Table 7. Recommended Screening Intervals by Spigelman Stage continued...
Studies have reported whole exon deletions in 12% of FAP patients with previously negative APC testing.[124,125] For this reason, deletion testing has been added as an optional adjunct to sequencing of APC. Furthermore, mutation detection assays that use MLPA are being developed and appear to be accurate for detecting intragenic deletions.MYH gene testing may be considered in APC mutation–negative affected individuals. (Refer to the Colon Cancer Genes section of this summary for more information.)
Patients who develop fewer than 100 colorectal adenomatous polyps are a diagnostic challenge. The differential diagnosis should include AFAP and MYH-associated colorectal neoplasia (also reported as MYH-associated polyposis or MAP). AFAP can be diagnosed by testing for germline APC gene mutations. (Refer to the Attenuated Familial Adenomatous Polyposis (AFAP) section in the Major Genetic Syndromes section of this summary for more information.) MYH-associated neoplasia is caused by germline homozygous recessive mutations in the MYH gene.
Presymptomatic genetic testing removes the necessity of annual screening of those at-risk individuals who do not have the gene mutation. For at-risk individuals who have been found to be definitively mutation-negative by genetic testing, there is no clear consensus on the need for or frequency of colon screening, though all experts agree that at least one flexible sigmoidoscopy or colonoscopy examination should be performed in early adulthood (by age 18–25 years).[20,21] Colon adenomas will develop in nearly 100% of persons who are APC gene mutation positive; risk-reducing surgery comprises the standard of care to prevent colon cancer after polyps have appeared.
Individuals at risk of FAP, because of a known APC mutation in either the family or themselves, are evaluated for onset of polyposis by flexible sigmoidoscopy or colonoscopy. Once an FAP family member is found to manifest polyps, the only effective management to prevent CRC is eventual colectomy. In patients with classic FAP identified very early in their course, the surgeon, endoscopist, and family may choose to delay surgery for several years in the interest of achieving social milestones. In addition, in carefully selected patients with AFAP (those with minimal polyp burden and advanced age), deferring a decision about colectomy may be reasonable with surgery performed only in the face of advancing polyp burden or dysplasia.
The recommended age at which surveillance for polyposis should begin involves a trade-off. On the one hand, someone who waits until the late teens to begin surveillance faces a remote possibility that a cancer will have developed at an earlier age. Although it is rare, CRC can develop in a teenager who carries an APC mutation. On the other hand, it is preferable to allow people at risk to develop emotionally before they are faced with a major surgical decision regarding the timing of colectomy. Therefore, surveillance is usually begun in the early teenage years (age 10–15 years). Surveillance has consisted of either flexible sigmoidoscopy or colonoscopy every year.[84,130,131] If flexible sigmoidoscopy is utilized and polyps are found, colonoscopy should be performed. Historically, sigmoidoscopy may have been a reasonable approach at the time in identifying early adenomas in a majority of the patients. However, colonoscopy must be considered the tool of choice in light of (a) improved instrumentation for full colonoscopy, (b) safer and deeper sedation (Propofol), (c) recognition of AFAP, in which the disease is typically most manifest in the right colon, and (d) the growing tendency to defer surgery for a number of years. Individuals who have tested negative for an otherwise known family mutation do not need FAP-oriented surveillance at all. They are recommended to undergo average-risk population screening. In the case of families in which no family mutation has been identified in an affected person, then clinical surveillance is warranted. Colon surveillance should not be stopped in persons who are known to carry an APC mutation but who do not yet manifest polyps, since adenomas occasionally are not manifest until the fourth and fifth decades of life. (Refer to the Attenuated Familial Adenomatous Polyposis (AFAP) section of this summary for more information.) (Refer to the PDQ summary on Colorectal Cancer Screening for more information on these methods.)
In some circumstances, full colonoscopy may be preferred over the more limited sigmoidoscopy. Among pediatric gastroenterologists, tolerability of endoscopic procedures in general has been regarded as improved with the use of deeper intravenous sedation.[84,132]
Table 8 summarizes the clinical practice guidelines from different professional societies regarding diagnosis and surveillance of FAP.