Screening
Colorectal cancer is the third commonest malignancy in the
United Kingdom, after lung and breast cancer, and kills about
20 000 people a year. It is equally prevalent in men and women,
usually occurring in later life (at age 60-70 years). The incidence
of the disease has generally increased over recent decades in
both developed and developing countries. Despite this trend,
mortality in both sexes has slowly declined. This decrease in
mortality may reflect a trend towards earlier diagnosis—perhaps
as a result of increased public awareness of the disease.
Why screen?
Most colorectal cancers result from malignant change in polyps
(adenomas) that have developed in the lining of the bowel
10-15 years earlier. The best available evidence suggests that
only 10% of 1cm adenomas become malignant after 10 years.
The incidence of adenomatous polyps in the colon increases
with age, and although adenomatous polyps can be identified in
about 20% of the population, most of these are small and
unlikely to undergo malignant change. The vast majority (90%)
of adenomas can be removed at colonoscopy, obviating the
need for surgery. Other types of polyps occurring in the colon—
such as metaplastic (or hyperplastic) polyps—are usually small
and are much less likely than adenomas to become malignant.
Colorectal cancer is therefore a common condition, with a
known premalignant lesion (adenoma). As it takes a relatively
long time for malignant transformation from adenoma to
carcinoma, and outcomes are markedly improved by early
detection of adenomas and early cancers, the potential exists to
reduce disease mortality through screening asymptomatic
individuals for adenomas and early cancers.
Which screening test for population
screening?
Education about bowel cancer is poor. A survey in 1991 showed
that only 30% of the British population were aware that cancer
of the bowel could occur. Such ignorance only adds to the
difficulties of early detection for this form of cancer.
For a screening test to be applicable to large populations it
has to be inexpensive, reliable, and acceptable. Many different
screening tests for detecting early colorectal cancer have been
tried. The simplest and least expensive is a questionnaire about
symptoms, but this has proved predictably insensitive and
becomes reliable only when the tumour is relatively advanced.
Digital rectal examination and rigid sigmoidoscopy both suffer
from the limitation that they detect only rectal or rectosigmoid
cancers and are unpleasant and invasive.
Flexible sigmoidoscopy
Flexible sigmoidoscopy can detect 80% of colorectal cancers as
it examines the whole of the left colon and rectum. A strategy of
providing single flexible sigmoidoscopy for adults aged 55-65
years—with the aim of detecting adenomas—may be cost
effective. A multicentre trial of this strategy for population
screening is currently under evaluation.
Although flexible sigmoidoscopy is more expensive than
rigid sigmoidoscopy, it is generally more acceptable to patients
(it is less uncomfortable) and has much higher yield than the
rigid instrument. Many nurses are now trained to perform
flexible sigmoidoscopy, making potential screening
programmes using this technique more cost effective. In a
population screening programme, uptake of the offer of the
screening test is crucial. Uptake is likely to be around 45%, and,
of these, 6% will subsequently need full colonoscopy. The effect
that this will have on the incidence of and mortality from
colorectal cancer is uncertain until the completion of the
multicentre trial in 2003.
Colonoscopy
Colonoscopy is the gold standard technique for examination of
the colon and rectum, but its expense, the need for full bowel
preparation and sedation, and the small risk of perforation of
the colon make it unacceptable for population screening.
Colonoscopy is, however, the investigation of choice for
screening high risk patients (those at risk of hereditary
non-polyposis colon cancer or with longstanding ulcerative
colitis).
Barium enema
Barium enema, like colonoscopy, examines the whole colon and
rectum, and, although it is cheaper and has a lower
complication rate than colonoscopy, it is invasive and requires
full bowel preparation. Whereas colonoscopy may be
therapeutic (polypectomy), barium enema does not allow
removal or biopsy of lesions seen. There are no population
screening studies using barium enema.
Faecal occult blood tests
Faecal occult blood tests are the most extensively studied
screening tests for colorectal cancer. These tests detect
haematin from partially digested blood in the stool. Their
overall sensitivity for colorectal neoplasia is only 50-60%,
though their specificity is high. In screening studies of faecal
occult blood tests, individuals are invited to take two samples
from each of three consecutive stools. Compliance is around
50-60%, but with population education this might be improved.
Individuals with more than four out of six positive tests (about
2% of participants) need colonoscopy.
Several large randomised studies have shown that screening
with faecal occult blood testing is feasible, and two studies have
shown that such screening reduces the mortality from
colorectal cancer. In a study in Nottingham, for every 100
individuals with a positive test result, 12 had cancer and 23 had
adenomatous polyps. The cancers detected at screening tended
to be at an earlier stage than those presenting symptomatically
(Dukes’s A classification: 26% screen detected v 11% in
controls). The disadvantage of screening with faecal occult
bloods is its relatively low sensitivity—a third to a half of cancers
will be missed on each round of screening. The Nottingham
data suggest that screening every two years detects only 72% of
cancers. This could be improved by testing annually and using
more sensitive immunologically based faecal occult blood tests.
Who should be screened?
Although about 20% of the population will develop
adenomatous polyps, only 5% of these will develop colorectal
cancer. This equates to a 1 in 20 lifetime risk for colorectal
cancer. The cancer occurs most often in the age group 65-75
years, but for adenomas the peak incidence is in a slightly
earlier age group (55-65 years). Thus population screening for
colorectal cancer should target both these age groups.
In addition, some people inherit a much higher
susceptibility to colorectal cancer. Some inherit a well
recognised single gene disorder, such as familial adenomatous
polyposis or hereditary non-polyposis colon cancer, whereas
most inherit an undetermined genetic abnormality. These
people tend to develop colorectal cancer before the age of 50,
and therefore screening in this high risk population needs to be
tailored to each individual’s risk pattern. They may also be at
risk for cancers at other sites, and screening for ovarian, breast,
and endometrial cancers may be appropriate in some of these
cases. The advice of clinical geneticists in these cases can be
invaluable.
Cost effectiveness of screening
If screening for colorectal cancer is to be acceptable to
healthcare providers it must be shown to be cost effective.
Estimates of the cost of screening for colorectal cancer range
from £1000 to £3000 per life year saved, depending on the
screening technique used. The cost of using faecal occult blood
testing would be the lowest—similar to estimates for breast
cancer screening.
Cost estimates are associated with several unknown factors.
The factors that cause greatest concern to those considering
funding screening programmes are the cost of cancers missed
and the potential damage caused to asymptomatic individuals
by invasive procedures such as colonoscopy.
Potential harm from screening
Although it has been suggested that considerable anxiety and
psychological morbidity may be caused by inviting populations
to participate in screening for colorectal cancer, little evidence
exists to substantiate this. Indeed in the Nottingham trial no
longstanding psychological morbidity from the screening
programme was found. Similarly, no evidence exists that
screening for colorectal cancer leads to false reassurance from
negative tests.
Complications from colonoscopy (perforation and
haemorrhage), however, can occur. The incidence of these
complications is around 1 in 2000 procedures, and
complications usually occur in therapeutic colonoscopy
(endoscopic polypectomy) rather than in diagnostic procedures.
Mortality from such events is rare.
