Cancer Awareness and Prevention
In addition to diagnosing and treating gastrointestinal and liver disease, the physicians at Digestive Disease Associates actively promote awareness and prevention. The following article by DDA’s Dr. Theodore Burns addresses the preventable nature of colon and rectal cancer.
Colon and Rectal Cancer Prevention OR Colon Cancer is a Preventable Disease
by Theodore Burns, M.D., Gastroenterologist in private practice
If you are not inclined to read this article, at least read the first two paragraphs. If you do and subsequently in your lifetime develop colon or rectal cancer, odds are that it will be your own fault. Colorectal cancer is largely a preventable disease. Are you interested? Read on a bit and then decide for yourself what strategy you will follow personally and recommend to your patients and your family.
Prevention is the key word in the current approach to colon and rectal cancer. Early detection may be the current strategy for prostate and breast cancer; but for colorectal cancer, prevention is possible and should be a priority. Simply stated, the risk of colon cancer in the United States population can be reduced by up to 90% if asymptomatic adults 50 years of age or older undergo complete endoscopic examination of the colon every five to ten years. Such examinations would result in the systematic detection and removal of benign but precancerous polyps. These slow growing adenomas give rise to nearly all of the colon and rectal cancers in our patient population. Not every polyp will become cancerous, but nearly all cancers begin in these pre-existing adenomas. If all adenomas are removed, cancer, with few exceptions, does not occur. It is that simple.
Colon cancer arising in long standing ulcerative colitis is an exception to this rule. Additionally, there are some high risk individuals identified by family history or genetic testing to have syndromes that increase their risk and necessitate earlier screening or colectomy. For the vast majority of the population, however, screening of asymptomatic individuals beginning at age 50 and repeated at five year intervals is dramatically effective.
Well, you may say, this is great news! When did all of this information about prevention of colorectal cancer become available? How does 1974 sound? It is true that for more than 25 years there has been good evidence that screening for and removal of polyps can significantly reduce colorectal cancer. In a clinical study of monumental proportion, Gilbertsen performed annual rigid sigmoidoscopy in thousands of healthy subjects over a 20-year period and removed any polyps that were detected. Distal colorectal cancer was virtually eliminated in this patient group. This impressive study was published in the journal Cancer in 1974. This study demonstrated what had long been suspected and what has since been confirmed; colon cancer almost always arises in pre-existing, benign polyps. It was not until 1993 that the massive, multi-center National Polyps Study reinforced and extended Gilbertsen’s observations. This study confirmed that systematic colonoscopic examination of the entire colon with removal of all detected polyps at three-year intervals in asymptomatic subjects dramatically reduced the occurrence of colorectal cancer. Those few cancers that were discovered during the course of these scheduled exams were very early and curable. Subsequent information suggests that there is a little added risk in extending the interval for examinations to five years or possibly ten years when no polyps were found. Two very recent studies published in the New England Journal of Medicine have shown that if we rely on examinations of the sigmoid colon alone, approximately half of advanced adenomas and malignant lesions will go undetected in asymptomatic adults.
Let us consider some of the important elements of the colon and rectal cancer problem in this country, identify the population at risk, and review a few options for prevention.
COLORECTAL CANCER IN THE UNITED STATES
First, we need to appreciate the magnitude of the problem. Colorectal cancer is the second leading cause of cancer deaths in the United States. This year more than 51,000 Americans will die of this disease and more than 143,000 new cases will be diagnosed. The chance of developing colorectal cancer over a lifetime for the American population is over 50%. For those with a first degree relative with colorectal cancer or polyps it is higher, especially if the individual was less than 50 years of age at the time of diagnosis. When patients present with symptoms related to the disease, it is usually in an advanced state and five-year survival is less than 50%. It is appropriate at this point to be redundant and remind the reader that up to 90% of these cancers are preventable and more than 95% of the deaths are preventable if optimal screening is employed. Men and women are similarly affected and the disease cuts across racial, ethnic, and cultural demographics. It appears to be more related to environmental and developmental factors than heredity, race, or country of origin. It is by far the most common malignancy arising in the gastrointestinal tract.
The term colon polyp is a broad descriptive term that we must consider more closely to make judgments with regard to significance or cancer risk. There are three general types of polyps. “Non-neoplastic” polyps such as hyperplastic polyps, haramatomas, and inflammatory polyps are usually of little significance and are unrelated to cancer. “Submucosal” polyps such as lipomas, carcinoid tumors, metastatic lesions, leiomyomas, and others may represent significant clinical problems but are not related to colorectal cancer and are not relevant to this discussion. The third group, “neoplastic” musocal polyps include both the benign adenomas and polyps which have progressed to adenocarcinoma. It is the premalignant adenomas about which we should be concerned if we are to prevent cancer.
Based on histologic appearance, adenomas can be classified as tubular, villous or mixed tubulovillous. This distinction is important. Villous polyps grow more quickly and have a higher incidence of cancer at a given stage of development. Tubular adenomas grow more slowly, reach a larger size before undergoing malignant change, and are more common than villous polyps. Mixed tubulovillous polyps fall between the two. In general, the more villous component to a given polyp, the more likely it is to contain malignant cells or to progress to a malignancy.
Polyp size is also an important factor. It is rare to fine carcinoma in polyps that are less than 0.5cm. Polyps that are 0.5-1cm have a less than 2% chance of harboring malignant cells. This incidence increases to 10% for polyps 1-2cm in size and to 40% for polyps greater than 2cm. A villous polyp greater than 2cm has a greater than 50% chance of being malignant at the time it is detected.
Colon polyps are quite common. Autopsy and colonoscopic studies in American adults suggest an incidence of 40-50% over a lifetime. Thus, most polyps will not progress to cancer. This is in part due to a very slow growth rate for most polyps. The time period from the initial change in a colonic epithelial cell as it escapes regulatory control and begins neoplastic proliferation until this adenoma reaches a significant size and dysplastic change leading to malignancy is at least five to ten years or longer.
Most of these polyps can be safely removed during colonoscopic examination. Since there is no way to determine which polyps have significant malignant potential, all detected polyps should be removed whenever safely possible. If these polyps can not be removed colonoscopically, then the size and histologic grading on biopsy dictate recommendations for open surgical removal.
The finding of polyps in our patient population peaks at 60-70 years of age. Thus, it is quite reasonable to begin systematic screening for polyps 10-15 years before this peak incidence, or at about age 50. For those with first degree relatives with a diagnosis of colorectal cancer or polyps made before age 50, screening should begin 10-15 years earlier than the date of the diagnosis of the affected relative. Additionally, any adult with unexplained iron deficiency, gastrointestinal blood loss, unexplained abdominal pains, or change in bowel habits should be appropriately evaluated even at age 40 or 30. There is a definite trend to earlier age of onset for colon cancer and polyps in our population.
DETECTION OF POLYPS AND CANCER
There are currently two modalities available to the clinician for the detection of colorectal polyps and cancer. Barium enema radiographs have been available for decades and are still used in screening examinations in some circumstances, especially when the patient has a contraindication to colonoscopy or when anatomic factors do not allow complete colonoscopic examination. Colonoscopy is far more accurate in detecting neoplasia and offers the obvious advantage of facilitating biopsy or removal of polyps at the time of examination. Some time in the future, there may be alternatives to colonoscopy and barium enema for screening. “Virtual colonoscopy,” a computerized tomographic x-ray scan of the colon, is currently being developed and holds some promise for a noninvasive, risk-free colon exam. Recent reports of a “capsule” with a microchip camera which can be ingested and can examine the gastrointestinal tract in transit are of great interest, but very early in development. Great progress has been made in genetic testing. Individuals with polyposis syndromes can be identified genetically and some day genetic tests may help identify other polyp-formers and allow colonoscopy to be selectively applied. In a just-published report, researchers used stool analysis for altered DNA to identify polyp and cancer patients with surprising accuracy. At present colonoscopy is our best method for detection and removal of precancerous colon polyps and for early detection of invasive colon and rectal cancer.
Colonoscopy is performed in an outpatient setting after a thorough cleansing of the bowel on the preceding day. Short-acting sedatives allow a painless examination. The entire colon can be examined in more than 95% of healthy subjects and almost all resume a regular diet after the procedure and routine activities the following day. Complications can occur but in less than 0.1%. Outpatient endoscopy centers and reduction in colonoscopy fees by third party payers have made colonoscopy far less expensive than in the past. Its expense as a cancer-screening tool, when annualized, is comparable to or less than screening for breast and prostate cancer.
OTHER PREVENTATIVE MEASURES
Epidemiologic studies citing the importance of environment and diet on the incidence of colorectal cancer have led to suggestions that added fiber in the diet and increased intakes of antimutogenic and anticarcinogenic vegetables may reduce the risk of colon polyps and colorectal cancer. Antioxidant vitamins A, C, and E and folic acid have also been suggested as bring potentially beneficial. Restriction of red meat and supplementation of calcium and trace elements may be factors that can reduce the incidence of colorectal cancer. Unfortunately, when subjected to careful analysis in large population studies, evidence of the benefit of any of these measures has not been forthcoming.
There is evidence that daily aspirin and other non-steroidal anti-inflammatory agents over time may suppress or prevent new polyp growth in patients known to form polyps. Thus, these agents may be protective against colorectal cancer. This protection may be due to the inhibition of the cycloxygenase-2 pathway in prostaglandin production. High-dose celecoxib (“Celebrex”) has been approved by the FDA for use in patients with familial polyposis for the prevention or reduction of colon polyps. To be effective, such therapy must be used on a daily basis indefinitely. Because of potential side effects associated with these drugs, their use in prevention of colon polyps must be considered on a case-by-case basis and the evidence that they will be effective over a long period is certainly not established.
Based on what we now know about the relationship between colon polyps and colorectal cancer, it appears clear that preventative screening colonoscopy of healthy adults in the United States beginning at age 50 and repeated at five to ten year intervals can have a dramatic impact on the incidence and death rate from this tragic illness. Screening for individuals deemed to be at high risk must be individualized and may be indicated at age 40 or earlier. Those individuals who are found to have polyps usually require more frequent examinations, at least until all polyps have been removed. New genetic and imaging techniques may allow colonoscopy to be selectively applied to those shown to be at high risk for polyps and cancer.
As currently applied, flexible sigmoidoscopy at three to five year intervals and annual stool tests for occult blood will continue to bring asymptomatic patients with dis colorectal polyps and cancers to each diagnosis. However, it is clear that many polyps and many cancers do not bleed. Examinations limited to the sigmoid colon will fail to detect half asymptomatic, proximal adenomas cancer. Hopefully, in the future, better appreciation of the extraordinary opportunity to prevent colorectal cancer will prompt medical practitioners, policy makers, and third party payers to change our current short-sighted approach to screening for colorectal cancer.
SUGGESTED SUPPLEMENTAL READING
New England Journal of Medicine 2000:343:162-168
Gastroenterology 2000: 119:1219-1227