++
Colorectal cancer is ideal for screening because it is a common disease that is fatal in almost 50% of cases and yet is curable if detected at an earlier stage. Furthermore, most cases arise from benign adenomatous or serrated polyps that progress over many years to cancer, and removal of these polyps has been shown to prevent the majority of cancers. Colorectal cancer screening is endorsed by the USPSTF, 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 screening is cost-effective. It is important for primary care providers to understand the relative merits of various options and to discuss them with their patients.
++
Less than 65% of adults over age 50 are up-to-date with colorectal screening. Discussion and encouragement by the primary care provider are the most important factors in achieving patient compliance with screening programs. A 2018 Kaiser Permanente study reported increased participation to 82.5% through an organized screening program. Currently in the United States, the two most widely used strategies are colonoscopy every 10 years or fecal immunochemical testing (FIT) annually.
++
Recommendations for screening from the 2016 USPSTF and 2008 US Multi-Society Task Force (USMSTF) are listed in Table 39–6. Screening is recommended for all men and women 50 through 75 years of age who are at average risk for cancer. Many guidelines recommend screening for African Americans and Alaska Natives beginning at age 45. In 2018, the American Cancer Society provided a qualified recommendation for starting screening at age 45 for average-risk adults; however, other agencies do not feel that available evidence yet supports this recommendation. 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. Although routine screening is not recommended in adults above age 75, it may be considered on a case-by-case basis in adults age 76 through 85 years who have excellent health and functional status. In 2017, the USMSTF issued revised, simplified recommendations in which screening tests were placed into three tiers (Table 39–7). For average-risk patients, colonoscopy every 10 years or FIT testing is preferred (Tier 1). Tier 2 tests (CT colonography every 5 years, flexible sigmoidoscopy every 5 years, or fecal FIT-fecal DNA testing every 3 years) and Tier 3 tests (colon capsule every 5 years) may be offered but are considered less suitable due to various disadvantages (discussed below).
++
++
++
Patients with first-degree relatives with colorectal neoplasms (cancer or adenomatous polyps) are at increased risk. Therefore, most guidelines recommend initiating screening at age 40–50 years (or 10 years younger than the familial diagnosis) in individuals with first-degree relatives with colorectal cancer or with advanced adenomas. Recommendations for screening in families with inherited cancer syndromes or inflammatory bowel disease are provided in Chapter 15. For patients at average risk for colorectal cancer, the recommendations of the USPSTF and USMSTF are discussed below.
++
Screening tests may be classified into two broad categories: stool-based tests and examinations that visualize the structure of the colon by direct endoscopic inspection or radiographic imaging.
+++
1. Fecal occult blood test
++
Most colorectal cancers and some large adenomas result in increased chronic blood loss. A variety of tests for fecal occult blood are commercially available that have varying sensitivities and specificities for colorectal neoplasia. These include guaiac-based fecal occult blood tests (gFOBT) (eg, Hemoccult I and II and Hemoccult SENSA) that detect the pseudoperoxidase activity of heme or hemoglobin and FITs that detect human globin. In clinical trials, FITs have proven superior to gFOBT in sensitivity for detection of colorectal cancer and advanced adenomas with similar specificity. Because FITs are not affected by diet or medications and have superior accuracy, the USMSTF now recommends their use instead of gFOBT.
++
When gFOBT is administered to the general population as part of a screening program, 2–6% of tests are positive. Of those with positive tests, 5–18% have colorectal cancer that is more likely to be at an earlier stage (stage I or II). For optimal detection, annual testing is required. In a meta-analysis of four large, prospective, longitudinal studies, annual or biennial screening with Hemoccult I or Hemoccult II reduced mortality from colorectal cancer by 25% among those who were compliant with regular testing.
++
Several FIT kits are commercially available. These tests are highly specific for detecting human globin and therefore eliminate the need for pretest dietary restrictions. In 19 clinical studies, the pooled sensitivity and specificity of FIT for colorectal cancer in average-risk patients were 79% and 94%, respectively. The optimal interval (yearly or every 2 years) and number of stool samples (one or two) required for optimal FIT testing is as yet undetermined. Three randomized controlled trials comparing one-time colonoscopy with FIT testing for colorectal cancer screening are ongoing. Currently, annual testing of a single stool sample is recommended.
++
FIT testing is the preferred option for population-based screening in various European and Australian programs. In the United States, it is offered as the preferred option by many healthcare plans. For healthcare systems in which screening colonoscopy is readily available, FIT is a suitable option for patients seeking a noninvasive screening test who are willing to undertake annual fecal testing. Patients with a positive FIT test must undergo further evaluation with colonoscopy.
+++
2. Multitarget DNA assay
++
Stool DNA tests measure a variety of mutated genes and methylated gene markers from exfoliated tumor cells. A newer-generation assay (Cologuard) combines a fecal DNA panel with a FIT. In a prospective comparative trial conducted in persons at average risk for colorectal cancer undergoing colonoscopy, the sensitivity for colorectal cancer for Cologuard was 92.3% vs 73.8% for FIT alone and the sensitivity for adenomas larger than 1 cm or serrated polyps for Cologuard was 42.4% vs 23.8% for FIT alone. A positive stool DNA test requires colonoscopy evaluation. Compared with FIT testing alone, FIT-fecal DNA testing has disadvantages including higher cost, lower specificity, lower cost-effectiveness, and cumbersome requirements for stool collection and mailing. Hence, the 2017 USMSTF relegated it to Tier 2, noting that it may be recommended in patients age 50–65 years who seek a noninvasive test with high-sensitivity, due to acceptable specificity in this age group.
+++
B. Endoscopic Examinations of the Colon
++
Colonoscopy permits examination of the entire colon. In addition to detecting early cancers, colonoscopy allows removal of adenomatous polyps by biopsy or polypectomy, which is believed to reduce the risk of subsequent cancer. Over the past decade, there has been a dramatic increase in screening colonoscopy, with over 60% of US adults screened in the past 10 years. In asymptomatic individuals between 50 and 75 years of age undergoing screening colonoscopy, the prevalence of advanced colonic neoplasia is 4–11% and of colon cancer is 0.1–1%.
++
Although colonoscopy is believed to be the most sensitive test for detecting adenomas and cancer, it has several disadvantages. To allow adequate visualization of the entire colonic mucosa, it requires thorough bowel cleansing the evening and morning prior to the examination. To alleviate discomfort during the procedure, intravenous sedation is used for most patients, necessitating a companion to transport the patient home post-procedure. Serious complications occur uncommonly; they include perforation (0.1%), bleeding (0.25%), and death (2.9/100,000).
++
The skill of the operator has a major impact upon the quality of the colonoscopy examination. 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 polyps and early cancers that were overlooked during the colonoscopy. Studies of back-to-back colonoscopies confirm that endoscopists overlook 6–12% of polyps greater than 1 cm in size and up to 25% of smaller adenomas. Polyps that are small, flat, or located behind folds are easily missed, especially if the bowel preparation is poor. Population-based case-control and cohort studies suggest that colonoscopy is associated with greater reduction in colorectal cancer incidence and mortality in the distal colon (80%) than the proximal colon (40–60%). This may be attributable to incomplete examination of the proximal colon, and differences between the proximal and distal colon that include worse bowel preparation, suboptimal colonoscopic technique, and a higher prevalence of serrated polyps and flat adenomas. The latter are more common than previously recognized, are more likely to contain advanced pathology, and are more difficult to identify than raised (sessile or pedunculated) polyps. To optimize diagnostic accuracy as well as patient safety and comfort, colonoscopy should be performed after optimal bowel preparation by a well-trained endoscopist who spends sufficient time (at least 7 minutes) carefully examining the colon (especially the proximal colon) while withdrawing the endoscope.
+++
2. 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, it is performed by a nurse-specialist or physician assistant. Adenomatous polyps are identified in 10–20% and colorectal cancers in 1% of patients. The finding at sigmoidoscopy of an adenomatous polyp in the distal colon increases the likelihood at least twofold that an advanced neoplasm is present in the proximal colon. Therefore, patients with an adenomatous polyp of any size found during screening sigmoidoscopy should subsequently undergo colonoscopy to evaluate the proximal colon. A 2012 US study of almost 155,000 participants randomized to sigmoidoscopy screening or usual care between 1993 and 2001 reported a 50% reduction in distal colorectal cancer mortality in the sigmoidoscopy group after 11 years median follow-up.
++
The chief disadvantage of screening with flexible sigmoidoscopy is that it requires some bowel cleansing, it may be associated with some discomfort (since intravenous sedation is not used), and it does not examine the proximal colon. The prevalence of proximal versus distal neoplasia is higher in persons older than age 65 years, in African Americans, and in women. For these reasons, the 2017 USMSTF recommendations have placed flexible sigmoidoscopy among Tier 2 tests. If chosen, flexible sigmoidoscopy should be performed every 5–10 years.
+++
C. Radiographic and Other Imaging of the Colon
++
Using helical CT with computer-assisted image reconstruction, two- and three-dimensional views can be generated of the colon lumen that simulate the view of colonoscopy (virtual colonoscopy). CT colonography requires a similar bowel cleansing regimen as colonoscopy as well as insufflation of air into the colon through a rectal tube, which may be associated with discomfort. Nonetheless, this examination is performed rapidly and requires no sedation or intravenous contrast. Several large studies have compared the accuracy of virtual colonoscopy with colonoscopy for colorectal screening. Using current imaging software with multidetector helical scanners, the sensitivity is greater than 95% for the detection of cancer and greater than 84–92% for the detection of polyps 10 mm or larger. CT colonography is less sensitive than colonoscopy for the detection of polyps smaller than 1 cm, flat adenomas, and serrated polyps.
++
Patients undergoing screening with CT colonography should be managed appropriately. If no polyps are found, the interval for repeat screening examination is uncertain; however, 5 years may be reasonable. All patients with polyps 10 mm or larger should be referred for colonoscopy with polypectomy because of the high prevalence (30%) of advanced pathology (cancer, high-grade dysplasia, or villous features) within these polyps. The optimal management of patients with polyps less than 10 mm in size is controversial. The USMSTF currently recommends that colonoscopy with polypectomy be offered to patients with one or more 6–9 mm polyps. Patients who refuse or who have increased risk of carcinoma should undergo surveillance CT colonography in 3–5 years. At the present time, there is no consensus on the management of patients with polyps smaller than 6 mm; however, some radiologists choose not even to report these findings.
++
The chief disadvantages of CT colonography are the need for a bowel preparation, limited availability in many health care systems, a possible increased risk of neoplasia due to radiation exposure, and the potential for finding incidental extracolonic findings that may lead to further evaluations. The 2017 USMSTF has therefore classified this as a Tier 2 screening option (Table 39–7). CT colonography is an excellent screening option in patients who do not wish to undergo or are unsuitable for colonoscopy and in patients in whom colonoscopy could not be completed.
+++
2. Capsule colonoscopy
++
Imaging of the colon can be accomplished by oral ingestion of a capsule that captures video images of the colon. Compared with colonoscopy, the colon capsule has reduced sensitivity for polyps greater than 6 mm (64% vs 84%) and for colorectal cancers (74% vs 100%). At present, it is approved by the FDA for evaluation in patients who are not suitable candidates for colonoscopy or in whom colonoscopy could not evaluate the proximal colon. In addition to its suboptimal sensitivity for neoplasia, the main disadvantages of capsule colonoscopy are its cost, need for extensive bowel preparation, lack of reimbursement by most insurance carriers, and small risk of small bowel obstruction. For these reasons, the 2017 USMSTF recommendations classified it a Tier 3 screening test, suitable for highly selected patients (Table 39–7).
++
3. Barium enema—Double-contrast barium enema was previously used as a screening technique because it was widely available, relatively inexpensive, and safe. However, compared to CT colonography, it is more time-consuming and difficult to perform, less comfortable, and less accurate. It can no longer be recommended for routine screening.