Colorectal cancer is ideal for screening because it is a common disease affecting 6% of men and women that is fatal in almost 50% of cases yet is curable if detected at an earlier stage. Furthermore, the vast majority of cases arise from benign adenomas that progress over many years to cancer, and removal of adenomas has been shown to prevent the vast majority of cancers. Colorectal cancer screening has now been endorsed by the United States Preventive Services Task Force, the Agency for Health Care Policy and Research, the American Cancer Society, and every professional gastroenterology and colorectal surgery society. Although there is continued debate about the optimal cost-effective means of providing population screening, there is unanimous consent that screening of some kind should be offered to every patient over the age of 50 years. Several analyses suggest that the cost of screening is approximately $25,000 per year of life saved for all recommended screening strategies, which is well below the range of $40,000-$50,000 per year generally considered to be cost-effective.

A number of options for screening are available and reimbursed by third-party payers and by Medicare.  Patients with first-degree relatives with colorectal cancer are at increased risk, and for these individuals more intensive screening recommendations are recommended.

The advantages and disadvantages of the various options are discussed below. It is important for primary care providers to understand the relative merits of various options and to discuss them with their patients. Despite growing awareness of the importance of screening on the part of medical professionals and the public, less than 50% of patients have undergone screening of any kind. Discussion and encouragement by the primary care provider are the most important factors in achieving patient compliance with screening programs. The potential for harm from screening must be weighed against the likelihood of benefit, especially in elderly patients with comorbid illnesses and shorter life expectancy.

A. Fecal Occult Blood Test or Multitarget DNA Assay

Most colorectal cancers and some large adenomas result in increased chronic blood loss that may be detectable. A variety of tests have been developed that have varying sensitivities for fecal occult blood, some of which are in clinical testing. A guaiac-based test (Hemoccult II) has undergone the most extensive testing and has had the greatest clinical use. Two slides must be prepared from three consecutive bowel movements. To reduce the likelihood of false-positive tests, patients should abstain from aspirin (in doses greater than 325 mg/d), NSAIDs, red meat, poultry, fish, and vegetables with peroxide activity (turnips, horseradish) for 72 hours. Vitamin C may cause a false-negative test. Slides should be developed within 7 days after preparation. The World Health Organization recently endorsed another guaiac test for FOBT, Hemoccult Sensa, because it has higher sensitivity than the Hemoccult II test; however, data from large clinical trials with this test are lacking.

When FOBT is administered to the general population as part of a screening program, 2-6% of tests are positive. Patients with positive tests should undergo colonoscopy accompanied by removal of any polyps identified. If colonoscopy reveals no colorectal neoplasm, further screening for colorectal cancer can be deferred for 10 years. Of those with positive tests, 5-18% have colorectal cancer, more likely to be at an earlier stage (Dukes A or B). Adenomatous polyps are identified in 25-50% of patients with positive tests. Finding these polyps is somewhat fortuitous since most are less than 1 cm in size and unlikely to cause occult bleeding. The estimated sensitivity of a one-time guaiac-based FOBT for colorectal cancer is only 13%; however, sensitivity is increased in patients who undergo annual or biannual testing. In several large prospective studies, FOBT has been demonstrated to reduce mortality from colorectal cancer by 30-40% among those who are compliant with regular testing. An immunochemical FOBT that detects human globin is available. The test is positive in 3-6% of asymptomatic patients and has a sensitivity of 65% for detection of colorectal cancer and 28% for all advanced neoplasms.

A fecal DNA assay (Pre-Gen Plus) is commercially available for screening for colorectal neoplasia. The test analyzes fecal DNA for point mutations in the APC, K-ras, and p53 genes, microsatellite instability, and a marker of abnormal apoptosis. However, in a recent study performed in a large asymptomatic screening population, the fecal DNA panel detected only one-half of cancers and only 18% of all advanced neoplasms.

The low sensitivity of FOBT and DNA tests for advanced neoplasia makes them a less attractive choice for population-based screening than endoscopic or radiographic tests. At present, they are most suitable in settings where health care resources are limited or in patients who desire a noninvasive method of screening. If FOBT screening is to be used, immunochemical tests may be preferred.

B. Flexible Sigmoidoscopy

Use of a 60-cm flexible sigmoidoscope permits visualization of the rectosigmoid and descending colon. It requires no sedation and in many centers is performed by a nurse specialist or physician’s assistant. Adenomatous polyps are identified in 10-20% and colorectal cancers in 1% of patients. (For management of adenomatous polyps identified at sigmoidoscopy, see Chapter 14). Case-control studies suggest that screening sigmoidoscopy programs lead to a 60% reduction in colorectal cancer mortality. The risk of serious complications (perforation) associated with flexible sigmoidoscopy is less than 1:10,000 patients.

However, approximately 50% of advanced neoplasms (cancer, adenomas ? 1 cm in size, polyps with villous histology, or high-grade dysplasia) are proximal to the splenic flexure, ie, above the reach of a flexible sigmoidoscopic examination. Up to 60% of such patients do not have an adenomatous polyp distal to the splenic flexure at sigmoidoscopy. Therefore, if patients found on screening sigmoidoscopy to have an adenoma of any size subsequently undergo colonoscopy, approximately 70% of all advanced colonic neoplasms will be identified; however, using such a strategy means that 30% of patients with advanced colonic neoplasia located only in the proximal colon will be overlooked.

C. Screening Colonoscopy

Colonoscopy permits examination of the entire colon. For this reason, screening colonoscopy is the preferred screening test in patients deemed to be at higher risk due to a positive family history of colorectal cancer. Colonoscopy has been advocated by the American College of Gastroenterology as the preferred screening modality in average-risk patients as well. In asymptomatic individuals between 50 and 75 years of age undergoing screening colonoscopy, the prevalence of advanced neoplasia is 6-11% and of cancer is 1%. To alleviate discomfort, intravenous sedation is used for most patients. The incidence of serious complications after colonoscopy (perforation, bleeding, cardiopulmonary events) is 0.1%. Although colonoscopy is believed to be the most sensitive test for detecting adenomas and cancer, it is not infallible. In several studies, the rate of colorectal cancer within 3 years of a screening colonoscopy was 0.7-0.9%, ie, approximately 1 in 110 patients. This may be attributable to neoplasms that were overlooked during colonoscopy or undergo rapid progression to cancer after the colonoscopy. Studies of back-to-back colonoscopies confirm that endoscopists overlook 6-12% of polyps > 1 cm and up to 25% of smaller adenomas. Polyps that are small, flat, or located behind folds are easily missed. Therefore, colonoscopy should be performed after optimal bowel preparation by a well-trained endoscopist who spends at least 6 minutes examining the colon while withdrawing the endoscope.

D. Double Contrast Barium Enema

Like colonoscopy, barium enema permits examination of the entire colon. Barium enema has been an attractive screening technique because it was widely available, relatively inexpensive, and safe. However, it is being rapidly supplanted by colonoscopy and CT colonography. A recent multicenter trial demonstrated that the sensitivity of barium enema is only 50% for polyps ? 1 cm and 55-85% for early-stage cancers when compared with colonoscopy. At present, barium enema may be recommended when screening of the entire colon is desired and the patient is unable or unwilling to undergo colonoscopy, and expertise in CT colonography is unavailable.

E. CT Colonography (Virtual Colonoscopy)

Using computer-assisted image reconstruction and rapid helical CT, two- and three-dimensional views can be generated of the colon lumen that simulate the view of colonoscopy. This technique is performed rapidly, requires no sedation or intravenous contrast, and has minimal risk except for radiation exposure. At this time, it requires a similar bowel cleansing regimen as colonoscopy as well as the insufflation of air into the colon through a rectal tube, which may be associated with discomfort. In several recent large studies, the accuracy of virtual colonoscopy compared with colonoscopy has been assessed for the screening of colorectal neoplasia in asymptomatic screening populations. In several studies, the sensitivity of virtual colonoscopy for the detection of polyps larger than 8-10 mm is > 90%; however, other studies report sensitivity of only 50-60%. Abnormalities identified on CT imaging require assessment by colonoscopy. Although most professional guidelines do not yet endorse virtual colonoscopy for routine colorectal screening, it is a reasonable alternative for patients in whom screening of the entire colon is desired but who are unable or unwilling to undergo colonoscopy.

Rebecca A. Barnetson and Malcolm G. Dunlop
Colon Cancer Genetics Group, University of Edinburgh, School of Molecular and Clinical Medicine and MRC Human Genetics Unit, Western General Hospital, Edinburgh, U.K.

References