.healthhaven.com
Long-Term Colorectal-Cancer Incidence and
Mortality after Lower Endoscopy
Association of lower endoscopy (1998-2008) with
colorectal-cancer incidence (2010) and mortality (2012)
among participants in the Nurses’ Health Study and the
Health Professionals Follow-up Study
88,902 participants over 22 years, 1815 incident
colorectal cancers and 474 deaths from colorectal cancer
Nishihara, NEJM, 2013
Long-Term Colorectal-Cancer Incidence and Mortality
after Lower Endoscopy
Nishihara, NEJM, 2013
Adenoma Detection Rate (ADR)
and Risk of Colorectal Cancer and Death
 314,872 colonoscopies performed by 136 GIs w ADRs:
Jan 1998 - December 2010; f-u of at least 6 mos
 712 interval colorectal adenocarcinomas, including 255
advanced-stage cancers, and 147 deaths from interval
colorectal cancer
Corley, NEJM, 2014
ADR and CRC
Each 1.0% increase
in ADR
associated with 3%
decrease in cancer
risk
(HR=0.97;
95%CI 0.96 to 0.98)
Corley, NEJM, 2014
Colonoscopy vs FIT screening RCT
Higher adherence in FIT than colonoscopy (34.2% vs. 24.6%, P<0.001)
First of 5 RCTs of colonoscopy, 4 population-based
Quintero, NEJM, 2012
CT COLOGRAPHY (virtual colonoscopy)
www.agfahealthcare.com
www.ultimatehealthguide.com
lsgimaging.com
www.ebook3000.com
Average sensitivity and specificity of
screening methods
Systematic review included:
•
•
•
•
20 studies for colonoscopy
12 studies for sigmoidoscopy
26 studies for Barium enema
62 studies for CT colonography
Allameh et al. Iran J Cancer Prev. 2011
Virtual colonoscopy
Not recommended for screening:
- lack of data
- risk of irradiation
- downstream implications of incidentalomas
- unfavorable cost-effectiveness
Alternative diagnostic strategies:
Fecal DNA
Noninvasive, multitarget stool DNA test (KRAS mutations, aberrant
NDRG4 and BMP3 methylation, and β-actin, plus a hemoglobin
immunoassay) vs FIT (100ng/ml) in persons at average risk for CRC
n=9989, with 65 (0.7%) CRC and 757 (7.6%) advanced
precancerous lesions (advanced adenomas or sessile serrated
polyps measuring ≥1 cm in the greatest dimension) on colonoscopy
Sensitivity for CRC: 92.3% DNA testing vs 73.8% FIT (P = 0.002)
Imperiale, NEJM, 2014
Alternative diagnostic strategies:
Fecal DNA
Sensitivity for advanced precancerous lesions 42.4% DNA
testing vs 23.8% FIT (P<0.001)
Polyps with high-grade dysplasia was 69.2% with DNA
testing vs 46.2% with FIT (P = 0.004)
Serrated sessile polyps>1cm: 42.4% vs 5.1%, (P<0.001)
Specificities 86.6% and 94.9%, respectively, among
participants with nonadvanced or negative findings
(P<0.001) and 89.8% and 96.4%, respectively, among
those with negative results on colonoscopy (P<0.001)
NN screen to detect one cancer: 154 with colonoscopy,
166 with DNA testing, and 208 with FIT
Imperiale, NEJM, 2014
COLONIC WIRELESS CAPSULE
ENDOSCOPY
mygeorgetownmd.org
www.endoatlas.com
www.endoatlas.com
www.vcharkarn.com
www.umm.edu
www.bgapc.com
The colonic capsule
Spada, CGH, 2010
The role of patient preference?

Systematic review of colonoscopy vs CTC patient
preference showed that most included studies reported
preference for CTC

Screening patients preferred CTC while diagnostic patients
showed no preference

With comprehensive information, colonoscopy and CTC
were seen as having different advantages and
disadvantages, yielding no clear preferences between
the two
Lin, J Gen Int Med, 2012; Ghanouni, Patient Educ Counsel, 2012
AN OVERALL
ACCURACY OF
76%!
Altomare, Br J Surg, 2013
CONCLUSION

Any CRC screening better than none

Many efficacious detection techniques for CRC

Limitations:





Feasibility (Flex sig, colonoscopy, low FIT thresholds)
Morbidity (quality is key for efficacy and safety)
Technology (?CT colography, colonic WCE, ?Volatile organic
compounds detection)
Costs (CT colography, fecal DNA)
Most population-based programs remain FOBT-based
Colonoscopy (and CT colography) remain very popular for
opportunistic screening

CONCLUSION

Need for additional head-to-head testing with adequate
follow-up

Consider “enhanced” detection methods

A quality colonoscopy is key!

?Down the road: A menu of available testing
alternatives/combination thereof tailored to the patients
risks and preference profiles?