A comparison of fecal occult-blood tests for colorectal-cancer screening
Authors: Allison J, Tekawa I, Ransom L, Adrain A.
Source: New England Journal of Medicine. 334:155-9. January
Institution: Kaiser Permanente Medical Center.
Financial support: Kaiser Foundation; SmithKline Diagnostics.
Traditional guaiac-based fecal occult blood tests are relatively insensitive
for the detection of adenomas and cancer. Rehydrated stool guaiac cards
are more sensitive and have been shown to decrease mortality from colon
cancer, but they are less specific and lead to many false positives. Newer
approaches to FOB testing include more sensitive guaiac cards (such as
Hemoccult II Sensa), and an immunochemical test for human hemoglobin (HemeSelect).
This study was designed to compare three of these methods and a combination
Subjects: Patients of Kaiser Permanente Medical Center in Oakland, CA,
over 50 years of age, scheduled for a "personal health appraisal" examination
between October 1990 and October 1991.
Stool cards: Each patient received three stool cards, each containing three
stool tests -- Hemoccult II (conventional guaiac), Hemoccult II Sensa (more
sensitive guaiac test) and HemeSelect (immunochemical test).
Specimen collection: Collection during the three days prior to the clinic
visit, using a paper saddle device (to avoid contact of the stool with
water). Multiple dietary and medication exclusions during the week prior
to the sampling.
Stool card analysis: Each of the three tests was developped and recorded
separately. A combination test was also defined, using the Hemoccult II
Sensa and the HemeSelect -- it was positive if both tests were positive,
but negative for any other combination. Not all submitted samples were
interpretable; a subject was considered screened by a given method if there
was at least one interpretable result by that method.
Follow-up: Patients with a positive test result were evaluated, usually
by colonoscopy, except for patients who had a positive Hemoccult II Sensa
but negative other tests. When most of these patients were found to have
negative colonoscopies, the protocol was changed to recommending sigmoidoscopy
followed by repeat stool testing in 6 months.
Test evaluation: Tests were evaluated for sensitivity and specificity using
the incidence of polyps > 1cm. and colon cancer detected during the two
years following the stool collection.
8104 subjects were screened with at least one test. Age groups 50-59, 60-69
and over 70 were equally represented.
At least one test was positive in 1312 patients (16.2 %). Of these, 57%
had only a positive Hemoccult II Sensa test.
Colonoscopy was performed in over 80% of patients with positive results
on a test other than Hemoccult II Sensa. 142 neoplasms were detected, 107
polyps and 35 carcinomas.
The sensitivity and specificity of the four tests for polyps over 1 cm
and carcinoma were:
Hemoccult II: sensitivity 32%, specificity 98%
Hemoccult II Sensa: sensitivity 71%, specificity 88%
HemeSelect: sensitivity 67%, specificity 95%
Combination test: sensitivity 54%, specificity 98%
The authors feel that the combination test (Hemoccult II Sensa and,
it this test is positive, confirmatory HemeSelect testing) represents the
best approach. They assume that, as in their study, a positive Hemoccult
II Sensa with a negative HemeSelect result will be followed by flexible
sigmoidoscopy and Hemoccult II testing at 6 and 12 months. Although HemeSelect
alone has a higher sensitivity than the combination test, it has a lower
specificity and a much higher cost ($3.31 for Hemoccult II; $3.82 for Hemoccult
II Sensa and $19.23 for HemeSelect). Since about 2/3 of the combination
tests would not require HemeSelect testing, the cost of the combination
test would be significantly less than HemeSelect testing alone.
In this study, the authors test each of three different types of fecal
occult blood tests. The conventional guaiac test (Hemoccult II, here),
has good specificity, but low sensitivity (around 30%), which would entail
missing about 2/3 of cancers and polyps. The more sensitive guaiac tests,
such as rehydrated stool guaiac tests and the Hemoccult II Sensa tested
here have a much higher sensitivity, but their lower specificity would
lead to a high colonoscopy rate. Finally, the immunochemical method, which
detects human hemoglobin, has good sensitivity and specificity, but is
very expensive. The combination test combines the advantages of the sensitive
guaiac tests with the specificity of HemeSelect -- those who test negative
by the sensitive guaiac test do not need the expensive immunochemical test;
those who test positive by the cheaper test should be confirmed by immunochemistry.
In an accompanying editorial, D. Ransohoff and C. Lang state "Because
neoplasms bleed intermittently, however, the next step in the evaluation
of the combination test is to show that the sensitivity remains high when
the test is applied to sequential specimens obtained at two different times,
as Allison et al. suggest, instead of to the same specimens, as in their
study." This is not my understanding of the combination test, however,
which is not clearly defined in the article. My interpretation of the combination
test is that all patients would provide simultaneous samples for both tests,
and that the immunochemical test would only be performed if the guaiac
test turned out to be positive. This is a very important distinction. Having
a patient obtain three stool samples, followed by three more samples for
the 1/3 of patients with a positive guaiac test would not be acceptable
The authors recommend performing sigmoidoscopy and repeat stool testing
at 6 and 12 months for those with positive guaiac but negative immunochemistry
tests. Unfortunately, they do not give data on the incidence of polyps
and tumors in these patients, compared to those with negative guaiac tests.
If these incidences turned out to be the same, even the flex sig and repeat
stool testing might not be necessary, although it is hard to argue against
Assuming that the combination test is made available as a single, multi-specimen
card, it certainly would seem to represent an improved fecal occult blood
Subject: Early detection of colorectal ca
Date: Thu, 25 Apr 1996
From: DSBB78A@prodigy.com (DR RICHARD L STERN)
Remember that flexsig only studies about half of the colon. Aircontrast
barium enema or a good single contrast barium enema is necessary, because
about 30% of the significant polyps or cancers would otherwise be missed.
In this study, flexible sig was only performed in patients with an isolated
positive sensitive guaiac test (and negative immunochemical test) -- which
the authors felt represented an almost certainly falsely positive test.
For screening in asymptomatic patients, FOB and flexible sigmoidoscopy
have a role. Some have argued for a single colonoscopy at age 50, particularly
for high risk patients. The problem with using barium enema as part of
a screening strategy (in guaiac positive patients) is that any findings
such as polyps would then require a colonoscopy for polypectomy. BE vs.
colonoscopy in symptomatic patients is another question, not totally
resolved as far as I know. -- mj
June 15, 1996
to the Editor about this article from the NEJM
The question of the proper interpretation of the combination test, which
I raised in my comments about this article, were addressed and answered
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