Everyone needs a colonoscopy at 50 for colorectal cancer prevention, but what if…they simply refuse? They can’t afford it due to insurance issues? We seem to have forgotten that the updated ACG guidelines of 2009 for first time recommend use of annual stool FIT testing as “the preferred cancer detection test” if colonoscopy was not available or refused. How does FIT differ from our venerable stool guaiac testing? And is it finally time to discard gFOBT (AKA guaiac testing) as an insensitive and nonspecific diagnostic tool? Join our conversation and see how FIT testing fits our current screening guidelines, your patients’ financial limitations, and your excellent medical care.

1. Patricia L. Raymond MD FACG
Assistant Professor of Clinical Internal Medicine,
Eastern Virginia Medical School
what their stool can tell you:
How FIT (iFOBT) Fits
Your Colorectal Cancer Algorithm

2. Sponsored by an educational grant from Hemosure Inc.

4. We will cover:
… and perhaps change the tools you use
to detect blood in stool & colorectal cancer.
Screening
verses
detection
gFOBT,
iFOBT,
& the future
iFOBT
compliance
& outcomes

5. On the road to poopville

6. -rationale for screening for colorectal cancer
-the polyp-cancer sequence
-American College of Gastroenterology
2008 guidelines
-screening (colonoscopy)
-detection (FIT test)
-American Cancer Society 2012 guidelines

7. We do a poor job preventing colorectal cancer.
142,820 dx in 2013
American Cancer Society estimates

8. Colon Cancer
Statistics
Second leading cause of cancer deaths in the US
142,820 diagnosed, 50,830 deaths estimated for
2013
Early detection = 5 year survival
>90% if local stage
69% if to regional lymph nodes
20% if to distant organs
We don’t detect it early enough
39% local
37% regional
20% distant organs
6% of average risk Americans
will get colon cancer
ACS 2012 Cancer Facts and Figures, Colorectal Cancer Facts & Figures 2011-2013
Image from http://www.danielwagner.com/how-the-guru-send-me-traffic/

9. Polyp-Cancer Sequence
8-12 years
estimated for
polyp to
become cancer
Already a cancer:
Stage 0 Carcinoma in situ
Stage 1 Mucosal
Stage 2 To muscularis
Stage 3 To lymph nodes
Stage 4 To distant organs

10. Stage= Survival
Early detection = 5 year survival
>90% if local stage
69% if to regional lymph nodes
20% if to distant organs
We don’t detect it early enough
39% local
37% regional
20% distant organs

11. ACG 2008 guidelines – it’s been five years, people!
Changes in 2008 guidelines from the 2000 ACG
recommendations for screening
1. Screening tests are divided into cancer prevention
and cancer detection tests. Cancer prevention tests are
preferred over detection tests.
2. Screening is recommended in African Americans
beginning at age 45 years.
3. CT colonography every 5 years replaces double
contrast barium enema as the radiographic screening
alternative, when patients decline colonoscopy.
4. FIT replaces older guaiac-based fecal occult blood
testing. FIT is the preferred cancer detection test.
5. Annual Hemoccult Sensa and fecal DNA testing every
3 years are alternative cancer detection tests.
6. A family history of only small tubular adenomas in
first-degree relatives is not considered to increase the
risk of CRC.
7. Individuals with a single first-degree relative with CRC
or advanced adenomas diagnosed at age ≥60 years can
be screened like average-risk persons.

12. ACG 2008 : Preferred CRC screening recommendations
• Cancer prevention tests should be
offered first. The preferred CRC
prevention test is colonoscopy every
10 years, beginning at
age 50. (Grade 1 B)
• Screening should begin at age 45
years in African Americans
(Grade 2 C)
• Cancer detection test should be
offered to patients who decline
colonoscopy or another cancer
prevention test. The preferred
cancer detection test is annual
FIT for blood (Grade 1 B)

13. Time to discard stool guaiac?
“ ACG supports the joint guideline recommendation that
older guaiac-based fecal occult blood testing be
abandoned as a method for CRC screening.”

14. I’ve got job security. Detection verses prevention.
FIT for those who
refuse colonoscopy.

15. ACS guidelines on colorectal cancer screening & surveillance
Starting at age 50 years, men and women should
undergo one of the following screening tests (average
risk):
US Pharmacist. 2012;37(12):22-26.
Colorectal Cancer Screening Guidelines Update M Steinberg.
• Flexible sigmoidoscopy every 5 y
• Colonoscopy every 10 y
• Double-contrast barium enema every 5 y
• CT colonography every 5 y
• FOBT annually (take-home, multiple-sample method)
• FIT annually (take-home, multiple-sample method)

16. American Cancer Society guidelines
Method DescriptionNotes
Flexible sigmoidoscopy
Flexible, lighted, tubelike video camera
inserted into rectum allows visualization of
entire rectum, but less than half of colon
Requires bowel preparation
Colonoscopy
Flexible, lighted, tubelike video camera
inserted into rectum allows visualization of
entire rectum and colon; has ability to
remove any identified polyps
Requires bowel preparation; use of sedation
requires patient to rely on another person to
drive him/her home after the procedure
Double-contrast barium enema
Barium sulfate suspension is injected with air
into rectum via flexible tube; x-ray images are
taken
Requires bowel preparation; colonoscopy
may be performed to evaluate/remove any
suspicious polyps
CT colonography
Patient lies within scanning machine, which
rotates around him/her taking cross-sectional
images that enable 2-or 3-dimensional
visualization of colon and rectum
Requires bowel preparation; may require
drinkable contrast solution, as well as
insertion of air into colon to improve
visualization; colonoscopy may be performed
to evaluate/remove any suspicious polyps
FOBT
Patient applies stool sample (usually 3
consecutive bowel movements) to test-kit
cards and returns/mails completed kit to
medical office/laboratory
Requires colonoscopy for positive test to
determine cause of bleeding; NSAIDs, aspirin,
vitamin C (>250 mg/day), or red meat ≤3 days
before testing interacts with accuracy; may
not detect nonbleeding tumors
FIT or iFOBT
Patient applies stool sample (usually 2–3
consecutive bowel movements) to test-kit
cards and returns/mails completed kit to
medical office/laboratory
Requires colonoscopy for positive test to
determine cause of bleeding; no dietary
limitations; may not detect nonbleeding
tumors
US Pharmacist. 2012;37(12):22-26.
Colorectal Cancer Screening Guidelines Update M Steinberg.

17. ACS guidelines on increased CRC risk
US Pharmacist. 2012;37(12):22-26.
Colorectal Cancer Screening Guidelines Update M Steinberg.
Increased Risk (due to FH of colorectal cancer)
Risk Category Age/Time to Begin Recommended Test
Colorectal cancer or
adenomatous polyps in any
1st-degree relative <60 y or
≥2 1st-degree relatives at
any age
Age 40 y, or 10 y before
youngest immediate-family
case
Colonoscopy every 5 y
Colorectal cancer or
adenomatous polyps in any
1st-degree relative ≥60 y or
≥2 2nd-degree relatives at
any age
Age 40 y Colonoscopy every 10 y

18. ACS guidelines on high CRC risk
US Pharmacist. 2012;37(12):22-26.
Colorectal Cancer Screening Guidelines Update M Steinberg.
Risk Category Age to Begin Recommended Test(s)
FAP diagnosed by genetic
testing, or suspected
without genetic testing
Age 10–12 y
Yearly flexible
sigmoidoscopy; genetic
testing
HNPCC or FH of condition
Age 20–25 y or 10 y before
youngest immediate-family
case
Colonoscopy every 1–2 y;
genetic testing
Inflammatory bowel
disease
Unclear, but cancer risk begins ≤8 y after Colonoscopy
with biopsy pancolitis onset or 12–15 y after LC onset
every 1–2 y

19. It’s working!

22. More uninsured, so they get stool testing
at least, right?
http://www.examiner.com/article/free-health-care-101-where-to-find-chicago-s-low-and-no-cost-health-care

25. -causes of false-positives with guaiac-based
FOBT(gFOBT)
- how immunochemical FOBT (iFOBT
or FIT) works
-the future of & development of fecal
DNA testing

26. Albert Einstein
Everything should be made as
simple as possible, but not simpler.

27. Standard Guaiac testing
Peroxidase reaction with hemoglobin
turns guaiac impregnated paper blue
Hemoccult sensa is more sensitive
than Hemoccult, Hemoccult-II or
Hemoccult-R
• hydrogen peroxide is dripped onto the
guaiac paper
• oxidizes the alpha-guaiaconic acid to a
blue colored quinone
• occurs very slowly when no blood (& no
peroxidases or catalases from vegetables)
are present
• Heme catalyzes this reaction, giving a
result in about two seconds
• positive test result is one where there is a
quick and intense blue color change of the
film.
Your Meemaw’s gFOBT
Image from http://digital-photography-school.com/forum/how-i-took/59938-chuck-norris-eyedrops.html
Kratochvil JF, et al. (1971). "Isolation and characterization of alpha-guaiaconic acid and the nature of guiacum blue". Phytochem 10: 2529.

28. Dietary restrictions– who actually follows them?
Restrictive diet advised
• high fiber diet x 2 days
• no red meat
• no vitamin C or citrus fruits
• false negatives due to anti-oxidant
properties inhibiting
the color reaction
• no gastric irritant medications
• includes iron
• no peroxidase containing
vegetables (cucumber, cauliflower,
horseradish)
• Reduced compliance with
screening
Biennial (every 2 years) screening
with non-rehydrated specimens
Beg M, et al. (2002). "Occult Gastrointestinal Bleeding: Detection, Interpretation, and Evaluation" JIACM 3 (2): 153–8.

29. Food peroxidases & guaiac testing
In vivo study, N = 61
Peroxidase challenge diet for three days
with 750 g of raw peroxidase-rich fruits
and vegetables daily
160–180 g of broccoli
160–180 g of cauliflower
40–50 g of red radish
110–120 g of turnip
250–280 g of cantaloupe
“… ingested plant peroxidases are capable
of surviving transit through the gut and
that, in the feces, they can cause positive
guaiac-based FOBT reactions… the ability
of plant peroxidases to cause false-positive
reactions decreases rapidly as the
time between fecal smearing and
development increases.”
Clinical Chemistry January 1999 vol. 45 no. 1 123-126. Interference of Plant Peroxidases with Guaiac-based Fecal Occult Blood Tests Is Avoidable

30. If it is human blood, where from?
• Mouth and dental
• Esophagus
• Stomach
• Small intestine
• Colon
• Anal
Image from http://www.uofmmedicalcenter.org/healthlibrary/Article/40233 and
http://1.bp.blogspot.com/-Nxq4Bx0WK3k/T1zdJcnEh0I/AAAAAAAABUg/WArnSc1PgCg/s1600/Funny+joke+picture+on+Apple+iPhone+Ambulance+bleeding+help+humor+image.jpg

31. CRC mortality reduced by 33% at 13
years (annual gFOBT)and 21 % at 18
years (biennial gFOBT)
2% Guaiac + patients had cancer =
50 colonoscopies to detect 1 cancer
• Single FOBT sensitivity for CRC 30%
• Program of repeated testing
sensitivity 80-92%
• High false positive rate
• ? Chance detection of cancers
verses specific effect of gFOBT
• Does not detect polyps which do
not bleed, many false positive
results
More on gFOBT
Image from http://www.sciencemuseum.org.uk/hommedia.ashx?id=91853&size=Inline
Mandel JS, Church TR, Ederer F, Bond JH. Colorectal cancer mortality: effectiveness of biennial screening for fecal occult blood. J Natl Cancer Inst 1999; 91:434.
Allison JE, Sakoda LC, Levin TR, et al. Screening for colorectal neoplasms with new fecal occult blood tests: update on performance characteristics. J Natl Cancer Inst 2007; 99:1462.
Lang CA, Ransohoff DF. Fecal occult blood screening for colorectal cancer. Is mortality reduced by chance selection for screening colonoscopy? JAMA 1994; 271:1011.
Ederer F, Church TR, Mandel JS. Fecal occult blood screening in the Minnesota study: role of chance detection of lesions. J Natl Cancer Inst 1997; 89:1423.

32. Modern stool testing today: iFOBT (FIT)
More specific than guaiac testing
Respond only to human globin
• No false + for UGI bleed (globin
digested in transit)
• No false + for foods with
peroxidase activity
• Sensitivity does degrade in mailing
delay (degradation of hemoglobin)
• >5 days post sample verses no
delay with decrease in
adenoma detection (OR 0.6)
Qualitative and quantitative
testing available, with
adjustment of cut-off
Image from http://ncmuseumofhistory.org/exhibits/healthandhealing/topic/36/, http://dsc.discovery.com/tv-shows/curiosity/topics/modern-medicine-pictures.htm
van Rossum LG, van Rijn AF, van Oijen MG, et al. False negative fecal occult blood tests due to delayed sample return in colorectal cancer screening. Int J Cancer 2009; 125:746.

33. iFOBT (FIT) major advantages over traditional gFOBT
No diet or medication restrictions
Increased specificity with high
sensitivity
Specific to lower GI bleeding
-improved compliance (10-12%)
-DOUBLE detection advanced
lesions with little loss of PPV
Better patient return rate
Fewer false-positives for CRC
Ideal CRC screening product
Fewer false positives and needless colonoscopies

34. Using stool guaiac (gFOBT) is like using
Laennec’s stethoscope (1819)…
Image from http://www.homeopathyworldcommunity.com/forum/topics/rene-theophile-hyacinthe

35. Future fecal DNA testing (sDNA)
• CRC sheds DNA, mutations may be
tested
• Commercially available sDNA test off
market 2012, new panels under
development
• False negatives (unidentified
genetic abnormality), false + (upper
GI malignancy or premalignant
genetic abnormalities elsewhere in
GI tract)
Cost analysis 2010 pricing
• $350 per test
• sDNA every 3-5 years more costly
than other screening per year of
life saved.
• Could be cost effective at $40-60
Image from http://inside-the-brain.com/tag/future-of-medicine/
Imperiale TF, Ransohoff DF, Itzkowitz SH, et al. Fecal DNA versus fecal occult blood for colorectal-cancer screening in an average-risk population. N Engl J Med 2004; 351:2704.

37. -logistics of iFOBT (FIT)
testing
-compliance
-outcomes in population-based
prevention studies
How does this work?

38. How FIT testing is done

39. How FIT testing is done: poking the poop

40. In your office

41. Positive: Occult blood is detected in the
stool sample. Please consult a doctor
Negative: No occult blood is detected in the
stool sample.
Invalid: This may be due to
inadequate/excessive sample
being collected or delay in sample
transportation to the clinic.
In your office

42. Compliance with FIT
• No diet change
• No multiple samples
• No chasing stool in toilet with
popsicle stick
Now you can make fun
craft projects!
Image from http://www.mycafelove.com/2012/01/funny-face-made-from-vegetables-funny.html

43. Sealed with a iFOBT
Belgium 2009, N=19,542
Random mailings verses GP advice
42.1% overall participation (8229 fecal samples)
– 52.3% mail, 27.7% GP (p<0.001)
– 26.5% mail, 16.6% GP prior to
reminder letter and other
invitation strategy
Odds of participation almost 3 x
higher (OR= 2.96) for people invited
by mail than invited by their
physician

44. Sealed with a iFOBT (2)
• Women > Men (OR 1.22, p<0.001)
• Residential (OR=1.98) and rural
(OR=2.90) > urban
– 8229 sent sample
– 435 of 8229 (5.3%) positive iFOBT
– CRC in 18/317 scoped (5.7%)
Compliance for follow up colonoscopy
72.9%, did not differ in mail verses GP
groups
Van Roosbroek S, Hoeck S, Van Hal G. Population-based screening for colorectal cancer using an
immunochemical faecal occult blood test: a comparison of two invitation strategies. Cancer Epidemiol.
2012 Oct; 36(5):e317-24.

45. Population based studies
Belgium
Mail compliance vs. GP
Brazil
Population screening
Netherlands
Higher participation rate &
improved detection verses gFOBT
France
Better than gFOBT with lesions
that bleed less
Germany
Enhanced detection
despite/due to low dose aspirin use
FIT around the globe
(in developed
countries)

46. IMMUNOLOGICAL FECAL OCCULT BLOOD
TEST ON THE SCREENING FOR
COLORECTAL CANCER IN A BRAZILIAN
TOWN – PRELIMINARY RESULTS
Angelita HABR-GAMA, M.D.; Rodrigo Oliva PEREZ, M.D., Igor PROSCURSHIM,
M.D., Guilherme Pagin SÃO JULIÃO, M.D., Mauro PICOLO, M.D.,
Joaquim GAMA-RODRIGUES, M.D.,
Project carried out in
Santa Cruz das Palmeiras
municipality, São Paulo
state, Brazil, sponsored by
ABRAPRECI – Brazilian
Association for Colorectal
Cancer Prevention
4,567 FIT tests
54.8% of the local
population over 40 years
• 905 (19.8%) were not
returned
• 22 (0.5%) could not be
analyzed.
• 3,640 tests, 43.7% of
the target population,
were analyzed
• Results were positive
in 390 (10.7%) exams

47. FIT Brazilians
FIT positive in 390 (10.7%)
exams
Out of the 245 patients with
positive result and referred to
colonoscopy, 33 (13.5%)
refused to undergo the exam.
The results of the 212
performed colonoscopies
were:
• 53 patients with
diverticular disease,
• 59 with polyps
• 9 with adenocarcinoma
• 91 normal.
32% yield of polyps and cancer
Out of the patients with
adenocarcinoma, three were
treated endoscopically since
lesions were small and
detected at an early stage.

48. Participation rate FIT > gFOBT
In a randomized trial in
the Netherlands
comparing Hemoccult
II (guaiac-based), a
quantitative fecal
immunochemical test
(FIT), and flexible
sigmoidoscopy for
screening, the
participation rate was
higher for the FIT
compared to the
guaiac test (61.5%
versus 49.5%)
Screening for colorectal cancer: randomised trial comparing guaiac-based and immunochemical faecal occult blood testing and flexible sigmoidoscopy.
Hol L, van Leerdam ME, van Ballegooijen M, van Vuuren AJ, van Dekken H, Reijerink JC, van der Togt AC, Habbema JD, Kuipers EJ
Gut. 2010;59(1):62. Image from http://www.123rf.com/photo_6011092_windmill-with-tulip-field-near-schermerhorn-netherlands.html

49. gFOBT + 2.8%
FIT + 4.8%
FFS + 10.2%.
Detection of
advanced neoplasia
was significantly
higher in the FIT
(2.4%; OR, 2.0; CI,
1.3 to 3.1) and the FS
arm (8.0%; OR, 7.0;
CI, 4.6 to 10.7) than
the gFOBT arm
(1.1%)
Screening for colorectal cancer: randomised trial comparing guaiac-based and immunochemical faecal occult blood testing and flexible sigmoidoscopy.
Hol L, van Leerdam ME, van Ballegooijen M, van Vuuren AJ, van Dekken H, Reijerink JC, van der Togt AC, Habbema JD, Kuipers EJ
Gut. 2010;59(1):62. Image from http://www.123rf.com/photo_6011092_windmill-with-tulip-field-near-schermerhorn-netherlands.html

50. FIT: More sensitive with less bleeding lesions
N=20 322 , tested with gFOBT and
FIT
At least 1 positive test in 1615,
colonoscopy results were
available for 1277
43 invasive cancers and 270 high-risk
adenomas were detected.
The gain in sensitivity associated
with the I-FOBT was calculated
using the ratio of sensitivities
(RSN) according to type and
location of lesions, and amount of
bleeding.
The gain in sensitivity by using I-FOBT
increased from invasive
cancers (RSN=1.48 (1.16-4.59)) to
high-risk adenomas (RSN=3.32
(2.70-4.07)), and was inversely
related to the amount of
bleeding.
Comparison of a guaiac and an immunochemical faecal occult blood test for the detection of colonic lesions according to lesion type and location.
Guittet L, Bouvier V, Mariotte N, Vallee JP, Levillain R, Tichet J, Launoy G
Br J Cancer. 2009;100(8):1230.

51. “…use of low-dose aspirin compared with no
aspirin was associated with a markedly higher
sensitivity for detecting advanced colorectal
neoplasms, with only a slightly lower specificity.”
2 different FIT tests in
1979 patients (mean
age, 62.1 years):
• 233 regular users of
low-dose aspirin
• 1746 who never
used low-dose
aspirin
• Advanced
neoplasms were
found in 24 users
(10.3%) and 181
nonusers (10.4%) of
low-dose aspirin
Low-dose aspirin use and performance of immunochemical fecal occult blood tests.
Brenner H, Tao S, Haug JAMA. 2010;304(22):2513.

52. INVITING TRAGEDY

53. Remember: + FIT needs colonoscopy

54. ? Questions…
Please ask!
Patricia Raymond MD FACG

55. Learn more: Resources
» Guidelines for Colorectal Cancer Screening 2008 -
American College of Gastroenterology
» www.s3.gi.org/media/ACG2009CRCGuideline.pdf
» Review slides wherever you are
» Slideshare.net/PatriciaRaymond

56. Learn more: Selected Resources
» ACG & Cancer Detection Testing with FIT
Nakajima M , Saito H , Soma Y et al. Prevention of advanced colorectal
cancer by screening using the immunochemical faecal occult blood test: a
case-control study . Br J Cancer 2003 ; 89 : 23 – 8 .
Lee KJ , Inoue M , O tani T et al. C olorectal cancer screening using fecal
occult blood test and subsequent risk of colorectal cancer: a prospective
cohort study in Japan . Cancer Detect Prev 2007 ; 31 : 3 – 11 .
Zappa M , Csatiglione G , rGazzini G et al. E7 ect of faecal occult blood
testing on colorectal mortality: results of a population-based case-control
study in the district of Florence, Italy . Int J Cancer 1997 ; 73 : 208 – 10 .
van Rossum LG , van Rijn AF , Laheij RJ et al. Random comparison of guaiac
and immunochemical fecal occult blood tests for colorectal cancer in a
screening population . Gastroenterology 2008 ; 135 : 82 – 90 .
Hol L , van Leerdam ME , van Ballegooijen M et al. Attendance to
screening for colorectal cancer in the Netherlands; randomized controlled
trial comparing two different forms of faecal occult blood tests and
sigmoidoscopy . Gastroenterology 2008 ; 134 : A87 .

57. Patricia L. Raymond MD FACG
Assistant Professor of Clinical Internal Medicine,
Eastern Virginia Medical School
what their stool can tell you:
How FIT (iFOBT) Fits
Your Colorectal Cancer Algorithm

58. Just what is their stool telling you?