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

82 Screening for Colorectal Cancer KCE reports vol.45
These publications suggest the following conclusions regarding the comparative
performance of gFOBTs and iFOBTs:
iFOBTs have better (clinical) sensitivity than Hemoccult II but
not necessarily better sensitivity than Hemoccult SENSA,
iFOBTs have better (clinical) specificity than Hemoccult SENSA,
but specificity is not clearly as good as or better than Hemoccult
II.
However, this overall comparison assumes that iFOBTs as an assay class
perform similarly. As shown in Table 12, this may not be the case, and iFOBTs
vary in their detection limit, determined by adding known quantities of fresh,
human blood. For example, MonoHaem has the highest detection limit for
hemoglobin and, judging from 1 small study 371, poor clinical sensitivity compared
to Hemoccult II. However, the InSure assay reportedly has a detection limit that
is 6 times lower than that of FlexSure but in 1 study 377. InSure and FlexSure
performed equally. Thus, artificially determined detection limits may not predict
comparative clinical performance.
Nevertheless, evidence in favor of the substitution of gFOBT by iFOBT is
increasing, the gain being more important for high-risk adenomas than for
cancers. Automated reading technology allows the choice of the positivity rate
associated with an ideal balance between sensitivity and specificity. In a very
recently published article Guittet et al. 379 compared the performances of a nonrehydrated
gFOBT test (Hemoccult II) and an iFOBT test with automated
reading process (Magstream 1000), enabling the comparison between different
positivity cut-off points, in an average-risk population sample of the 10.673
individuals aged 50-74 years in the geographic area of Calvados (Normandy,
France), who completed the two tests. Patients with at least one test positive
were asked to undergo a colonoscopy. Accuracy of both tests was compared by
calculating the ratio of sensitivities (RSN) and the ratio of false positive rates
(RFP). Using the usual cut-off point of 20ng/ml hemoglobin, the gain in sensitivity
associated with the use of iFOBT (50% increase for cancer and 256% increase
for high-risk adenoma) was balanced by a drop in specificity. The number of
extra false positives associated with the detection of one extra advanced
neoplasia (cancer or high-risk adenoma) was 2,17 (95% CI: 1,65 - 2,85). With a
threshold of 50ng/ml, iFOBT detected more than twice as many advanced
neoplasias as the gFOBT (RSN = 2,33), without any loss in specificity (RFP =
0,99). With a threshold of 75ng/ml associated with a similar positivity rate to
gFOBT (2.4%), the use of iFOBT allowed a gain in sensitivity of 90% and a
decrease in false positive rate of 33% for advanced neoplasia.
5.5.3 Flexible Sigmoidoscopy (FS)
5.5.3.1 Telemark Polyp Study 1 - NORCCAP
No large-scale RCT has been completed. Only the Telemark Polyp Study in
Norway (the Telemark Polyp Study 1 - NORCCAP) 380, 381, which was in fact a
small feasibility study, compared a once-only FS screening to no-screening in a
control group of individuals. 400 men and women aged 50 - 59 years were
randomly drawn from the population registry of Telemark, Norway (in 1983).
They were offered a FS and, if polyps were found, a full colonoscopy with
polypectomy and follow-up colonoscopies in 1985 and 1989. A control group of
399 individuals, who were unaware of their enrolment, was drawn from the
same registry. In 1996 both groups (aged 63 to 72 years) were invited to have a