Familial Adenomatous Polyposis

Background

• Familial adenomatous polyposis (FAP) is a rare condition characterized by:
  • the presence of many, and sometimes hundreds of, colorectal adenomatous polyps on endoscopy
  • a lifetime risk of colorectal cancer (CRC) approaching 100% without surgical treatment
  • an increased risk of extracolonic lesions and tumors
• FAP is caused by a pathogenic variation in the tumor suppressor adenomatous polyposis coli (APC) gene and is inherited in an autosomal dominant manner.
• Attenuated AFAP is a type of FAP characterized by:
  • the presence of between 10 and 100 colorectal adenomatous polyps on endoscopy (with > 100 lifetime polyps generally considered the transition point from AFAP to FAP)
  • a lifetime risk of CRC of about 70%
  • increased risk of extracolonic lesions and tumors, although less risk than in classic forms of FAP

Evaluation

• Patients commonly present with a family history of FAP, although about 30% of patients present with a de novo mutation.
• Additional initial indicators of FAP may be ≥ 10 colorectal adenomatous polyps on endoscopy; gastrointestinal (GI) symptoms such as rectal bleeding, chronic diarrhea, change in bowel movement pattern, and abdominal pain; and extracolonic manifestations including congenital hypertrophy of the retinal pigment epithelium (CHRPE).
• Suspect FAP when > 100 adenomatous polyps are present along the entire colon at a young age.
• Suspect AFAP when < 100 adenomatous polyps are present at an older age (35-40 years or older).
• Order genetic testing to confirm the diagnosis of FAP or AFAP, including a polyposis and CRC multigene panel to rule out differential diagnoses, for patients with:
  • a history of ≥ 20 colorectal adenomatous polyps during their lifetime (Strong recommendation)
  • a history of ≥ 10 colorectal adenomatous polyps found on a single endoscopy (Strong recommendation)
  • a family history of an APC gene pathogenic variation in a first-degree relative (Strong recommendation)
• Consider genetic testing for patients with:
  • multifocal or bilateral/unilateral CHRPE lesions (Weak recommendation)
  • a desmoid tumor, hepatoblastoma, or a cribriform-morular variant of papillary thyroid cancer or who meet the criteria for serrated polyposis syndrome (Weak recommendation)

Management

• Due to the high risk of CRC, aggressive colorectal surveillance and eventual colorectal surgery are crucial for all patients with FAP.
• Start colorectal screening in patients with FAP with colonoscopy or flexible sigmoidoscopy beginning at a young age (10-14 years), and continue surveillance every 1-3 years (Strong recommendation).
• Consider screening in patients with AFAP with colonoscopy or flexible sigmoidoscopy every 1-2 years starting at age 18-20 years (Weak recommendation).
• For family members of patients with FAP, including family members in whom an APC gene pathogenic variant has not been identified or at-risk family members on whom genetic testing has not yet been done, start colorectal screening with colonoscopy or flexible sigmoidoscopy at a young age (10-15 years), with surveillance every 1-2 years until either a clinical diagnosis is made or patients reach the age for screening guidelines in average-risk adults (Strong recommendation).
• For family members of patients with AFAP, including family members in whom an APC gene pathogenic variant has not been identified or at-risk family members on whom genetic testing has not yet been done, consider colorectal screening with colonoscopy every 2 years beginning at age 18-20 years (Weak recommendation).
• For asymptomatic patients at familial risk for FAP or AFAP and who test negative for an APC gene pathogenic variant, consider colorectal screening as recommended for the general population (Weak recommendation).
• Consider polypectomy every 1-2 years in patients with a history of AFAP in which a small adenoma burden can be handled with colonoscopy (Weak recommendation).
• Consider colectomy with ileorectal anastomosis (IRA) in patients with a history of AFAP in which an adenoma burden cannot be handled with colonoscopy (Weak recommendation).
• Consider risk-reducing colorectal surgery, which may consist of
  • colectomy with IRA for less severe disease progression and AFAP
  • proctocolectomy with ileal pouch-anal anastomosis for severe polyposis
  • proctocolectomy with end ileostomy for advanced rectal cancer
• Perform regular surveillance of retained lower GI tract following colectomy in patients with FAP (Strong recommendation).
• For surveillance of extracolonic manifestations in patients with FAP, such as:
  • duodenal/periampullary cancer: start upper GI endoscopy around age 20-25 years (Strong recommendation)
  • hepatoblastoma in children: consider abdominal ultrasound and alpha-fetoprotein serum levels every 3-6 months from birth until age 5-7 years (Weak recommendation)
  • thyroid cancer: consider ultrasounds and/or regular exams starting in the teens or twenties in patients with FAP and/or AFAP (Weak recommendation)
  • desmoid tumors: consider abdominal imaging if patients have any suggestive symptoms or personal history (Weak recommendation)
• Consider chemopreventative medication for control of rectal polyposis in the retained rectum of select patients with FAP and progressive polyp burden (Weak recommendation).