Special Focus Prevention of Colorectal Cancer—How Do We Do It Best? Clement Richard Boland, MD, AGAF Chief of Gastroenterology, Baylor University Medical Center (BUMC), Dallas, Texas
Colorectal cancer (CRC) is a common disease but unique in the degree to which cancer-related mortality can be reduced by appropriate screening and surveillance programs. The progress has been steady and impressive over the past three decades, but where do we stand in our quest for excellence?
In 1978, we learned that we could nearly eliminate deaths from rectal cancer with periodic proctosigmoidoscopy and polyp removal.1
No other
cancer-screening strategy makes such a bold promise. The early 1980s brought us detection of asymptomatic colorectal neoplasms using a guaiac-based fecal occult blood test (g-FOBT), which helped find more neoplasms, and significantly more early-stage (I or II) tumors.2,3
A
g-FOBT-based program can reduce CRC mortality by 33% if performed annually,4
but low compliance or carrying out the test biannually compromises its performance.5,6
When sigmoidoscopy was found to reduce CRC mortality in the examined portion of the bowel by as much as 70%,7,8
we aimed for a
similar reduction in incidence and mortality throughout the colon in asymptomatic individuals with a program of colonoscopy. This has become our standard of practice despite the lack of prospective randomized studies. More recent studies have confirmed that once-only flexible sigmoidoscopy prevents rectosigmoid cancers9
and
reduces incidence (by 23%) and mortality (by 31%) of all CRCs and a significant (50%) reduction in the incidence of cancer in the distal colorectum, without a significant reduction in proximal tumors.10
This
is a benefit not achieved with mammography for breast cancer, or any technique for the detection of prostate or other common cancers. However, sigmoidoscopy does not prevent incident or lethal proximal CRCs, the location of ~25–30% of colorectal tumors in the US.
The ability of colonoscopy to protect against CRC is not uniform throughout the colon. Several studies have shown reductions in distal CRC by 67%,11
56%,12 and 66%,13 whatsoever in the proximal colon.
How do we deal with this complexity in the prevention of CRC? First, we need to do our best to ensure careful inspection of the proximal colon, with the removal of every lesion, including flat adenomas. These are easily missed and may be precursors of CRCs with microsatellite instability (MSI), which may progress from adenoma to carcinoma more rapidly than sporadic neoplasms in the distal colon. Second, let us consider whether we have already improved the
© TOUCH BRIEFINGS 2010 but with limited or no protection
detection of proximal lesions—with better optics and enhanced awareness of the importance of small adenomas in the proximal colon—but have not yet measured the benefit. Also, about half of the tumors in the proximal colon have MSI, and these tumors have a significantly better natural history than do those without this genetic perturbation (at least in young patients);14
this might explain the
inability to reduce cancer-related deaths in the proximal colon. There are multiple variables in this problem, including natural differences in the biology of the tumors and secular trends in the technologies we use to detect them.
Finally, we may find ourselves re-exploring the use of flexible sigmoidoscopy—the data support a very impressive reduction in cancer incidence and mortality using this approach—in combination with another technology to detect early lesions in the proximal colon. This might include newer-generation FOBTs (such as immunochemical tests) or testing fecal DNA (reviewed by Lieberman).15
Computed
tomography colonography has not been widely embraced because of the low sensitivity for small lesions and the radiation exposure, but it has not been specifically examined for its ability to detect proximal lesions. g-FOBTs are less effective the farther the neoplastic lesion is from the anus because of progressive degradation of the peroxidase activity of the heme,16
but the immunoreactivity of globin or
detectability of fecal DNA may be just as good when it comes from proximal lesions. Importantly, not all approaches have been examined yet for differential sensitivity between the sides of the colon. It is often a great surprise to discover that we are not getting the benefit of diagnostics that we had assumed. The biggest mistake we can make is to conclude that we cannot make it better. n
Clement Richard Boland, MD, AGAF, is Chief of Gastroenterology at Baylor University Medical Center (BUMC) in Dallas, Texas, and President Elect of the American Gastroenterology Association. He has a career-long research interest in colon cancer, specifically focusing on the causes of colon cancer and familial cancer syndromes. He was among the first gastroenterologists to explore the area of microsatellite instability in cancer, and his laboratory developed in vitro models for the study of
Lynch syndrome using stable chromosome transfer to correct DNA mismatch repair deficiencies in cultured cells. At BUMC, he has focused entirely on colon cancer research in both laboratory-based and clinical programs designed to accelerate the translation of basic concepts into diagnostic, preventive, and treatment approaches for clinical medicine, including the mechanisms by which inflammation predisposes to cancer in the gastrointestinal tract, and prevention strategies, some of which utilize compounds in foods that are commonly eaten in populations with low CRC incidences.
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