Report in English with a Dutch summary (KCE reports 45A)

KCE reports vol.45 Screening for Colorectal Cancer 61
high, thereby minimising the number of false negatives. A highly specific test
means that there will be a high probability that the test will have a negative
result if indeed the person does not have the condition, thereby minimising the
number of false positives.
Other measures of assessing diagnostic performance in screening tests are the
predictive values (positive and negative predictive value). These measures can
be useful in clinical settings, as they indicate the probability that a person with a
given test results will indeed have or not have the disease, but they are specific
for the population in which they are used as they depend on the population
prevalence of the condition. Therefore, they should not be used while
comparing tests that were used in different populations. The same is true for
concepts such as the Number Needed to Screen (NNS) as those numbers are
dependent upon the population in which the intervention is applied.
Most trials of screening strategies have been conducted in men and women
aged 50 and up to ages 70 to 75. The obvious reason, of course, is to apply the
test in a population with sufficiently high prevalence of detectable
malformations.
5.4.1 Fecal occult blood tests (FOBT)
Fecal occult blood testing (FOBT) is based on the nature of colorectal cancer
and larger polyps to bleed intermittently. Presence of blood in the stool is
therefore an indicator of cancer. The bleeding, however, is intermittent and
blood is unevenly distributed throughout the stool. Additionally, the amount of
bleeding is dependent on the size of the polyp(s) or cancer. Screening for the
presence of blood in the stool is far less sensitive for polyps than for cancer 265.
Approximately two thirds of colorectal cancers bleed in the course of a week 266
, 267, 197, thereby naturally limiting the potential clinical sensitivity of FOBT: at the
moment the cancer does not bleed it can not be detected by FOBT. Moreover,
non-malignant lesions can also bleed and there are still other causes for the
presence of blood in the stool, thereby also limiting the potential specificity.
FOBT is therefore, by definition, a non-specific test giving information on the
probability of the presence of colorectal cancer. It provides no information on
the localisation of the source of bleeding, but it has the advantage of being a
non-invasive test. Therefore, a positive test result will necessarily call for an
invasive procedure afterwards 268.
Most information in the literature is found on the classical FOBT, the so-called
guaiac FOBT (gFOBT). Van Deen 269 is generally credited with the discovery that
gum guaiac, a natural resin extracted from the wood of Guaiacum officinale, is
useful in detecting occult blood. The heme portion of hemoglobin, if present in
the fecal specimen in its free form or bound to protein (globin, myoglobin, and
some cytochromes), has peroxidase activity which catalyzes the oxidation of
alpha guaiaconic acid (active component of the guaiac paper) by hydrogen
peroxide (active component of the developer) to form a highly conjugated blue
quinone compound. Degradation products of heme, that are formed in the
intestine, lack peroxidase activity and, as a result, are not detected by the test.
Heme enters the proximal gastrointestinal tract as hemoglobin or myoglobin in
food or as red cells from bleeding lesions, and relatively little is absorbed by the
small intestine. However, in the colon, heme is modified by the microflora so
that it loses its peroxidase activity, and consequently guaiac tests are more
sensitive for distal (colonic) than for proximal (gastric) bleeding pathology.
To perform the test, fecal matter needs to be collected and applied to a testing
kit. Guaiac-based FOBTs use sticks or spatulas to collect specimens from stools