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

KCE reports vol.45 Screening for Colorectal Cancer 79
A recently published meta-analysis of controlled trials on colorectal cancer
screening by FOBT 209 reviewed in depth the effectiveness of screening for CRC
with FOBT and they also included the French study results, not taken up in
previous meta-analyses. The aim was to consider the reduction in mortality
during or after screening and to try to identify factors associated with a
significant mortality reduction. A meta-analysis of four controlled trials, selected
for their biennial and population-based design, was conducted. The main
outcome measurements were mortality (RR and 95% CI) of biennial FOBT
during short (10 years, i.e. five or six rounds) or long-term (six or more
rounds) screening periods, as well as after stopping screening and follow-up
during 5 - 7 years. The meta-analysis used the Mantel-Haenszel method with
fixed effects when the heterogeneity test was not significant, and to additionally
test for potential impact of heterogeneity they excluded each of the studies in
turn. Analysis was on an 'intention to screen' basis. Although the quality of the
four trials was high, only three were randomized (Nottingham, Funnen and
Minnesota), and one (Minnesota) used rehydrated biennial FOBT associated
with a high colonoscopy rates (28%) due to the higher sensitivity and the lower
specificity of the rehydrated test. A meta-analysis of mortality results showed
that subjects allocated to screening had a 14% reduction of CRC mortality
during a 10-year period (RR 0,86; CI: 0,79 - 0,94), although CRC mortality was
not decreased during the 5 to 7 years after the 10-year (six rounds) screening
period, nor in the last phase (8 - 16 years after the onset of screening) of a
long-term (16 years or nine rounds) biennial screening. Whatever the design or
the period of ongoing FOBT, CRC incidence neither decreased nor increased,
although it was reduced for 5 - 7 years after the 10-year screening period.
Neither the design nor the clinical or demographic parameters of these trials
could be shown to be independently associated with CRC mortality reduction.
Whatever the endpoint chosen for mortality assessment in the meta-analysis,
there was never a significant decrease in overall mortality from all causes. This
is, however, not surprising because CRC mortality represents only a small
proportion of overall mortality in both the intervention groups and the control
groups (range 2,84 to 3,59%). The authors concluded that biennial FOBT
screening decreased CRC mortality by 14% when performed over 10 years,
without evidence-based benefit on CRC mortality when performed over a
longer period.
In conclusion: performing an annual fecal occult blood test (FOBT) is one of
several recommended options for colorectal cancer screening in the average
risk population beginning at age 50. Annual or biennial screening with gFOBT
has been shown in large, randomized trials to have a significant and beneficial
effect on colorectal cancer incidence and mortality, but there was never a
significant decrease in overall mortality from all causes. Furthermore, while the
specificity of these tests is generally high, sensitivity is poor. Complicated
dietary restrictions prior to testing and sampling instructions may limit patient
compliance.
5.5.2 Immunochemical Fecal Occult Blood Tests
Newer immunochemical FOBTs (iFOBT) are reported to have improved
performance characteristics compared to guaiac tests without a need for
dietary restrictions. However, no large scale prospective RCTs of iFOBT
screening and CRC incidence or mortality outcomes have been reported so far.
On the other hand, if iFOBTs perform at least as well as gFOBT, it is likely that
iFOBTs used for CRC screening would have at least the same efficacy in
decreasing CRC mortality as gFOBTs 270.