An average-risk individual is defined as an asymptomatic person without a personal or family history of colonic polyps or cancer. The majority of the general population is considered to be at average risk for CRC. Given that age is the strongest risk factor for the development of CRC and adenomatous polyps, men and women at average risk should be offered screening beginning at age 50 years.
Available screening options for average-risk individuals fall into two broad categories: (1) tests that primarily detect CRC, and (2) those that detect precancerous adenomatous polyps and CRC (Table 22–1). Tests that primarily detect cancer are fecal tests, including guaiac-based and immunochemical occult blood tests, and fecal DNA tests. These modalities provide limited opportunity for prevention because detection of premalignant adenomatous polyps is most often incidental. Tests that detect both adenomatous polyps and cancer include flexible sigmoidoscopy (FS), colonoscopy, double-contrast barium enema (DCBE), and computed tomography colonography (CTC). Because prevention is the primary goal of CRC screening, recent guidelines from the American Cancer Society, the U.S. Multisociety Task Force on Colorectal Cancer, and the American College of Radiology strongly encourage clinicians to offer those tests that are designed to detect both early cancer and adenomatous polyps if resources are available and if patients are willing to undergo an invasive examination. Noninvasive tests must be repeated at regular intervals to be effective, are less likely to prevent CRC than invasive examinations, and, if abnormal, require colonoscopy.
Table 22–1. Testing Options for Asymptomatic Adults Aged 50 Years and Older. ||Download (.pdf)
Table 22–1. Testing Options for Asymptomatic Adults Aged 50 Years and Older.
Tests that detect adenomatous polyps and CRC
- Flexible sigmoidoscopy
- Double-contrast barium enema
- Computed tomography colonography
Tests that primarily detect CRC
- Guaiac-based fecal occult blood testing
- Fecal immunochemical tests
- Stool DNA
Nevertheless, health care providers are encouraged to focus on increasing screening rates through periodic use of any of the recommended modalities. Providers should present their patients with information about the advantages and disadvantages associated with the multiple available screening tests. In turn, patients have the opportunity to select how they wish to be screened based on their own preferences. The rationale for such an approach is that it may increase the likelihood that screening will occur. Even though the currently available screening techniques are not equal in effectiveness, cost, or associated risks, they all have been demonstrated to be cost-effective compared with no screening at all.
Levin B, Lieberman DA, McFarland B, et al. Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multisociety Task Force on Colorectal Cancer, and the American College of Radiology. Gastroenterology.
Smith RA, Mettlin CJ, Davis KJ, et al. American Cancer Society guidelines for the early detection of cancer. CA Cancer J Clin.
Winawer S, Fletcher R, Rex D, et al. Gastrointestinal Consortium Panel. Colorectal cancer screening and surveillance: clinical guidelines and rationale–update based on new evidence. Gastroenterology
Individuals with a personal or family history of adenomatous polyps or CRC are considered to be at intermediate risk for the development of CRC. For these patients, colonoscopy is the recommended screening method. Other conventional screening modalities are not typically recommended in this setting.
Personal History of Adenomatous Polyps
Certain characteristics of colorectal adenomas at baseline colonoscopy are the basis for decisions about surveillance intervals. Existing data from the National Polyp Study (NPS), a pooled analysis of chemoprevention studies, as well as observational cohort studies support the presence of the following predictors for the development of future advanced adenomas or cancers: (1) three or more adenomas, (2) adenoma size greater than 1 cm, and (3) adenoma with villous features or high-grade dysplasia. A proximal location of adenomas (ascending colon or cecum) may also predict metachronous advanced adenomas, but this has not been well studied to date. In addition, there is a general consensus among many of the studies that individuals with adenomas with lesser findings (eg, one or two subcentimeter adenomas without high-grade dysplasia or villous features) are at lower risk for subsequent advanced adenomas.
By stratifying patients into "lower risk" and "higher risk" groups for future advanced adenoma development based on findings from initial colonoscopy, the NPS has provided evidence-based guidelines for surveillance of postpolypectomy patients. In a randomized comparison of surveillance intervals after colonoscopic removal of newly diagnosed adenomatous polyps, there was no better detection of advanced lesions with surveillance examination 1 year after the initial colonoscopy than with follow-up examination in 3 years. The inference made is that the rate of developing metachronous adenomas with advanced pathology is slow; therefore, the current recommendation for patients with a personal history of three or more adenomas, adenomas of 1 cm or larger, or adenomas with villous or high-grade dysplasia, or any combination of these findings, is surveillance colonoscopy in 3 years. In addition, patients who have more than 10 adenomas removed during one endoscopic examination should be examined in a shorter time interval (<3 years) based on clinical judgment and should be considered for the possibility of an underlying familial syndrome. The standard of care for a sessile, malignant polyp removed by piecemeal fashion is 3–6 months after the initial endoscopic resection.
However, it is important to acknowledge that the timing of surveillance colonoscopy in patients with a history of adenomatous polyps is still evolving. The existing studies assessing subsequent risk for neoplasia after colonoscopic polypectomy have only followed patients for 5–6 years. This is a significant limitation and has led to the current projection that patients without advanced adenomas can wait at least 5 years (and perhaps up to 10 years) for repeat colonoscopy. As a result, further studies are needed to evaluate this "low risk" group in order to confirm the strategy of these intervals.
Winawer SJ, Zauber AG, Ho MN, et al. Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup. N Engl J Med
Individuals with a history of CRC are at risk for recurrent cancer and metachronous neoplasms and require endoscopic surveillance after surgical resection. Anywhere from 2% to 7% of patients with CRC have one or more synchronous cancers in the colon or rectum at the time of initial diagnosis; it is therefore important to perform a complete colonoscopy in the preoperative period. In cases where an obstructing colonic or rectal lesion is detected, CTC or DBCE should be considered perioperatively, and a complete colonoscopy should be performed 3–6 months after surgery. Once the colon is cleared of any synchronous lesions, a postoperative surveillance colonoscopy is recommended at 1 year to evaluate for any metachronous lesions. If the examination at 1 year is normal, the subsequent examination should be at 3 years. If this examination is also found to be normal, surveillance colonoscopy can thereafter be extended to every 5 years. Neither individual randomized controlled clinical trials of intense surveillance with annual colonoscopy nor a meta-analysis of these trials for the purpose of detecting recurrent disease have shown a survival benefit for patients with CRC.
Colonoscopy at 1 year after surgical resection is recommended based on reports of a high incidence of metachronous second cancers noted within the first 2 years after resection. Among an aggregate of studies reporting results from postcancer surveillance colonoscopy, there was an incidence rate of 0.7% metachronous cancers in the first 2 years after resection of the initial primary cancer. This estimate is consistent with data from a tumor registry review in Nebraska, which calculated an annual incidence of 0.35% per year for metachronous cancers. This is considered sufficient information to warrant a colonoscopy at 1 year following surgical resection. However, this should not diminish the importance of a high-quality colonoscopic examination in the perioperative period to exclude synchronous neoplasms.
In addition, it is important to distinguish between rectal and colon cancer because of the differing rates of local recurrence. The recurrence of colon cancer at the anastomotic site occurs in only 2–4% of patients. In contrast, local recurrence rates of rectal cancer when patients have undergone a low anterior resection can be 10 or more times higher. High recurrence rates of rectal cancer are partly a function of surgical technique. Local recurrence rates of cancer can be reduced by using a surgical technique called mesorectal excision, as well as administering radiation and chemotherapy in the neoadjuvant, preoperative setting to patients with locally advanced disease. However, because reported local recurrence rates for rectal cancer across the United States are generally higher than those achieved in case series using total mesorectal excision, there is a rationale for performing periodic examinations of the rectum. Although effectiveness has not been proven, performing proctoscopy at 6-month intervals for the first 2 years after surgical resection can be considered for the detection of a surgically curable recurrence of the original rectal cancer.
When colon or rectal cancer is endoscopically resected and surgery is not needed, follow-up endoscopic examination to inspect the biopsy site within 1 year is a reasonable strategy. As previously noted, colonoscopy is considered the test of choice for the detection of metachronous neoplasms in patients with a history of CRC. CTC has not been evaluated adequately in this setting, and guaiac-based fecal occult blood testing (FOBT) has been considered to have a very low positive predictive value after colonoscopic evaluation.
Rex D, Kahi CJ, Levin B, et al. Guidelines for colonoscopy surveillance after cancer resection: a consensus update by the American Cancer Society and the US Multisociety Task Force on Colorectal Cancer. Gastroenterology
Winawer SJ, Zauber AG, Fletcher RH, et al. Guidelines for colonoscopy surveillance after polypectomy: a consensus update by the US Multisociety Task Force on Colorectal Cancer and the American Cancer Society. Gastroenterology
. 2006;130: 1872–1885.
Family History of CRC or Adenomatous Polyps
An individual's risk of CRC is increased if there is a family history of adenomatous polyps or CRC. The screening recommendations based on familial risk are derived largely from the observed colon cancer risk in relatives of patients with CRC and adenomas diagnosed before age 60 years (Table 22–2). Data from a meta-analysis of 27 studies assessing familial risk of CRC and adenomatous polyps report a relative risk of CRC when a first-degree relative was affected with CRC to be 2.4. The relative risk for CRC if the first-degree relative had an adenomatous polyp was 1.9, with age effects similar to those observed for cancer. In addition, if more than one relative was affected and CRC was diagnosed before age 45 years, the relative risk increased to 4.2 and diminished to 2.2 and 1.8 for ages 45–59 years and older than 59 years, respectively. Therefore, familial risk needs to be readily identified and should prompt the early initiation of screening with colonoscopy.
Table 22–2. Relative Risk of Colorectal Cancer (CRC) Based on Family History.a ||Download (.pdf)
Table 22–2. Relative Risk of Colorectal Cancer (CRC) Based on Family History.a
|One FDR with CRC||2–3|
|One FDR with CRC diagnosed at ≤50 years||3–4|
|Two FDR with CRC||3–4|
|Two SDR with CRC||2–3|
|One FDR with an adenomatous polyp||2|
At present, the U.S. Multisociety Task Force on Colorectal Cancer recommends that for patients who report one first-degree relative under 60 years or two first-degree relatives of any age with adenomatous polyps or CRC, screening colonoscopy should start at age 40 years or 10 years younger than the earliest diagnosis of an affected relative (whichever one comes first) and continue every 5 years (Figure 22–2, Table 22–3). Screening should start at the same time for those patients with a single first-degree relative with CRC or adenomas diagnosed after age 60 years, but surveillance should be performed as for average-risk individuals. The rationale for starting screening at age 40 years is that the incidence of CRC in these patients resembles the risk in persons with no family history but precedes it by approximately 10 years. In addition, a patient reporting a second- or third-degree relative with adenomatous polyps or CRC does not confer additional risk, and therefore, average-risk screening recommendations are sufficient.
Table 22–3. Colorectal Cancer Screening Recommendations. ||Download (.pdf)
Table 22–3. Colorectal Cancer Screening Recommendations.
|Assessed Risk||Age to Initiate||Test||Interval|
FOBT + FS
10 y or
5 y or
Annual FOBT + FS every 5 y
|Personal history of:|
- 1–2 adenomas <1 cm
- ≥3 adenomas <1 cmd
- Adenoma ≥1 cm
- Adenoma with villous features
- Adenomas with HGD complete resection
- Piecemeal resection
- Normal exam with prior adenoma resected
3 y; if normal, every 5 y
3–6 moe; 3 y
- FDR with CRC/adenoma <60 y
- FDR with CRC/adenoma >60 y
- ≥2 FDR with CRC/adenomaf
|Attenuated||10 y earlier than first polyps/CRC diagnosed in family||Colonoscopy||1–2 y|
|Lynch syndromeg||20–25 years||Colonoscopy||1–2 y|
|Crohn or ulcerative colitis|
|Pancolitis||8 y after diagnosis||Colonoscopy||1–2 y|
|Left-sided colitis||15 y after diagnosis||Colonoscopy||1–2 y|
However, it is important to note that no studies to date have reported a reduction in mortality in persons with a family history of CRC or adenomatous polyps who undergo screening. Therefore, the present screening recommendations are considered provisional, and further evidence is needed to better delineate the CRC risk in relatives with adenomatous polyps or CRC as this information continues to evolve.
Johns LE, Houlston, RS. A systematic review and meta-analysis of familial colorectal cancer risk. Am J Gastroenterol
For individuals with a hereditary CRC syndrome, such as familial adenomatous polyposis (FAP) or Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer, or HNPCC), genetic counseling and special screening protocols are recommended (Table 22–4). Readily identifying these individuals is of great importance given the known benefit of intensive endoscopic surveillance and prophylactic surgery on morbidity and mortality. Recognizing these syndromes also has an impact on referral for predictive genetic testing, wherein identifying gene carriers improves the efficiency of cancer surveillance and helps identify family members who require intense management versus those who can receive the standard of care. Additionally, for patients with longstanding inflammatory bowel disease such as Crohn disease or ulcerative colitis, surveillance colonoscopy with systematic biopsies should be performed because the risk of CRC is increased in both conditions.
Table 22–4. Colon Cancer Screening Recommendations for People with Familial or Inherited Risk. ||Download (.pdf)
Table 22–4. Colon Cancer Screening Recommendations for People with Familial or Inherited Risk.
|Familial Risk Category||Screening Recommendation|
|First-degree relative affected with colorectal cancer or an adenomatous polyp at age ≥60 y, or 2 second-degree relatives affected with colorectal cancer||Same as average risk but starting at age 40 y|
|Two or more first-degree relativesa with colon cancer, or a single first-degree relative with colon cancer or adenomatous polyps diagnosed at an age <60 y||Colonoscopy every 5 y, beginning at age 40 y or 10 y younger than the earliest diagnosis in the family, whichever comes first|
|One second-degree or any third-degree relativeb,c with colorectal cancer||Same as average risk|
Engelsgjerd M, Farraye FA, Odze RD. Polypectomy may be adequate treatment for adenoma-like dysplastic lesions in chronic ulcerative colitis. Gastroenterology
Jo WS, Chung DC. Genetics of hereditary colorectal cancer. Semin Oncol
Ullman T, Croog V, Harpaz N, et al. Progression of flat low-grade dysplasia to advanced neoplasia in patients with ulcerative colitis. Gastroenterology
Familial Adenomatous Polyposis
FAP is an autosomal-dominant syndrome that is associated with mutations in the adenomatous polyposis coli (APC) gene. Affected individuals classically develop hundreds to thousands of colorectal adenomas at a young age and have a risk of CRC approaching 100% in the absence of prophylactic colectomy. Annual sigmoidoscopy beginning at age 10–12 years is recommended for persons who have a genetic diagnosis or are at risk of having FAP in order to determine if they are expressing the genetic abnormality. Germline genetic testing should be recommended in persons with an FAP phenotype and should be performed after patients (or parents of children) undergo genetic counseling. If a mutation is identified, other family members can be tested to discern the presence or absence of the same mutation with nearly 100% accuracy. Sigmoidoscopy is performed until affected individuals develop polyps, at which point total colectomy is recommended. Family members who test negative for the gene mutation are considered to be at average risk for CRC.
Although classic FAP can be readily identified, a subset of patients has a less obvious phenotype. Patients with 10 or more cumulative colorectal adenomas but less than 100, are at risk for a variant of FAP called attenuated FAP (AFAP). In these patients, the age of onset of adenomas is approximately 10 years later than with classic FAP. AFAP also has an autosomal-dominant mode of inheritance and, as with classic FAP, is due to mutations in the APC gene. The true incidence and frequency of AFAP is unknown; however, it may account for up to 10% of adenomatous polyposis families and should be considered in individuals with multiple adenomas. Colonoscopy should be used as the initial screening modality in patients suspected of having AFAP, and the age to initiate screening is based on the age of polyp expression or CRC diagnosis in the family. It is reasonable to start colonoscopic screening 10 years earlier than the earliest age of known polyp or CRC diagnosis in the family. As with FAP, germline genetic testing should be considered in persons presenting with the AFAP phenotype.
Lynch syndrome exhibits an autosomal-dominant pattern of inheritance, and affected individuals have a near 80% lifetime risk of developing CRC without intervention. It is predominantly caused by a mutation in one of four of the DNA mismatch repair genes, MSH2, MLH1, MSH6, and PMS2. There are several classification systems for the clinical diagnosis of Lynch syndrome, ranging from the most exclusive Amsterdam Classification to the most inclusive revised Bethesda Guidelines, all relying on personal or family medical histories, or both. Commercial genetic testing is currently available for individuals suspected of having Lynch syndrome, as well as for family members who are at risk for the condition.
Once Lynch syndrome has been diagnosed based on clinical criteria or through genetic testing, an intensive screening program should be instituted. Screening colonoscopy should be recommended every 1–2 years beginning at age 20 and 25 years, or 10 years prior to the youngest CRC case diagnosed within the family (whichever occurs earlier). Annual colonoscopy is recommended after the age of 40 years.
Inflammatory Bowel Disease
The CRC risk is similar in both Crohn colitis and ulcerative colitis, with an estimated lifetime risk of 15–40%. Although direct supporting evidence is lacking, an expert consensus panel has recommended colonoscopic surveillance every 1–2 years for patients after 8 years of pancolitis or after 15 years in those with limited left-sided colitis. If the extent of disease cannot be accurately assessed, patients should undergo surveillance colonoscopy beginning within 8–10 years of disease.
To consider surveillance effective, an extensive biopsy protocol during colonoscopy should be followed. Experts have recommended that biopsy specimens should be taken every 10 cm in all four quadrants and that additional biopsy specimens should be obtained from anastomotic sites (in cases of previous colonic resections), strictures, and mass lesions (other than pseudopolyps). Polyps should be removed by polypectomy, with biopsies of the adjacent flat mucosa to discern if dysplasia is present. In cases where high-grade dysplasia or multifocal dysplasia is found in flat mucosa, patients should be advised to undergo colectomy. However, it is imperative that pathologic confirmation be made by an experienced pathologist in the field of dysplasia in inflammatory bowel disease prior to colectomy. Controversy exists in cases of low-grade dysplasia in flat mucosa and the need for colectomy. If low-grade dysplasia is unifocal or found in areas of inflammation, attempts should first be made to treat the active colitis.
In cases where a mass lesion is detected, it is important to differentiate whether it is a dysplasia-associated lesion or mass (DALM) or if it has arisen from a sporadic adenoma. A DALM is a dysplastic lesion believed to have arisen because of the cancer potential of the colitis and is an indication for colectomy. In contrast, a lesion arising from a sporadic adenoma should be removed in its entirety during colonoscopy and does not require colectomy unless the lesion is not amenable to complete endoscopic resection. Differentiating between DALMs and adenoma-related masses can be difficult and requires extensive review of the endoscopic appearance, histologic findings, presence of dysplasia in the surrounding flat mucosa, patient's age, and duration of disease.
The decision for colectomy should be individualized in cases of long-standing disease based on a number of concomitant factors known to increase CRC risk. These factors include extensive active colitis or ongoing colitis-related symptoms, personal history of primary sclerosing cholangitis, a family history of CRC, age, and life expectancy.
Special Considerations: Hyperplastic & Serrated Polyps
At this time, there is no evidence to suggest that patients with a few small, distally located hyperplastic polyps are at increased risk for CRC. Therefore, such patients should undergo surveillance for CRC similar to that of average-risk individuals.
However, there has been recent literature to suggest that all hyperplastic polyps are not histologically similar and that some variants of hyperplastic polyps may evolve into a unique type of adenoma, called a serrated adenoma. Serrated adenomas resemble hyperplastic polyps with dysplasia and have been linked to the development of sporadic adenocarcinoma with microsatellite instability. Polyps of this type are often large, sessile, and located in the proximal colon. It is important for these neoplastic lesions to be completely removed, and surveillance should follow those recommendations as for typical adenomas.
In addition, there is a recently described syndrome of "hyperplastic polyposis." The following features have been used to define this entity: (1) at least five histologically diagnosed hyperplastic polyps proximal to the sigmoid colon, of which two are greater than 1 cm in diameter, or (2) any number of hyperplastic polyps occurring proximal to the sigmoid colon in an individual who has a first-degree relative with hyperplastic polyposis, or (3) more than 30 hyperplastic polyps of any size distributed throughout the colon. A limited number of studies have suggested an increased risk of CRC in such individuals, although the magnitude of risk has not been determined. A case series of 15 patients fulfilling the preceding criteria did not find any CRC cases within 3 years of follow-up colonoscopic evaluation. Presently, the optimal management for these patients is unclear and requires further study.
Fernández A, Samowitz W, DiSario JA, et al. Phenotypic characteristics and risk of cancer development in hyperplastic polyposis: case series and literature review. Am J Gastroenterol.
Leggett BA, Devereaux B, Biden K, et al. Hyperplastic polyposis: association with colorectal cancer. Am J Surg Pathol.
Terdiman JP, McQuaid KR. Surveillance guidelines should be updated to recognize the importance of serrated polyps. Gastroenterology