Familial Adenomatous
Polyposis
Recommendations
High Risk Asymptomatic – Family Hx FAP
High Risk Asymptomatic – Family Hx HNPCC
Tests for Detection of Colorectal Neoplasm
Flexible Sigmoidoscopy
and FOBT
This guideline provides recommendations for the
detection of colorectal cancer and adenomas in asymptomatic patients. These recommendations
are intended to rationalize screening for various patient
groups. They do not apply to patients with previous colorectal cancer, anemia,
or bowel related symptoms.
Screening should not be offered to an individual where the findings would not alter the patient's management due to age or co-morbidity.
Recommendations for asymptomatic patients following
curative resection of colorectal cancer are
specified in the guideline, Follow-up of Patients
after Curative Resection of Colorectal Cancer.
Individuals can be classified as having average,
moderate and high risk for colorectal cancer (CRC). Approximately
75 per cent of all colorectal cancer occurs in patients of average risk with no
family
history.' At the present time there is no evidence
that people with other sporadic cancers (e.g. breast) are at increased risk of developing CRC.
High risk patients:
Previous colorectal cancer
Family history of:
familial adenomatous polyposis (FAP) - see below
hereditary nonpolyposis colon cancer syndrome (HNPCC) - see below
Moderate risk patients:
Previous adenomas
Longstanding inflammatory bowel disease2
CRC in first degree relatives (see Recommendation 3)
Average risk patients:
Meet none of the above criteria
For complete description of tests for the detection of
colorectal neoplasms, see pages Tests subsection
FAP is a rare autosomal dominant condition in which
affected individuals develop countless colorectal adenomas. Polyp formation begins
between puberty and age 40. These polyps will inevitably progress to CRC if
therapeutic intervention is not undertaken. Genetic counselling and testing
should be offered to all 1st degree relatives*. Currently genetic testing for FAP is not
covered by MSP in British Columbia. Genetic counselling and testing for FAP can be
obtained by referral to the Hereditary Cancer Program at the BC Cancer Agency.
In Vancouver call: 604 877-6000 ext. 2325
·
Other areas call toll free: 1 800 663-3333 ext.
2325.
Family members with negative genetic tests should be
treated as average-risk individuals, see Recommendation
2.
·
In the absence of clearly negative genetic test
results, see Recommendation 4.
Note: *1st degree relatives include:
parents, brothers, sisters and their children. 2nd degree relatives
include: grandparents and grandchildren.
HNPCC is a rare familial condition defined by the Amsterdam Criteria
IIt3,4:
a) Three or more family members with CRC, or any Lynch Syndrome
malignancy (see below), one of
whom must be a first degree relative of the other
two.
b) At least two generations must be affected by CRC
or Lynch Syndrome
malignancy.
c) At least one CRC must be diagnosed before age 50
years.
Two subtypes of HNPCC have been identified: one with
CRC only (Lynch Syndrome I), the other is associated with
cancer of the endometrium, small bowel, ureter or renal pelvis (Lynch Syndrome II). For patients
with small families or incomplete family histories, some leeway in the above
criteria may be applied in determining the patient's risk
classification for CRC.
Individuals with a family history of HNPCC should be
screened by colonoscopy beginning ten years less than the age at presentation
of the youngest family member who had colorectal cancer;5' 6 or
at age 25. Colonoscopy should be performed every 2
years until age 40, then annually thereafter. 3,'
It is important to note that HNPCC adenomas progress
rapidly to carcinoma and that many HNPCC neoplasms are in the proximal
colon. When HNPCC is suspected in a family, genetic testing and counselling
should be offered. Currently genetic testing for HNPCC is not covered by MSP in
British Columbia. Genetic counselling and testing for HNPCC can be obtained by
referral to the Hereditary
Cancer Program at the BC
Cancer Agency
Hereditary Cancer Program:
In Vancouver call: 604 877-6000 ext. 2325
Other areas call toll free: 1 800 663-3333 ext.
2325.
tThis list has been expanded
in the Bethesda Criteria - see reference.
RECOMMENDATION
1: All
patients 50 years of age and over
Annual digital rectal examination (DRE).
RECOMMENDATION 2: Average Risk Asymptomatic Patients
No known risk factors
a) Fecal occult blood test (FOBT) - yearly,
between age 50 and 75 (recommended)
b) Flexible Sigmoidoscopy - every 5
years, between age 50 and 75 (optional, in addition to FOBT)
Colorectal cancer in 2nd degree relatives of any age
a) Colonoscopy -every 10 years between age 50 and
75, or
b) Double contrast barium enema (DCBE) and flexible sigmoidoscopy - every 5 -10 years, between age 50 and 75.
Adenomatous polyp in a 1St degree relative younger
than age 60
a) Colonoscopy - every 10 years between age 50 and
75, or
b) DCBE and flexible sigmoidoscopy -every 5 -10
years, between age 50 and 75.
RECOMMENDATION 3: Moderate risk asymptomatic patients
Colorectal cancer in 1st degree relative, age 55 or
younger; or two or more 1st degree relatives of any age
·
Colonoscopy -every 5 years beginning at age 40 or 10
years before the age of presentation of the youngest case in the
family, whichever is lower.
Colorectal cancer in 1st degree relative over age 55
·
Colonoscopy -every 10 years beginning at age 40.
Personal history of polyp >1 cm, or multiple
colorectal adenomas of any size
·
Colonoscopy - 3 years after polypectomy
and every 5 years thereafter if recurrent adenomas are present; if no further adenomas then every 10
years thereafter.
Personal history of 1 or 2 colorectal adenomas <1
cm
·
Colonoscopy - 5 years after polypectomy and
every 5 years thereafter if recurrent adenomas are present; if
no further adenomas then every 10 years thereafter.
Inflammatory Bowel Disease involving entire colon
for over eight years or the left colon for over 15 years
·
Colonoscopy every 1-2 years in patients without
dysplasia.
RECOMMENDATION 4: High risk asymptomatic patients
– Family History of FAP
These patients should be referred to a specialist
for evaluation, ongoing monitoring, genetic counselling and testing.
Flexible sigmoidoscopy should start annually at age 12, then every 2 years from
age 25, then every three years from age 35, then as per the
guidelines for average-risk individuals starting at age 50 years.
RECOMMENDAITON 5: High
risk asymptomatic patients – Family History of HNPCC
These patients should be referred to a specialist
for evaluation, ongoing monitoring, genetic counselling and testing.
Colonoscopy every two years starting at age 25 or ten years before the age of
presentation of the youngest case of CRC in the family, and
annually after age 40.
1. Fecal Occult Blood Test (FOBT)
·
FOBT detects the presence of hemoglobin in
the stool and therefore is an indirect method of detection of neoplasia.
FOBT is pointless and unnecessary in patients who report frank blood in the
stool. FOBT is a sensitive test for hemoglobin from any source,
including dietary intake. Neoplasms in the colon bleed intermittently, therefore
the sensitivity of a single FOBT for the detection of neoplasia is low.8
|
Number of
positive FOBT cards |
Percent
pts* with advanced
neoplasia |
|
0 of 3 |
9% |
|
1 of 3 |
23% |
|
2 of 3 |
33% |
|
3 of 3 |
53% |
*Lieberman and Weiss, NEJM
2001;345:557
·
A strong association exists between the number of
positive test cards and the likelihood of advanced neoplasia. The standard
recommendation is to test separate stool samples from three days annually. A
single positive test warrants evaluation of the whole colon (see colonoscopy)9.
·
Sensitivity of FOBT has been shown to range from 12%
(any neoplasia) to 36% (high grade neoplasia). The positive predictive value
(probability that a person with a positive test has neoplasia) was 54% for any
neoplasia, and 40% for advanced neoplasia; the negative predictive value
(probability that a person with a negative test does not have
neoplasia) was 64% and 88% respectively.9
·
Despite its shortcomings, FOBT is suitable for
general population screening because it is widely available,
inexpensive and simple to use. Patient compliance is a problem with FOBT as
only about half of patients submit all three samples.10
Pro: non-invasive; inexpensive; widely
available
Con: low specificity
and sensitivity for neoplasia; poor patient
compliance
Flexible sigmoidoscopy examines the distal colon and
rectum and therefore misses the 40% of
cancers and polyps that are beyond its reach."
Biopsies and polypectomies can be performed during this procedure. The
bowel must be cleansed with an oral laxative or an enema for adequate visualisation.
The test takes approximately 5 to 10 minutes to perform.
Pro: greater specificity than
FOBT usually does not require sedation; biopsy for diagnosis permits
concomitant
biopsy
Con: limited examination of
the colon; discomfort; accuracy is dependent upon operator expertise and patient
preparation; rare bowel perforation (0.014%)10; may not be readily available; no advantage
over colonoscopy
3. Flexible
Sigmoidoscopy and FOBT
This combination has been used to offset the
limitations of FOBT and flexible sigmoidoscopy when used alone. Unfortunately this
combination fails to identify about 25% of patients with advanced neoplasia and about 50% of patients with advanced
neoplasia in the proximal colon.9
Pro: combined approach
has a higher
sensitivity than a non-combined approach; direct visualisation
of left
sided lesions
Con: fails to identify approximately
25% of patients with advanced neoplasia and about 50% of patients with advanced proximal neoplasia
Colonoscopy is currently the gold standard because
it allows for direct inspection of the entire colon, and it allows for biopsy and
polypectomy which are not possible with diagnostic imaging studies. Recent studies indicate that advanced neoplasia
is more uniformly distributed throughout the colon than was previously believed and therefore
justifies colonoscopy.12 Colonoscopy
takes approximately 15-30 minutes to perform. The bowel must be completely cleansed
with an oral laxative for adequate visualisation.
Colonoscopy usually requires sedation.
Colonoscopy is an expensive but effective test.8 Complications
can arise from the bowel preparation as
well as the procedure (including electrolyte disturbance, bowel perforation
(0.05%)13, bleeding
(0.19%).14
Pro: high sensitivity and specificity; allows for immediate biopsy and
polypectomy; examines entire colon
Con: requires sedation; time needed for preparation, procedure and recovery; risk of bleeding and perforation; accuracy of the colonoscopy depends on the
expertise of the endoscopist
A barium enema examination can be performed as
either a single contrast procedure or a double contrast procedure. Single
contrast barium enema outlines the colon with barium alone. Double contrast
barium enema (DCBE), also known as Air Contrast Barium Enema (ACBE), utilizes a
combination of air and barium resulting in better visualisation of
mucosal detail. Single contrast examinations are generally not
recommended because of low sensitivity.
DCBE enables total colonic imaging, but overall is
less accurate than colonoscopy.15 DCBE has similar
detection rates for clinically
significant lesions (greater than 1 cm in diameter). For lesions less than 1 cm
in diameter, DCBE is less sensitive than colonoscopy, especially in the rectum.
DCBE is highly dependent on several
factors, particularly meticulous bowel preparation. DCBE takes approximately 30-45
minutes to perform.
Pro: widely available
Con: less accurate than colonoscopy; does not permit concomitant biopsy or polyp removal
CTC (also known as Virtual Colonoscopy) is a total
colonic imaging tool utilizing a specialised multislice CT
scanner. It is a relatively brief procedure that does require bowel preparation
and insufflation of carbon dioxide gas. 11 The
examination occurs during a single breath hold of 10 seconds or less.17
At the present time the role of this
technique is under study.
Pro: minimally invasive; low radiation exposure
Con: high cost procedure; lack of availability;
at the present time limited data regarding accuracy; does not permit concomitant biopsy or polyp removal
This test detects abnormal DNA in CRC cells shed in
the stool. This test shows promise but is not currently available.
Pro: highly specific (100%); cost disadvantage is counterbalanced by high specificity thereby precluding the need for follow-up colonoscopy which would have been needed by many
patients with
a false-positive FOBT
Con:
expensive; poor sensitivity (37%); not currently available
Colorectal cancer (CRC) ranks as the third most
common malignancy in Canada and the second most frequent cause of cancer death.18 The
incidence of CRC rises steadily after the age of 50. More than
700 people die each year from CRC in British
Columbia."
The majority of colon cancers arise in pre-existing
adenomas (the so-called 'adenoma-carcinoma sequence'). Generally adenomas
are polypoid lesions of the bowel mucosa. They may be readily identified
and removed during endoscopic examination. All adenomas have malignant
potential and the risk is proportional to the size; the risk
becomes significant with adenomas 1 cm or greater, and the risk
dramatically increases with adenomas greater than 2 cm in diameter. It has been
estimated that the time taken for a small adenoma to develop
into a carcinoma is rarely less than three years and in most cases
considerably longer. Removal of adenomas has been demonstrated to reduce colon cancer
mortality.2
Detection of neoplasms is facilitated by history,
physical examination, including digital rectal examination (DRE), fecal occult
blood testing (FOBT),
endoscopy and diagnostic imaging. The current debate among professional
organizations centres on the particular type of test to use, the appropriate age to begin
testing, and test frequency.20, 21
First degree relatives of CRC patients have an
increased risk for developing this disease. The risk increases
with the number of relatives affected and with younger age at diagnosis.
Rarely, families have a CRC syndrome such as familial adenomatous polyposis (FAP) or hereditary
nonpolyposis colon cancer (HNPCC). Patients with these syndromes
typically present in early adulthood. Patients with FAP develop
hundreds of colorectal adenomas; multi-focal cancer is inevitable unless
prophylactic therapy is provided. HNPCC patients have fewer adenomas, but the
malignant potential is higher than for sporadic adenomas.
Non-genetic factors that may increase the risk of
developing CRC include a high animal fat diet, physical inactivity, and
obesity.
Two major types of polyps are found in the large
bowel: adenomas and hyperplastic polyps. Hyperplastic polyps are considered to
have no malignant potential. Adenomas may be rounded polyps usually on a
stalk (tubular adenomas), broad based papillary growths (villous adenomas) or
coin shaped flat lesions with a central depression (flat adenomas); tubular
adenomas are the commonest type of adenoma. Most, but not all colon
cancers develop in pre-existing adenomas. The risk of an adenoma becoming
malignant is related to its histological type and size. The risk is greatest
for villous adenomas, flat adenomas and for adenomas of all
types greater than 2 cm in diameter. Generally it takes three
to five years for a small adenoma to develop into a malignancy. Recently, some
of the molecular abnormalities underlying the polyp-cancer
sequence have been discovered. The three to five year interval between growth
of a small adenoma and the development of invasive cancer permits cancer
prevention by endoscopic removal of this precursor lesion. Colon cancer and
polyps can occur in any area of the colon and rectum but 60 per cent are found
distal to the splenic flexure.
For patients who test positive for occult blood or whose sigmoidoscopy
reveals a neoplastic lesion (carcinoma or adenoma),
full colonoscopy is advised. Under exceptional circumstances, when colonoscopy
is not readily available or feasible, double-contrast barium enema plus
flexible sigmoidoscopy may be used as an alternative.15
Colon cancer screening represents an evolving field.
A multiplicity of guidelines exist. This guideline represents an amalgamation
of various published recommendations.22
1 Stoffel EM, Syngal S. Colon cancer
screening strategies. Curr Op Gastroenterol 2002;18:595-601.
2 Winawer S, Fletcher R, Rex D,
Bond J, Burt R, Ferrucci J, et al. Colorectal Cancer Screening and
Surveillance: Clinical Guidelines and Rationale - Update
Based on New Evidence. Gastroenterol 2003;124:544-60.
3 Cruz-Correa M, Giardiello FM.
Diagnosis and management of hereditary colon cancer. Gastroenterol Clin North Am 2002;31:537-49.
4 Raedle J, Trojan J, Brieger A,
Weber N, Schafer D, Plotz G, et al. Bethesda Guidelines: Relation to Microsatellite Instability and MLH1 Promoter Methylation in
Patients with Colorectal Cancer. Ann Intern Med2001;135:566-76.
5 Burke W, Petersen G, Lynch P,
Botkin J, Daly M, Garber J, et al. Cancer Genetics Studies Consortium.
Recommendations for follow-up care of individuals with an inherited
predisposition to cancer. I Hereditary nonpolyposis colon cancer.
JAMA 1997;277:915-9.
6 Vasen HF, den Hartog Jager FC,
Menko FH, Nagengast FM. Screening for hereditary nonpolyposis
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1989;86:278-81.
7 Vasen HF, Mecklin JP, Watson P,
Utsunomiya J, Bertario L, Lynch P, et al. Surveillance in hereditary nonpolyposis
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1993;36:1-4.
8 Woolf SH. The best screening
test for colorectal cancer- a personal choice. N Engl J Med 2000;343: 1643.
9 Lieberman DA, Weiss DG.
One-time screening for colorectal cancer with combined fecal occultblood testing
and examination of the distal colon. N Engl J Med 2001;345:555.
10McLeod RS. Screening strategies
for colorectal cancer: A systematic review of the evidence. Can J Gastroenterol
2001;15:647-60.
11 Bond JH. Colorectal cancer
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Clin North Am 2000;85:1163-82.
12Podolsky DK. Going the distance-the
case for true colorectal cancer screening. N Engl J Med 2000;343:207-8.
13lmperiale TF, Wagner DR, Lin
CY, Larkin GN, Rogge JD, Ransohoff DF. Risk of advanced proximal noeplasms in asymptomatic adults according
to the distal colorectal findings. N Engl J
Med 2000;3443:169-74.
14Lieberman DA, Weiss DG, Bond
JH, Ahnen DJ, Garewal H, Chejfec G. Use of colonoscopy to screen
asymptomatic adults for colorectal cancer. N Engl J
Med 2000;343:162-8. 15Ransohoff DF, Lang CA.
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background paper. Ann Intern Med. 1997;126:811-22.
16Rubin DT, Dachman AH. Virtual
colonoscopy: a novel imaging modality for colorectal cancer. Curr Oncol Rep
2001;3:88-93.
17Hara AK, Johnson CD, MacCarty
RL, Welch TJ, McCollough CH, Harmsen WS. CT colography:
single- versus multi-detector row imaging. Radiology
2001;219:461-5.
18National Cancer Institute of
Canada: Canadian Cancer Statistics 2001, Toronto, Canada, 2001. 19British
Columbia Vital Statistics Agency, Ministry of Health Services. Annual Report: Death-Related
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20Bond JH. Rectal bleeding: is
it always an indication for colonoscopy? Am J Gastroenterol 2002;97: 223-5.
21 Mulcahy HE, Patel RS, Postic
G, Eloubeidi MA, Vaughan JA, Wallace M, et al. Yield of colonoscopy in patients
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22 Health Canada. National Committee
on Colorectal Cancer Screening: Recommendations for Population-based
Colorectal Screening. Ottawa; 2002.
Effective date March 1, 2004
Adapted by N.J. Bosomworth, MD, CCFP, FCFP