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

KCE reports vol.45 Screening for Colorectal Cancer 91
There were also no published RCTs of the use of stool DNA mutation tests as
a screening strategy for colorectal cancer. Those DNA mutation tests were
recently assessed in a prospective study of 4.404 asymptomatic persons who all
received colonoscopy 339, 246. Hemoccult II was compared to a stool DNA testing
based on a panel of markers assessing 21 mutations. Conducted in a blinded
way among a subgroup of 2.507 participants the DNA panel had a much better
sensitivity than Hemoccult II for all stages of colorectal cancers with a similar
specificity.
A cost-effectiveness analysis of colorectal cancer screening with stool DNA
testing in the general population 50 to 75 years of age in Taiwan 342, compared
with annual FOBT, FS every 5 years, and colonoscopy every 10 years or not
screening at all, concluded that, in countries with a low or intermediate
incidence of colorectal cancer, stool DNA testing is less cost-effective than the
other currently recommended strategies for population-based screening,
particularly targeting at asymptomatic subjects.
Fecal DNA testing may provide enhanced sensitivity for detection of CRC in
comparison with FOBT, but its high cost limits its use for generalized screening.
Rectal mucin testing requires additional evaluation to determine its sensitivity
and specificity in comparison with guaiac-based FOBT. Serum tests, such as
proteomics, nuclear matrix proteins, and serum DNA, are still in their infancy,
but remain a hope for the future 264.
5.6 POTENTIAL HARMS OF CRC SCREENING
5.6.1 False positive results, overinvestigation and complications of colonoscopy
Screening comes at a cost, and the cost is not only financial but can also be
measured in terms of morbidity and mortality. The question of financial cost is
dealt with in the section on economic evaluation, but the issues on morbidity
and mortality are as important. While performing a FOBT is unlikely to cause
physical morbidity and FS is very safe, the possibility of complications of the
subsequent colonoscopy for those with a positive test and of surgery for those
who are diagnosed with cancer should not be overlooked. Estimates of postscreening
colonoscopy harms depend on the trial: for the Minnesota trial there
would be 28 percent of the participants having at least one colonoscopy (the
Minnesota trial used rehydrated Hemoccult increasing sensitivity at the expense
of specificity and had therefore higher colonoscopy rates) and there would be
0,34 pro mille colonoscopy complications (perforations or hemorrhage).
Considering screening harms from the Göteborg RCT (non rehydrated FOBT)
there would be only 6 percent participants needing a colonoscopy, resulting in
0,18 pro mille complications.
Small adenomas (i.e., < 1 cm in diameter) are unlikely to bleed and are unlikely
to harbor malignancy 391-393. Positive screening tests for fecal blood that are
followed by colonoscopy and the discovery of small adenomas are likely to
reflect false-positive test results due to diet or non-neoplastic gastrointestinal
bleeding and the coincidental discovery of adenomas. As a result, Ransohoff and
Lang (1990) 394 suggest that, (quote) The identification of persons with small
adenomas should not be assumed to be an important beneficial outcome of
FOBT screening, because the clinical significance of small adenomas is not clear,
the mechanism of detection is serendipity, and only a minority of persons with
small adenomas are identified. The authors further suggest that more intensive
surveillance beyond average risk guidelines following removal of small adenomas
is unnecessary in such patients.