From OncoLog, Feburary 2004, Vol. 49, No. 2
Colorectal Cancer Screening: Encouraging Compliance Today and Looking to the Future
by Sunni Hosemann
What if there were
a way to cut in half the number of deaths due to colorectal cancer each
year, but patients were unlikely to ask for it, insurance companies were
reluctant to pay for it, and physicians sometimes failed to recommend
it?
According to Bernard Levin, M.D., a professor of medicine and vice president
of the Division of Cancer Prevention at The University of Texas M. D. Anderson Cancer Center, if the screening methods we have in hand today
were fully deployed—if all of the people in recommended populations
were screened—the death rate from colorectal cancer would drop by
50%. Of course, the compliance rate for any screening measure will never
reach 100%, but prevention researchers at M. D. Anderson are working to
make colorectal screening more accurate, more convenient, and more common,
even as they study ways to prevent colorectal cancer altogether.
The importance of screening
Colorectal cancers
begin as adenomatous polyps. For now, the goal of screening is to detect
and remove these precursor lesions, as well as early-stage cancers, when
they are curable. “If we can find it early, we can cure it,”
said Stanley Hamilton, M.D., a professor and head of M. D. Anderson’s
Division of Pathology and Laboratory Medicine.
The biology of colorectal cancer makes it particularly amenable to screening:
colorectal cancers are associated with a low probability of metastasis
in early-stage disease, and a variety of effective screening tools can
be employed to detect polyps and early-stage cancer. “It is therefore
frustrating to see patients present with metastatic colorectal cancer
who have never been screened,” Dr. Hamilton said.
The screening tools of today
Current recommendations
call for colorectal cancer screening in the general population after age
50 using flexible sigmoidoscopy and a fecal occult blood test (FOBT),
double-contrast barium enema, or colonoscopy. Medically, all of these
tools are very effective, but they are not ideal, and compliance is difficult
to achieve.
Colonoscopy has some advantages over other methods because it provides
direct visualization of the entire colon, along with the opportunity to
sample or remove significant lesions. However, colonoscopy is more expensive
and more invasive than many other screening methods, and it carries a
higher risk of complications. Moreover, it is not covered by many health
insurance plans as a primary screening device. “So, should we be
doing it? Yes,” said Dr. Hamilton, “because this is one of
the cancers where screening will make a difference in the number of deaths
today.”
But the fact is that most people are not eager to undergo any of the colorectal
cancer screening procedures currently available. Therefore, in addition
to efforts to encourage screening by raising awareness of its benefits,
research is under way to find screening tools that will be better accepted
and more readily used.
A better FOBT
FOBT is the least invasive of the screening methods, but it must be used
in combination with other screening tests. A new type of FOBT—an
immunochemical method—employs antibodies to detect hemoglobin in
stool and has significant advantages over the traditional guaiac-based
method. One advantage is that it does not react with ingested food, vitamins,
or drugs to cause false-positive test results. Another is that the specimen
is collected from the surface of the stool with a brush and transferred
to a card, a much easier collection method than that required for guaiac-based
testing. Data from trials in large screening populations are not yet available,
but based on the known enhanced sensitivity and specificity and other
advantages of this method, the “American Cancer Society Guidelines
for the Early Detection of Cancer, 2004” now recommends its use
over guaiac-based testing.
New visualization tools
Two new visualization techniques have attracted the attention of the public
and the medical community, but neither is ready for use as a large-scale
screening test. Computed tomographic (CT) colonography, popularly known
as “virtual colonoscopy,” is an imaging procedure in which
a series of helical CT scans of the patient’s colon are rendered
by computer into slices that can be visualized as still, rotatable images
or serially combined to provide a three-dimensional tour of the colon.
So far, this technique has been evaluated only in small trials, mostly
conducted in diagnostic (rather than screening) settings in higher-risk
patients. The results of those studies indicate that CT colonography is
comparable to conventional colonoscopy for the detection of neoplasms
and polyps larger than 10 mm but may be less effective at detecting smaller
polyps.
Although CT colonography may eventually become an important and widely
used screening tool, a few obstacles must be overcome first. The amount
of irradiation required for CT colonography is a concern, and the technique
requires bowel preparation and insufflation (the two factors that account
for most of the objections to colonoscopy) but does not allow for removal
of polyps during the procedure, as does colonoscopy. In addition, CT colonography
requires a radiologist experienced with the technique (and the learning
curve is somewhat high), and no standards exist for performing or interpreting
the scans. CT colonography is performed at M. D. Anderson as part of research
studies, but according to Dr. Levin, it is not ready to be used as standard
care. “It is not specific enough in differentiating between significant
and nonsignificant lesions inside and outside of the colon and therefore
may prompt additional, unnecessary testing,” he said. “Nevertheless,
the technique is evolving rapidly and may become much easier to perform
and thus more acceptable to the public.”
Capsule video endoscopy—the “camera-in-a-capsule” technique—has
also attracted a good deal of attention. When swallowed, the capsule provides
approximately eight hours of videography of the digestive tract. To date,
the battery life of the device is one of its limiting factors: it usually
runs out before the capsule reaches the lower intestinal tract. Nevertheless,
it has been shown to be safe and effective in animal and clinical studies.
The wider lumen of the colon poses additional challenges in visualization,
so major refinements in equipment and technique will be needed before
capsule video endoscopy can be considered for the screening or diagnosis
of colorectal cancer.
Genetic and proteomic tumor markers
In the near future, testing stool for tumor DNA may prove more effective
than testing for occult blood. Tumors bleed intermittently, but they shed
DNA constantly, so markers would be present in any stool sample. Researchers
are still determining the best set of markers to include in a test to
screen the general population. For more than a decade, Dr. Levin has been
collaborating with scientists at The Johns Hopkins University to develop
a method for molecular testing.
Yet another area of promise and intense research is serum proteomics—the
study of protein patterns circulating in the blood. Such patterns can
have a high predictive value, and researchers are working to identify
these patterns and develop tests that will recognize them as markers of
colorectal cancer.
These methods promise to have a dramatic impact on colorectal cancer screening.
Identifying genetic and proteomic tumor markers has the potential to yield
highly sensitive and specific tests that are also less invasive (with
fewer associated risks), more convenient, and less expensive than current
screening tools. “This would result in a tremendous improvement
in compliance and effective screening,” said Dr. Hamilton, “and
would move the more invasive procedures such as colonoscopy to a diagnostic,
rather than screening, role.”
Chemoprevention
“One of the challenges in studying any intervention,” said
Patrick Lynch, M.D., an associate professor in the Department of Gastrointestinal
Medicine and Nutrition, “is to agree upon what it is important to
prevent: an endpoint.” In the interest of time and feasibility,
most colorectal cancer prevention trials today do not focus on cancer
occurrence but rather on the incidence of polyps.
Calcium and aspirin are the most recent significant findings in the search
for colorectal cancer chemopreventive agents. Laboratory, clinical, and
epidemiological evidence has long suggested that calcium may help prevent
colorectal adenomas, and clinical trials showed a moderate—but significant—reduction
in the risk of recurrent colorectal adenomas. In recent landmark studies,
a multi-institutional group of researchers that included Robert Bresalier,
M.D., professor and chair of the Department of Gastrointestinal Medicine
and Nutrition at M. D. Anderson, showed that aspirin reduced the incidence
of adenomas. Interestingly, in these and subsequent studies, low-dose
baby aspirin (81 mg) worked better than adult aspirin (325 mg).
Current chemoprevention trials are studying cyclooxygenase 2 (COX2) inhibitor
agents rather than aspirin. Both are nonsteroidal anti-inflammatory drugs
(NSAIDs) and have similar attributes; however, COX2 inhibitors have fewer
side effects than does aspirin, a nonspecific NSAID that affects both
COX1 and COX2 receptors.
Researchers at M. D. Anderson, in collaboration with those at St. Mark’s
Hospital and Academic Institute, London, England; the National Cancer
Institute; and Pfizer, Inc., conducted a study of patients with familial
adenomatous polyposis (FAP) who had dozens to hundreds of polyps. In the
study, COX2 inhibitors reduced the number of polyps by 30%. “This
didn’t necessarily prevent cancer or obviate the need for surgery,
but it served as proof of the principle that this drug can reduce polyps,”
said Dr. Lynch.
COX2 inhibitors also are being studied in a pediatric trial of carriers
of FAP susceptibility genes to determine whether they can delay onset.
“This will not be a cure, and it does not change the need for endoscopic
surveillance and frequent screening in these patients,” said Dr.
Lynch, “but it may delay surgery for youngsters in whom colectomy
is often necessary at a young age.”
Polyp precursors
A new M. D. Anderson prevention trial led by Dr. Bresalier is enrolling
patients who are at increased risk for colon or rectal cancer. In the
study, aspirin, sulindac, and ursodiol will be evaluated as potential
chemopreventive agents. Rather than using cancer or polyps as endpoints,
however, this study will look at aberrant crypt foci (ACF), micropolyps
that develop before (macro)polyps. Investigators use a special spray dye
with illumination that makes these dysplastic spots visible during colonoscopy.
The effect is dramatic: in a patient with FAP, for example, there are
perhaps five to 15 visible polyps but literally hundreds of precursor
spots.
This method takes investigators one step back in the chain of screening
markers, from studying polyps as cancer precursors to studying ACF as
polyp precursors. “The advantage is that we gain useful information
with smaller samples in a shorter period of time,” said Dr. Lynch.
Diet and vitamins
Although there seems to be a relationship between diet and the development
of colorectal cancer, such a link has not been proved. “There was
disappointing news from clinical trials in the past couple of years that
ran contrary to epidemiologic data that suggested that fiber in the diet
was associated with low risk,” said Dr. Lynch.
And despite the interest in the role of vitamins and other dietary supplements
in the prevention of colorectal cancer, only calcium has been proved effective.
Some epidemiologic data suggest that antioxidants found in fruits and
vegetables may confer some protection, but thus far, no convincing evidence
has been found to support vitamin supplementation for colorectal cancer
prevention.
Tomorrow, research may lead to better recommendations about diet, discover
more chemopreventive agents, and deliver screening tools that patients
and doctors are more willing and able to use. Meanwhile, most experts
recommend colorectal cancer prevention strategies that include periodic
screening, regular exercise, a diet high in vegetables and fruits, and
in individuals at high risk, chemoprevention using agents such as calcium.
For more information on this topic or for questions about M. D. Anderson’s treatments, programs, or services, call askMDAnderson at (877) MDA-6789.
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