Introduction

Colorectal cancer is second only to lung cancer as a leading cause of cancer related death in the United States. There are approximately 60,000 deaths and over 160,000 new cases each year. Over the last 25 years, there has been a significant advancement in the understanding of the biology of colon cancer and in the development of methods to detect precancerous lesions or early cancers. It has been estimated that if the standard recommendations for colon cancer screening were applied to all U.S. citizens, the risk of dying from colon cancer would be less than half of what it is today. Unfortunately, because there is not complete uniformity in the medical community about implementing colon cancer screening and because many patients are reluctant to undergo what are perceived to be embarrassing or unpleasant tests, fewer than 25% of patients undergo optimal screening.

The purpose of this review is to bring you up to date to the current recommendations for colon cancer screening. It is hoped that, with this understanding, patients will enthusiastically (or at least without hesitation) undergo the appropriate examinations.



NATURAL HISTORY: The Polyp-Cancer Sequence

Before giving a detailed explanation of the methods for colon cancer screening, it is important to have an understanding of the natural history of colorectal cancer so that you will have a better understanding of why the screening tests are helpful. The current concept is that the vast majority of colon cancers arise from colon polyps. Polyps are growths of abnormal tissue in the colon. There are two broad categories of polyps: non neoplastic and neoplastic. Non neoplastic polyps are not precancerous and carry no risk. The most common form of non neoplastic polyp is called a hyperplastic polyp. Neoplastic polyps are the type that are precancerous. The most common type of neoplastic polyp is called an adenoma. Not all adenomas become cancer but a certain percentage of them do degenerate into cancer as they grow. Fortunately, polyps grow very slowly, at an estimated rate of about 2 mm per year. Because of the risk of a polyp becoming cancerous is size dependent, it is estimated that, on average, it takes about 10 years for a polyp to grow and degenerate into a cancer. If this polyp is found anytime during that 10 year period and removed, the cancer can be prevented. In addition, even if there is cancer in a polyp, removal of the polyp most often is curative, and no additional treatment is needed. So, the goal of cancer screening is to find polyps while they are still small, easy to remove, and have not yet become cancerous.


Risk Factors

The major risk factor for developing colorectal carcinoma is age. That risk begins to increase at age 40 and is very significant at about age 50 with over 90% of cancers occurring in patient’s age 50 or older. In fact a 50 year old person has approximately a 5% chance (1/20) of developing colorectal cancer by age 80. Because of this age-dependent risk (average risk), most experts recommend starting colon cancer screening at age 50 as long as patients have no additional risk factors. There are clearly groups of patients who are at higher than average risk for development of colorectal cancer (Table 1).

Once the patient has had an adenoma or a colorectal cancer, he or she has a 30-50% chance of growing new polyps. This is significantly higher than the 10-20% risk estimated for the general population.

There are several types of family history that put patients at increased risk. The two highest risk conditions are autosomal dominant diseases meaning that up to 50% of family members can be affected. These conditions are called familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC) syndromes. Patients with FAP can usually be recognized during their teenage years because they will develop literally hundreds of polyps in the colon. All patients with FAP will develop cancer if not treated. Therefore family members of patients with FAP require intensive surveillance (details to be discussed later). However, HNPCC may not be so easy to recognize because patients with this syndrome may not have a very large number of polyps. The family history that is most consistent with HNPCC would meet what is referred to as the Amsterdam Criteria: 1) at least three relatives with colorectal cancer with one being a first degree relative (parent, sibling or child) of the other two, 2) colorectal cancer involving at least two generations and 3) one or more colorectal cancer cases occurring before age 50 years. As with FAP, family members of patients with HNPCC require intensive surveillance. Only about 5% of colorectal cancers occur in these extremely high risk genetic disorders.

There are also patients with genetic family cancer syndromes that may include several different types of cancer and not just colorectal cancer. Again, the tip off to a possibility of hereditary non-site-specific family cancer syndrome includes several family members with cancer over two or more generations. The cancers that tend to be included are, in addition to colorectal cancer, other gastrointestinal cancers, female genital cancer, breast cancer and melanoma.

Approximately 10-15% of patients with colorectal cancer will have a first degree relative who has had the disease but does not have a family history consistent with FAP or HNPCC. People with a single first degree relative with colorectal cancer are at less risk compared to those with FAP or HNPCC. However, they are twice as likely to develop colorectal cancer compared to the general population and the risk is greater if their relative was diagnosed with cancer before the age of 45.

Patients who have inflammatory bowel disease are also at increased risk to develop colorectal cancer. These are diseases of chronic inflammation of the colon. The two broad categories are Crohn’s disease and ulcerative colitis with ulcerative colitis being the greater risk. In addition, the extent of the colon involved and the duration of the disease are major determinants of risk.



Symptoms

The warning symptoms of colorectal cancer are varied (Table 2). These symptoms can be caused by a variety of other problems including ulcers, inflamed colon, hemorrhoids or intestinal spasm. However, if people experience any of these symptoms they should see their doctor.

I want to stress that the whole goal of colorectal cancer screening is to find cancers and precancerous polyps before they cause any symptoms. If cancers are allowed to grow large enough to cause symptoms, they are much less likely to be curable than if they are found in an asymptomatic state during a screening evaluation.



COLORECTAL CANCER PREVENTION

Primary Prevention


Primary prevention involves activities that prevent the development of cancers or precancerous conditions. While that is not really the focus of this review, I feel it imperative to make some comment about lifestyle modifications that may have a positive impact on health.

Diet modification appears to be the single biggest thing that all of us can do to decrease our chance of developing colorectal cancer. There is good information that diets that are high in fruits and vegetables may help decrease the risk of development of colorectal cancer. It appears that antioxidants in these foods are the main protector and so some authorities recommend vitamin supplementation. There is no data to support megavitamin therapy at this point. Physicians have long promoted high fiber diets. Clearly fiber is beneficial for intestinal function and decreases the risk of development of diverticulosis and symptomatic hemorrhoids. Certain types of fiber (soluble) such as oats may also help decrease cholesterol. However, the most recent data does not strongly support the fact that high fiber alone significantly decreases the risk of colon cancer. Diets that are high in fiber may help decrease colorectal cancer because they are also high in fruits and vegetables, and low in foods that may be harmful such as charbroiled and fatty foods. (Obesity alone is a risk factor for colorectal cancer.) These high fiber diets may also be helpful because they allow waste to travel more quickly through the body so that potentially carcinogenic chemicals have less contact time with the colon.

Recent data also supports the concept that diets that are high in calcium and folic acid are beneficial. Women particularly are in need of calcium supplementation for prevention of osteoporosis so clearly diets that are high in calcium are to be recommended except in a few patients with specific medical problems such as kidney stones. A diet that includes 1 mg of folic acid is also recommended.

The area of greatest controversy involves taking aspirin or one of the non steroidal ant-inflammatories (NSAIDs),  while there is data to suggest taking aspirin on a regular basis may decrease the risk of development of colon polyps. Because this data is not yet clear and because taking aspirin or NSAIDs carries certain risks including inducing ulcer disease and possible gastrointestinal bleeding, it is not recommended that aspirin be taken for colon cancer prevention.


Secondary Prevention

Secondary prevention involves activities that detect and treat precancerous lesions or early cancers and thus change the natural history of the disease resulting in less illness and fewer deaths. Screening involves performing tests to detect these lesions in average risk individuals. Surveillance involves testing patients who are at high risk. This is a semantic point and I will use the term screening generically to cover both screening and surveillance.

Screening

There are a variety of tests that can be utilized for colon cancer screening and before talking about the recommendations for implementing the tests, I think it is important to discuss each of the specific tests (Table 3).

Digital rectal examination refers to inspection and palpation of the anal canal and lower rectum by the insertion of a gloved finger by the examining clinician.

Fecal occult blood testing (FOBT) refers to the chemical testing of stool samples for microscopic (nonvisible) amounts of blood. Up to two thirds of patients with colon cancer will have a positive test. The medical studies used the brand name Hemoccult method and so this term is frequently used interchangeably with FOBT although other name brands of this test are available and other methods are now in development to test for occult blood. To guarantee the maximum benefits of this test, a specific protocol needs to be utilized (Table 4). Most people are initially turned off by this unaesthetic test. If FOBT tests are simply handed to patients without being told the importance of this test or being instructed on the proper method to collect samples, as few as 10% will actually follow through on testing. However, with the proper instruction, up to 90% of patients will properly complete the test. If any one of the six samples test positive for occult blood, total colon evaluation with colonoscopy is indicated. If the testing was done in a less than suboptimal situation (the diet instructions were not followed or took aspirin, etc.) the positive test cannot be ignored or "written off".

Flexible sigmoidoscopy refers to the direct visual examination of the lower third to half of the colorectum by a trained examiner using a flexible endoscope. Approximately 50-75% of colon cancers are within reach of this instrument. The only preparation for this test is a simple enema or laxative. The procedure is done as an outpatient without sedation and usually takes five minutes or less. During the examination, there is a nearly constant sensation of the urge to have a bowel movement because of the air that is inflated so that the colon can be optimally visualized. In addition, some mild to moderate cramping may be experienced but this is usually very transient. This newer technology allows for a longer length of colon to be examined with much less discomfort compared to the older technique of proctoscopy that used a rigid tube. Unfortunately, flexible sigmoidoscopy unfairly carries the stigma of patient discomfort that was associated with proctoscopy. For this reason and because of concern about undergoing an "embarrassing" examination, many patients are reluctant to follow their physician’s recommendation to have this test performed. Unfortunately, some physicians hesitate to recommend this potentially life-saving procedure for their patients.

Total colon examination traditionally refers to either of two procedures carried out by a trained examiner after a satisfactory cleansing of the entire colorectum. One procedure is colonoscopy, a direct visual examination of the entire colorectum using a colonoscope. This endoscopic instrument shares the technology of the flexible sigmoidoscope but is longer. This procedure is done with intravenous medications (conscious sedation) so that most patients are very comfortable and, frequently do not remember undergoing the examination. However, because of the sedation, patients cannot drive or do anything that requires coordination for the remainder of the day. Hence, nearly a whole day needs to be committed to this procedure. The other procedure is a barium enema, an x-ray examination of the entire colorectum done by instilling a liquid called barium (single contrast barium enema-SCBE) or barium and air (double contrast barium enema-DCBE) to examine the contours of the colon. While there is some debate, double contrast barium enema is generally accepted as being the more accurate of the two x-ray options and is the preferred x-ray method of the American Cancer Society. These examinations are more uncomfortable (because it is done without sedation) than colonoscopy but are still quite tolerable with most patients describing a cramping like sensation similar to that associated with having an episode of diarrhea. The examination takes less than 30 minutes and since no sedation is involved, patients can return to normal activities immediately after the test.

There are advantages and disadvantages for both the endoscopic and x-ray approaches. Colonoscopy is more sensitive (more likely to find a polyp or cancer if present). About 95-98% of colon cancers will be detected by colonoscopy and 80-95% by barium enema. Colonoscopy also has the potential of treating disease. Most polyps that are found can be removed by "cutting" them out with wire lassos passed through the colonoscope, avoiding the need for a major operation. However, colonoscopy is more involved, primarily because of the sedation and requires more of a patient’s time. In addition, while relatively safe, colonoscopy is of higher risk than barium enema. The newest total colon exam is virtual colonoscopy. This is actually a radiographic procedure that uses magnetic resonance imaging (MRI). While virtual colonoscopy appears to be more sensitive than barium enema it is still somewhat less accurate than colonoscopy and does not have any therapeutic potential. However, because of its low risk, this new technology will most likely have a major role in screening/surveillance in the future. Its appropriate utilization has not yet been determined.


Screening Guidelines

The most recent recommendations of the American Cancer Society (ACS) for screening and surveillance for colorectal polyps and cancer are reviewed in Table 5. The recommendation for average risk patients changed significantly when these new recommendations were released in 1997. Previously, only FOBT and sigmoidoscopy were recommended. For the first time, the alternatives of total colon examination were offered. The recommendations for moderate and high risk are outlined. As I mentioned earlier, screening refers to testing done in average risk patients, while surveillance refers to evaluation of higher risk patients. Most insurance companies do not cover screening but do cover surveillance for certain indications. I will talk more about this when I review cost effectiveness issues.

However, beginning in January of 1998 Medicare did initiate coverage for screening for average risk patients as well as surveillance for higher risk patients. The recommendations for screening/surveillance for Medicare recipients (Table 6) is somewhat different but in large part parallel the recommendations of the American Cancer Society. This important additional benefit became available only after years of intensive lobbying initiated by healthcare professionals.


IS IT WORTHWHILE?

As I mentioned earlier, studies have shown that if all Americans underwent the tests recommended by the standard recommendations of the American Cancer Society, we would decrease the risk of dying from colon cancer by at least 50%. Many fewer people would ever develop colon cancer because they would have precancerous polyps identified and removed before cancer developed. Many more patients would have curable cancers since cancers found in response to screening tests are much more likely to be "early" cancers and more likely to be cured by surgery compared to those that are found in response to evaluation of symptoms.

In addition to saving lives and improving the quality of life, implementation of colon cancer screening would also save healthcare dollars. While it may seem intuitive, it took scientific study to prove the fact that it actually costs less to screen people and to treat precancerous and early cancers than it does to wait for patients to develop symptoms before doing any testing. Another way to look at this question of cost effectiveness of screening would be to compare the cost of screening for colon cancer with the cost for screening for other diseases. One study suggests that standard screening would cost approximately $43,000 per year of life gained. A more recent study concluded that screening with colonoscopy every 10 years would cost even less, $6,600 per year of life gained. This compares favorably with annual breast cancer screening with mammography (approximately $22,000-$35,000 per year of life gained) and cervical cancer screening ($250,000 per year of life gained). Moreover, colon cancer screening clearly is more cost effective than many of the life saving interventions that we take for granted in our daily lives. In a study done by the Harvard Center for Risk Analysis, among several lifestyle interventions, only the mandatory wearing of motorcycle helmets would be more cost effective than colon cancer screening (Table 7).

If colon cancer screening saves lives, improves quality of life and saves healthcare dollars, why do so few private insurance carriers cover screening? A generous response would be it is because they are ignorant of the facts. One might propose a more cynical explanation. Since a large number of people change their healthcare coverage on a fairly regular basis it is conceivable that some carriers might consider playing the numbers game. They could save the dollars spent on screening now and hope that by the time someone develops the symptomatic cancer they will either be under Medicare coverage or at very least have switched to another carrier who will need to pick up the tab for treatment of the symptomatic, advanced cancer.



WHAT SHOULD I DO?

First, I would ask that you determine your risk level from the information supplied and be aware of the recommendations for screening that apply to you. Next, initiate the appropriate screening program with your physician if you have not already done so. Help yourself by eating healthy.

For those of you who have insurance that does not cover screening, write to your insurer and ask them to justify their actions. Senator Edward Kennedy has submitted a bill (S. 1044) that would require private insurance companies supply the same level of service as is now afforded to Medicare recipients. A parallel bill (H.R.1816) has been submitted to the House of Representatives. I would suggest that you write or call your representatives encouraging them to support this legislation so that your healthcare premiums are better used to afford you good health. If you do not have a physician and want to participate in a colon cancer screening program please call one of my nurse assistants, Gina or Dana at (901) 747-3630 for further information.



Bibliography
Byers T. et al. American Cancer Society guidelines for screening and surveillance for early detection of colorectal polyps and cancer: update 1997. CA- A Cancer Journal for Clinicians 1997; 47:154-160.
Guide to Preventive Services. 2nd ed. Report of the U.S. Preventive Services Task Force. Washington, D.C.: Department of Health and Human Services, 1995.
Levin B, Bond JH. Colorectal cancer screening: Recommendations of the U.S. Preventive Services Task Force. Gastroenterology 1996;111:1381-1384. (editorial)
Winawer SJ, et al. Colorectal cancer screening: Clinical guidelines and rationale. Gastroenterology 1997;112:594-642.
Ransohoff DF, Lang CA, et al. Suggested technique for fecal occult blood testing and interpretation in colorectal screening. Ann Intern Med 1997;126:808-822.
Medicare Bulletin-GR98-2 March/April 1998 pg 5-6.


Dr. Cattau is a member of the Memphis Gastroenterology Group and is a Clinical Professor of Medicine at the University of Tennessee.

Dr. Cattau received his medical degree from the University of North Carolina and did his medical training in the U.S. Navy including a fellowship in gastroenterology at the National Naval Medical Center in Bethesda Maryland where he subsequently became Chief of Gastroenterology. In that position, he attended his most famous patient, President Ronald Reagan. He diagnosed President Reagan’s colon cancer by colonoscopy that was prompted by a positive screening FOBT. This cancer was subsequently cured by surgery. Immediately prior to moving to Memphis, Dr. Cattau was Associate Professor of Medicine on the fulltime faculty at Georgetown University Hospital in Washington, D.C. and was the Clinical Director of Endoscopy at the National Institutes of Health.

His special interests include colon cancer screening, therapeutic endoscopy and staging of colon cancers with the newest technology available, endoscopic ultrasonography.



TABLES

TABLE 1: High Risk Factors for the Development of Colorectal Cancer

•  History of previous colon polyp or colorectal cancer.
•  Family history of hereditary polyposis syndromes.
•  Family history of hereditary nonpolyposis syndromes.
•  Family history of colorectal cancer.
•  Inflammatory bowel disease.

TABLE 2: Symptoms of Colorectal Cancer

•  A change in bowel habits.
•  Diarrhea or constipation.
•  Blood in or on the stool (either bright red or very dark in color).
•  Stools that are narrower than usual.
•  General stomach discomfort (bloating, fullness and/or cramps).
•  Frequent gas pains.
•  A feeling that the bowel does not empty completely.
•  Weight loss of unknown reason.
•  Constant tiredness.

TABLE 3: Colorectal Cancer Screening Tests

•  Digital rectal exam.
•  Fecal occult blood test.
•  Flexible sigmoidoscopy
•  Total colon examination-
•  Colonoscopy
•  Barium Enema
•  Virtual Colonoscopy.

TABLE 4: Proper Performance of the Fecal Occult Blood Test

For 3 days before and during testing, patients should avoid:

•  Rare red meat
•  Peroxidase-containing vegetables/fruit (e.g., broccoli, turnip, cantaloupe, cauliflower, radish)
•  The following medications:
•  Iron supplements
•  Vitamin C
•  Aspirin
•  Nonsteroidal anti-inflammatory drugs

Two samples of each of the three consecutive stools should be tested. (It is proper to sample areas of obvious blood.)

Slides should be developed within 4-6 days.

TABLE 6: Medicare guidelines for

SCREENING AND SURVEILLANCE FOR EARLY DETECTION OF COLORECTAL POLYPS AND CANCER

Risk Category

Recommendation

Age to Begin

Interval

AVERAGE RISK      

All people 50 years or older
who are not in the categories below.

FOBT and Flexible Sigmoidoscopy
and/or Barium Enema.

Age 50

FOBT every year and either
Flexible Sigmoidoscopy or Barium Enema every 48 months.

HIGH RISK

Close relative (sibling, parent
or child) with colorectal cancer or adenomatous polyposis.

Colonoscopy

N.A.

Every 24 months.

Family history of familial adenomatous polyposis.

Family history of hereditary nonpolyposis colorectal cancer.

Personal history of adenomatous polyposis.

Personal history of colorectal cancer.

Inflammatory bowel disease (Crohn’s Disease, Ulcerative Colitis).

 

TABLE 7 Cost-Effectiveness of Lifestyle Interventions (Cost/Year Life Saved)

•  Mandatory Motorcycle helmets $2,000
•  Colorectal Cancer Screening $25,000
•  Breast Cancer $35,000
•  Dual Airbags in Cars $120,000
•  Smoke Detectors in Homes $210,000
•  Seat Belts in School Buses $2,800,000

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