GI Consult: Colorectal Cancer

Review the latest findings on the accuracy and cost-effectiveness of the primary colorectal cancer screening tools—fecal occult blood tests, flexible sigmoidoscopy, double-contrast barium enema, and colonoscopy—used alone or in combination.

By John H. Bond, MD

Why is screening for colorectal cancer important?

Colorectal cancer is the second most common cancer killer of Americans, after lung cancer. Each year, there are approximately 140,000 new cases in the United States, and the disease causes about 56,000 deaths. It is the only major malignancy that afflicts men and women almost equally. Tragically, this cancer that causes so much pain, suffering, loss of life, and expenditure of medical resources is highly curable and even preventable if it detected early through screening.

When colorectal cancer is diagnosed, the likelihood of long-term survival depends mainly on the anatomic stage of the disease found at surgery. Before symptoms develop, most cancers are still localized to the bowel (Dukes' stage A or B) and five-year survival exceeds 80%. By the time symptoms occur, however, most colorectal cancers have spread outside the bowel to lymph nodes (Dukes' stage C) or beyond, and the chance of survival decreases by more than half.

A primary objective of screening, therefore, is to detect these cancers before symptoms appear, when there is an excellent chance of surgical cure. A second important objective is to find and resect premalignant benign adenomatous polyps (or adenomas). It is now believed that more than 95% of colorectal cancers in Western countries develop from these adenomas, which grow very slowly over many years before they turn cancerous. Most of these polyps are silent or asymptomatic lesions that can be detected only through screening.

There is now strong scientific evidence that finding and resecting advanced adenomatous polyps before they turn malignant will reduce the subsequent incidence of colorectal cancer by up to 90%. Advanced adenomas are defined as those that are more than 1 cm in diameter or that contain villous tissue or high-grade dysplasia. These are the ones likely to become malignant if they are not resected.
 

Who should be screened for colorectal cancer?

Three current evidence-based guidelines recommend that all asymptomatic, average-risk men and women should be offered screening for colorectal cancer beginning at age 50, which is when the incidence of the disease starts to accelerate. Some people are at higher risk for the disease because of a family or personal history of colorectal cancer or adenomas or because they have chronic ulcerative colitis or Crohn's colitis. These higher-risk groups may require periodic colonoscopy beginning at a younger age rather than routine screening. People who have symptoms that might be due to colorectal cancer, especially those with rectal bleeding or unexplained iron-deficiency anemia, also may require a definitive work-up, usually with colonoscopy, rather than routine screening.

The guidelines also emphasize that screening should be individualized. In the case of a person of advanced age, for example, or one with a significant concomitant disease, screening should be discontinued because it is no longer likely to be of any benefit.
 

What screening method do the guidelines now recommend?

All three guidelines make the same recommendations for screening average-risk people. Unlike screening for other major cancers, such as breast, cervical, or prostate cancer, they do not recommend a single screening strategy for every person. Rather, the guidelines present a menu of five screening options, each with different advantages and limitations. They stress that any one of the options is appropriate, and they urge physicians and patients to chose one in a joint decision-making process.

The five options include: annual fecal occult blood tests (FOBTs), flexible sigmoidoscopy every five years, a combination of annual FOBTs and flexible sigmoidoscopy every five years, double-contrast barium enema every five years, or colonoscopy every 10 years. The only unacceptable option is not to screen.
 

What are the advantages and limitations of FOBT screening?

The FOBT is the only method of colorectal cancer screening that has been proved effective in randomized, controlled trials. Our study at the University of Minnesota, in which participants were randomized into a screening or control group and those with a positive FOBT underwent colonoscopy, showed that annual screening can reduce mortality from colorectal cancer by more than 40%. By detecting patients with bleeding premalignant polyps, this screening method also reduced the incidence of cancer (that is, prevented cancer from developing) by more than 20%.

Aside from its proven efficacy, other advantages of FOBT screening are that it is widely available, acceptable to patients, and has a very low up-front cost. Limitations include a relatively low sensitivity for smaller polyps and for distal cancers, a substantial number of false-positive screens, and the need for frequent, repetitive screening. Also, when using guaiac-based FOBTs, dietary restrictions that some people find objectionable are recommended.

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Should a screening FOBT be performed on stool specimens obtained by digital rectal examination during a routine physical examination?

When using guaiac-based FOBTs, patients generally collect six stool specimens—two each from three consecutive bowel movements, after following a diet free of red meat, vitamin C, and fruits and vegetables that contain peroxidases. A recent multicenter study showed, however, that a positive FOBT of stool obtained during a digital rectal examination has a similar accuracy and predictive value for detecting colorectal cancer as tests done with spontaneously passed stool. So a positive test is an indication for colonoscopy. However, with this method, false-negative guaiac tests may be more common, since only one stool specimen is tested. Therefore, when a FOBT performed on stool obtained by digital rectal examination is negative, FOBT screening should always be repeated with spontaneously passed stool in the manner described above.
 

What is the recommended evaluation for a patient with a positive screening FOBT?

Colonoscopy is indicated whenever there is a positive FOBT screening test. Studies have shown that colonoscopy is more accurate for diagnosing both cancers and advanced adenomatous polyps than is air-contrast barium enema examination. Furthermore, colonoscopy was used as the diagnostic test in the trials that demonstrated the efficacy of FOBT screening. Colonoscopy also has the obvious advantage of allowing for biopsy of suspicious lesions and resection of most polyps, all at a single sitting with a single bowel preparation.
 

Is flexible sigmoidoscopy an effective screening test? Should it be combined with FOBT screening?

Flexible sigmoidoscopy has a number of important advantages as a screening test. It is generally acceptable to patients, relatively inexpensive, and can be performed safely in a few minutes by well-trained examiners after a simple bowel cleansing preparation. It is highly accurate and can examine most of the left colon, the site of 60% to 70% of colorectal cancers and polyps. Although there are not yet any reported results from randomized trials, case-control studies suggest that flexible sigmoidoscopy will reduce mortality from colorectal cancer within its reach by 60% to 85%. A positive flexible sigmoidoscopy is an indication for colonoscopy to examine and clear the entire colon. The main limitation of flexible sigmoidoscopy is that, when performed alone, it will miss the roughly 25% of colorectal cancers and advanced adenomas located only in the proximal colon, with no distal neoplasm that would lead to full colonoscopy.

Many believe that the combination of annual FOBT screening and flexible sigmoidoscopy every five years is a preferred screening strategy because performing both tests largely corrects the limitations of doing either test alone. Flexible sigmoidoscopy will accurately detect lesions in the high-risk left colon, whereas repetitive FOBT screening will detect most cancers and many advanced adenomas in the proximal colon that flexible sigmoidoscopy would miss.
 

What is the current role of direct screening with barium enema or colonoscopy?

Both of these methods are included in the guidelines as screening options, although at the present time they are supported by indirect evidence only. Barium enema is not used much in the United States for screening purposes and has not been extensively evaluated. It is substantially less accurate for detecting cancers and advanced adenomatous polyps than colonoscopy. Therefore, the guidelines recommend that if barium enema is used for screening, it should be repeated at five-year intervals.

Colonoscopy screening is now the option that seems to be preferred by most gastroenterologists and by an increasing number of average-risk patients. It clearly is the most accurate way to detect curable cancers and advanced adenomas, and it allows for resection of most polyps at the time they are found. Because of its great accuracy and the long natural history of the adenoma-carcinoma sequence, a negative colonoscopy does not have to be repeated for at least 10 years, according to the guidelines. A recent large multicenter trial of screening colonoscopy conducted in the Veterans Affairs hospital system demonstrated that the test can be performed in large numbers of asymptomatic people effectively and safely when done by well-trained, experienced endoscopists.

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What type of screening is recommended for patients with a family history of colorectal cancer or adenomatous polyps?

More than any other major malignancy, colorectal cancer tends to be familial. Studies indicate that 30% or more of colorectal cancers result, in part, from an inherited genetic risk. Therefore, when a patient develops a cancer or an advanced adenoma, it is also important to evaluate other family members. First-degree relatives (parent, sibling, or child) of these patients have an increased risk of getting the disease that is estimated to be two to four times that of the average-risk population. The risk is even higher if the first-degree relative was diagnosed before age 60. Screening guidelines recommend that these close relatives be offered direct colonoscopy surveillance every five years beginning at age 40.
 

Is colorectal cancer screening cost-effective?

A number of mathematical modeling analyses have addressed this question. All have concluded that any of the five recommended options for colorectal cancer screening is highly cost-effective compared with other preventive medical interventions that are well accepted today. Some of these studies suggest that it may be more costly not to screen for this malignancy than to screen. This is because the cost of caring for a patient with advanced colorectal cancer far exceeds the cost of either preventing cancers by finding and removing polyps or of performing surgery for an early-stage, curable cancer. So in addition to the important benefits of preventing pain, suffering, and loss of life from this deadly disease, screening also appears to be a very good economic investment.

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