Which of the following clients is at the highest risk for colorectal cancer?

Colorectal cancer is a preventable disease. Identification of increased risk and high-risk groups, such as patients with a family history or personal history of CRC, adenomas, genetic syndromes, and those with a personal history of inflammatory bowel disease, is important so that surveillance can be performed at more frequent intervals than in the average-risk individual whose only risk factor is age. Screening in the asymptomatic individual is estimated to cost between $15,000 (US) and $25,000 (US) per year of life saved, which is comparable to breast cancer screening. The most important aspect is education of patients and healthcare practitioners.

Several medical, surgical, and oncology specialty societies periodically update screening recommendations. There are combinations of tests available, such as guaiac-based stool testing, sigmoidoscopy, colonoscopy, and colography. Efficacy in the general population has been demonstrated with a guaiac testing and sigmoidoscopy. Colonoscopy has not been evaluated in a randomized study, but intuitively should be effective in the early detection and prevention of colorectal cancer. Computed tomographic colography or virtual colonoscopy has not been systematically evaluated, and, unfortunately, most of the time is being used in uncontrolled settings, which preclude gathering of meaningful information.

Screening for colorectal cancer remains a problem. Less than 30% of the individuals in whom screening has been recommended have ever been screened. The current American Cancer Society (ACS) colorectal screening recommendations for average risk men and women age 50 years or older include 5 options: (1) an annual fecal occult blood test (FOBT); (2) flexible sigmoidoscopy every 5 years; (3) annual FOBT plus flexible sigmoidoscopy every five years; (4) double contrast barium enema (DCBE) every five years; or (5) colonoscopy every 10 years. The ACS considers the combination of flexible sigmoidoscopy with FOBT a better choice than either FOBT or flexible sigmoidoscopy alone. FOBT of a single stool sample obtained during a digital rectal examination is not an adequate substitute for the recommended at-home collection of two samples from each of three consecutive specimens. A positive FOBT should be followed by a colonoscopy.

It can be strongly argued that the best method for screening is colonoscopy. The latter procedure allows for direct visualization of the colon and, if necessary, polypectomy. Detractors of colonoscopy as a screening tool argue that the cost to society is too high, that there are not enough qualified endoscopists to perform the procedure, that there are risks and discomfort associated with the procedure, and that flexible sigmoidoscopy will allow the identification of patients with significant adenomas to allow the use of colonoscopy in a more efficient way so that patients at a high risk of proximal significant neoplasms can be identified. There is no perfect screening test for CRC. Annual fecal occult blood testing decreases mortality from colorectal cancer between 15% and 33%. A study evaluating a one-time FOBT with sigmoidoscopy revealed that advanced neoplasia, defined as an adenoma 1 cm or larger, a villous adenoma, an adenoma with high-grade dysplasia, or invasive cancer, would have been missed in 24% of the cases. Two large studies evaluating the risk of advanced proximal neoplasia in patients undergoing evaluation of the distal colon followed by colonoscopy revealed that advanced proximal neoplasia would not have been detected in 50% and 62% of patients because there were no distal neoplasms that would have warranted full colonoscopy. In the National Polyp Study, double-contrast barium enema failed to detect 48% of adenomas greater than 1 cm. Colonoscopy is not perfect. Visualization of the cecum is not always possible. In addition, there is morbidity associated with colonoscopy. The risk of perforation is small after diagnostic colonoscopy, but is higher after polypectomy. Problems with conscious sedation and bleeding after polypectomy have been reported. Encouraging single-institution results have been published with colography. However, patients still have to undergo bowel preparation, the expertise is variable, and there is no standardized software. Patient acceptance for this procedure may be higher and therefore in the future this may be a useful screening procedure. Screening for colorectal cancer appears to be cost-effective when compared to no screening. Each modality discussed above has its advantages and disadvantages. Therefore, screening for colorectal cancer has to be individualized according to the resources available and the patient as well as healthcare provider preferences.

An area being evaluated as a potential screening tool is the detection of molecular markers in the stool of patients. Ahlquist and colleagues reported on the feasibility of a multitarget DNA-based stool assay. The specific assay targeted K-ras, APC, p53, Bat 26, and long or high-molecular-weight DNA. In 61 stool samples analyzed, the sensitivity was 91% for cancer and 82% for large adenomas. The specificity was 93%.

Risk factors for Colorectal Cancer

Age

The incidence of colorectal cancer increases after age 50 years. In the Surveillance, Epidemiology and End Results statistics for the period 1995 to 1999, the incidence rate of colorectal cancer was 48 per 100,000 population for individuals between 40 and 49 years of age, while it was 327 per 100,000 population for individuals aged 60 to 69 years. The incidence rate increased with each subsequent decade age.

Prior History of Adenomas

A personal history of adenomas will increase the risk of subsequent adenomas and thus of colorectal cancer. However, not all adenomas will become malignant and several investigators have attempted to outline particular characteristics of polyps that will increase the risk of recurrent adenomas after polypectomy. Among these characteristics are histology, size, and number of adenomas.

If the adenoma carcinoma sequence can be interrupted, then colorectal cancer incidence should decrease. This was noted in the National Polyp Study. Patients who underwent complete colonoscopy and removal of one or more colorectal adenomas were prospectively evaluated with colonoscopy at intervals of 1 and 3 years. After adjusting for age, gender, and polyp size, at mean follow-up of 5.9 years, patients who underwent periodic colonoscopy had a lower-than-expected rate of colorectal cancer (76% to 90%) when compared to three reference groups; two groups in which the colon polyps were not removed and a general population registry.

In the National Polyp Study, there were no differences in the detection of adenomas with advanced features in patients randomized to a 1-year or a 3-year followup after polypectomy. However, this interval should be individualized according to the characteristics, size, and number of polyps detected at index colonoscopy. The current ACS recommendations for follow-up after polypectomy depend on the size of the adenomas (less than or greater than 1 cm), the number of adenomas, degree of dysplasia or villous changes. In patients with an adenoma less than 1cm in size, colonoscopic follow-up is recommended 3 to 6 years post polypectomy. If the colonoscopy is normal then follow-up as per average-risk patient. If there are multiple adenomas, or high grade dysplasia or villous histology, colonoscopy is recommended within three years of polypectomy.

Family History of CRC and Adenomas

Family history of colorectal cancer in a first-degree relative increases the risk of colorectal cancer two- to threefold. The earlier the diagnosis of CRC, the higher risk. It has been reported that the colon cancer risk of an individual with a first-degree relative is about the same at age 40 years as for the general population at age 50 years. In addition, the more relatives affected, the higher the risk. Second-degree relatives with colorectal cancer also increase an individual's risk of CRC, but by about 25% to 50% above the average risk.

Family history of adenomas also increases the relative risk of colorectal cancer. In first-degree relative with adenomas, the relative risk of colorectal cancer was 1.78. The younger the affected individual, the higher the risk of CRC for the siblings. This was noted in the National Polyp Study, especially if the adenoma was diagnosed at age 60 years or younger.

Colonoscopy is recommended beginning at either age 40 years or 10 years before the youngest CRC in the immediate family for individuals with a first-degree relative with either colorectal cancer or adenomas diagnosed at age 60 years or younger, or for any individuals with two first-degree relatives whose family does not have one of the inherited colorectal cancer syndromes. Colonoscopy should be repeated every 5 years.

Prior History of Colorectal Cancer

After curative resection, patients with colorectal cancer are at risk of recurrent disease. However, the main purpose of endoscopic surveillance is to detect metachronous lesions. The incidence of metachronous colorectal cancer and adenomas in patients with a personal history of CRC is approximately 6% and 25%, respectively. Rarely, isolated anastomotic recurrences are diagnosed. Colonoscopy is recommended within 1 year of cancer resection and if normal, a repeat exam in 3 years. If the latter exam is normal, then the interval could be increased to every 5 years.

Familial Adenomatous Polyposis

Hundreds to thousands of polyps throughout the large bowel characterize classic FAP. It is an autosomal dominant inherited syndrome with a penetrance approaching 100%. If the colorectal adenomas are left untreated, patients with FAP invariably will develop colorectal cancer. The median age of adenoma diagnosis is 15 years. In untreated patients, the mean age of colorectal cancer diagnosis and colorectal cancer death is 39 years and 42 years, respectively. In the milder phenotypic variant, attenuated adenomatous polyposis coli (AAPC), colorectal polyps are less numerous and colorectal carcinoma, in general, will occur in the early fifties.

Surveillance in FAP should start at age 10 to 12 years. Annual flexible sigmoidoscopy is recommended for all first-degree relatives of affected individuals. Unless adenomas are noted, in which case colonoscopy is the procedure of choice, annual flexible sigmoidoscopy should continue until age 18 to 20 years, at which time colonoscopy should be performed every year. If at age 30 years there have been no adenomas, the interval between colonoscopies can be lengthened to between 2 and 3 years. Because APC mutations can be detected in the germ line of the affected patients, genetic testing is recommended for affected individuals. If a mutation is known in the family, then individuals at risk can be tested for that mutation and those in whom no mutation is detected can be spared intensive surveillance and fall into the general population risk. It must be noted that genetic testing should be undertaken in an environment in which there is genetic counseling and psychological support. Needless to say, informed consent is required.

Hereditary Nonpolyposis Colorectal Cancer

HNPCC is an autosomal dominant syndrome characterized by early age onset of colorectal cancer, right-sided predominance, excess synchronous and metachronous colorectal neoplasms, and extracolonic malignancies such as endometrial cancer, small-bowel cancer, renal, pelvis, and ureter cancers, and skin lesions such as sebaceous adenomas, keratoacanthomas, and sebaceous carcinoma. The median age of onset of CRC is 45 years. Endometrial cancer can be the index carcinoma in 35% of female patients.

Adenomas do occur in HNPCC. Currently, it is believed that once adenomas occur in HNPCC, they progress to carcinoma faster than in sporadic CRC patients. Colonoscopy should be started at age 20 years. Surveillance with colonoscopy at least every 3 years decreased colorectal cancer rate by 62% and decreased mortality from colorectal cancer by 65%. Others advocate colonoscopy starting at age 21 years at an interval of every 1 to 2 years until age 40 years, and then annually thereafter. Similar principles apply for genetic testing in HNPCC as FAP except that children are not tested because the onset of cancer is generally at an older age than the onset of adenomas in FAP.

Hamartomatous Polyposis Syndromes

Peutz-Jeghers and juvenile polyposis are the most common hamartomatous polyposis syndromes predisposing to colorectal cancer. Peutz-Jeghers patients are also at risk of stomach, pancreas, breast, and uterine carcinoma, as well as ovarian sex cord tumors, Sertoli cell tumors, and adenoma malignum of the cervix. In addition to colorectal cancer, juvenile polyposis patients are at risk of gastric, duodenal, and pancreatic cancers. In both of these syndromes, there are no evidence-based surveillance recommendations. The recommendations have to be individualized. Genetic testing is also available for affected patients.

Crohn Disease

The incidence and characteristics of colorectal cancer in Crohn disease have been reported to be similar to ulcerative colitis. There are no specific recommendations for surveillance in Crohn disease. However, following the model of ulcerative colitis, recommendations can be made for colonoscopy after 8 years of diagnosis and then every 1 to 2 years. Consideration should be given to random biopsies every 10 cm.

Ulcerative Colitis

In a meta-analysis of 116 publications in the English language, Eaden and colleagues noted that the prevalence of CRC in ulcerative colitis (UC) patients was 3.7%, increasing to 5.4% for those individuals with pancolitis. These authors estimated that the cumulative risk of CRC for any patient with UC was 2% at 10 years, 8% at 20 years, and 18% at 30 years.

Surveillance in UC depends on the extent of the disease and the duration. It is recommended that annual colonoscopy should be performed after 8 years of pancolitis. If the disease is confined to the left side of the colon, then surveillance can be started at a later time. It is imperative to perform random biopsies every 10 cm. If there is severe dysplasia in the specimens, consideration should be given to surgery, as there is a high incidence of occult cancer in the colon.

What client is at the highest risk for colorectal cancer?

Which of the following is a risk factor for colorectal cancer?

Which group is at highest risk for cancer?

Which region is most likely to be at risk for colorectal cancer?