CRC Surveillance Behaviors of Typical and Attenuated FAP Families
Objectives: Although enhanced colorectal surveillance is recommended for members of familial adenomatous polyposis (FAP) families, little is known about individual-level adherence behavior. This study examined factors associated with recent use of colorectal cancer (CRC) surveillance among FAP patients and their at-risk relatives.
Methods: This cross-sectional study conducted a computer-assisted telephone survey among 150 members of 71 extended families with classic (FAP) or attenuated adenomatous polyposis (AFAP). Participants were enrolled in a university-based hereditary CRC registry or were first-degree relatives of enrollees. Both qualitative and quantitative data were collected and analyzed.
Results: Surveillance behavior varied by disease status. Fifty-four percent of 71 participants with a personal history of FAP and 42% of 79 at-risk relatives reported recent use of CRC surveillance recommendations. In multiple logistic regression analysis, lack of patient recall of provider recommendation for an endoscopic examination of the colon (OR 4.8, 95% CI 1.8–13.1), lack of health insurance or no reimbursement for CRC surveillance (OR 3.6, 95% CI 1.2–10.5), and/or the belief that their relative risk of CRC is not increased (OR 3.1, 95% CI 1.2–7.1) were independently associated with not having had a recent colonoscopy or sigmoidoscopy.
Conclusions: Despite the known benefits of CRC surveillance, a substantial proportion of FAP family members did not have a recent colonoscopy or endoscopy. Interventions targeted at both clinicians and patients are needed to improve surveillance behavior. These data are also important in designing decision support tools to assist clinicians in identifying and managing high-risk patients.

As many as one-third of colorectal cancers (CRC) can be attributed to inherited predisposition. Familial adenomatous polyposis (FAP) is inherited by autosomal dominant transmission and is the second most common genetic CRC syndrome, accounting for less than 1% of all incident CRC. The condition includes Gardner syndrome, approximately two-thirds of families with Turcot syndrome, and attenuated familial adenomatous polyposis (AFAP) coli. Classic FAP and its variants, including AFAP, arise from mutations in the APC gene and in genes that have not yet been identified. Genetic testing can only yield a true negative result for FAP when a genetic mutation has already been identified for a particular family. Individuals with FAP show numerous colonic adenomatous polyps and generally develop CRC at an earlier age than persons in the general population.

It is recommended that patients with classic and attenuated FAP be managed by physicians or centers with expertise in FAP and that care be individualized based on genotype, phenotype, and personal factors. Patients suspected of having classic or attenuated FAP or who have a family history of the disease should be referred to a genetic counselor for counseling and APC mutation testing. Clinical genetic counseling and testing allows for focused screening and medical management in individuals who are deemed at greater risk because of the presence of a deleterious mutation. Clinical genetic testing of the APC gene is available and is considered standard care for FAP/AFAP patients because of the high penetrance and the documented value of prophylactic colectomy. If a mutation is identified, relatives then become genetic testing candidates. APC mutation-positive carriers should have intensive screening and individuals who test negative for a known family mutation do not need intensive screening. Individuals who are at 50% risk of inheriting a deleterious APC mutation and whose genetic status is unknown should be screened according to the guidelines for mutation carriers.

Classic FAP is characterized by the formation of hundreds to thousands of colonic polyps, some of which, if not removed, eventually lead to cancer. The average age of onset of polyps is 16 yr and the mean age at CRC diagnosis in individuals with an intact colon is 39 yr. A clinical diagnosis is made when over 100 colonic adenomatous polyps are observed or when a person at 50% risk of developing the disease is found to have multiple adenomas. The lifetime risk of CRC in affected individuals is virtually 100% if the colon and rectum are not removed. Polyps are distributed throughout the colon with a slight distal colonic prevalence. Current guidelines recommend that individuals with a clinical diagnosis of FAP should undergo annual colonoscopy and polypectomy or polyp ablation if the polyp burden is low. Individuals who have a documented APC mutation but polyposis is not yet evident should undergo annual sigmoidoscopy beginning at age 10–15 yr. For individuals who are at risk for FAP and their mutation status is unknown (the family mutation has been found but they have not undergone APC mutation testing) or the family mutation has not been found, CRC surveillance recommendations include flexible sigmoidoscopy or colonoscopy beginning at age 10–12 yr: every 12 months until age 24, every 2 yr until age 34, every 3 yr until age 44 yr, and then every 3–5 yr thereafter. Because of the chance that asymptomatic individuals may have an attenuated form of FAP, substituting colonoscopy every 5 yr should be considered beginning at age 20 yr. Proctocolectomy or colectomy is recommended if polyposis is dense or if there are dysplastic polyps.

It is estimated that 2–15% of families with adenomatous polyposis have the attenuated variant of FAP, termed AFAP. Compared to classic FAP, the typical manifestations of AFAP are fewer colonic adenomas (typically less than 100, range 0 to >1,000), a high variability of polyp number, a later age of onset of colorectal adenomatous polyposis (15 yr later than patients with classic FAP), later age of onset of CRC (mean 43–58 yr, range 12–81 yr), and a more limited expression of the extracolonic features. To facilitate appropriate treatment and follow-up, individuals who present with ≥10-20 adenomatous polyps, have a family history of AFAP, or report family members with multiple polyps should be evaluated for AFAP and referred to a genetic counselor and physician specialist for further evaluation. In contrast to classic FAP, the lifetime penetrance of CRC in persons with AFAP is less than 80%, and rectal cancer is rarely observed. Because AFAP patients have a tendency to develop adenomas in the proximal colon, colonoscopy is preferred to sigmoidoscopy as a screening approach. Current cancer surveillance recommendations include colonoscopy every 1-2 yr among those with a personal history of AFAP and every 2-3 yr beginning in the late teens for high-risk individuals (APC mutation positive, family APC mutation not found, or at-risk patient not tested for APC mutation). Colectomy should be considered when the number of polyps exceeds 20 (somewhat arbitrary), some polyps are greater than 1 cm, or advanced histology is evident. It is also recommended that early colectomy be considered in patients with a personal history of AFAP if there is a family history of CRC under age 40 yr or the patient is not compliant with surveillance. About one-third of patients with AFAP will not need colectomy, but can be safely managed with interval colonoscopy and polypectomy.

As with classic FAP, the risk of duodenal cancer (3-5% lifetime risk) and stomach cancer (0.5-1%) is increased. Therefore, screening for these cancers is recommended in patients with both classic and attenuated FAP with both end and side-viewing upper gastrointestinal endoscopy beginning at age 25-30 yr every 6 months to 4 yr depending on the polyp burden and the presence of advanced histology (e.g., severe dysplasia). Pancreaticoduodenectomy is recommended for severe duodenal polyposis not manageable by polypectomy or for severe dysplasia.

Surveillance behaviors among members of FAP and AFAP families are not known. However, numerous studies indicated that recent and regular use of CRC surveillance tests in relatives of CRC patients who are at moderate to high risk for the disease is suboptimal. Health behavior theories and studies of CRC screening suggest that sociodemographic factors, knowledge of one's genetic status, risk perceptions, psychological status, and social support could motivate surveillance behavior. Thus it is of interest to identify factors associated with surveillance behaviors among persons who have or are at risk for typical and attenuated adenomatous polyposis. The study reported here is a cross-sectional survey that determined the proportion of high-risk individuals from FAP and AFAP families who reported recent use of colonoscopy or sigmoidoscopy. We were particularly interested in identifying factors that were associated with nonuse of recommended surveillance tests to identify targets for interventions to enhance surveillance behavior.