Approach

The management of familial adenomatous polyposis (FAP) is guided by colonoscopic surveillance and the presence of adenomas.

Prophylactic proctocolectomy is the main means for preventing colorectal cancer in FAP.

Surveillance colonoscopy

Patients with a family history of FAP/attenuated FAP (AFAP) who are adenomatous polyposis coli (APC)-positive should undergo surveillance colonoscopy to identify and/or monitor colonic adenomas.[9][24][30]​​[38]​​[41]

For patients with FAP, the National Comprehensive Cancer Network (NCCN) advises that colonoscopy should be offered starting from ages 10 to 15 years. Other guidance, including from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition, recommend that this surveillance can begin slightly later, from age 12 years onward.[24][30][38]​​ For patients with AFAP, colonoscopic surveillance should begin in the late teens, and generally no later than 20 years age.[9][38]

Frequency of colonic surveillance is individualized depending on colonic phenotype and is typically undertaken between every 1 and 3 years.[9][24]​​​[38]​ The presence of alarm symptoms such as anemia, rectal bleeding, increased bowel movements, and mucous discharge should prompt urgent colonoscopy for any patient, regardless of age or colonic phenotype.[24][38]

There is no single consensus for the absolute or relative indications for surgery. In patients with FAP, surgery is generally recommended following detection of colonic adenomas, but timing must be individualized and depends on the distribution, size, and histology of colorectal polyps.[24][28]​ In cases of AFAP, surgery is largely guided by adenoma burden than adenoma presence.[9] 

The American College of Gastroenterologists advise absolute indications for immediate colorectal surgery in patients with FAP, or attenuated FAP, include:[29]​​

  • Documented or suspected colorectal cancer

  • Significant symptoms related to colonic neoplasia (e.g., gastrointestinal bleeding)

These indications are also supported by the British Association of Gastroenterology and the Association of Coloproctology of Great Britain and Ireland.[30]

Relative indications for surgery include:​[29]

  • Presence of multiple adenomas >6 mm

  • Significant increase in adenoma number

  • Presence of adenoma with high-grade dysplasia

  • Inability to adequately survey the colon due to multiple diminutive polyps

The European Hereditary Tumor Group (EHTG) and European Society of Coloproctology (ESCP) recommend, for patients with FAP, indications for immediate colorectal surgery include:[38]

  • Certain or suspected cancer

  • Severe symptoms from polyposis

  • Severe disease (>1000 polyps identified at colonoscopy)

  • Unfavorable histologic features (e.g., villous adenoma)

Indications for planned surgery include:[38]

  • Polyp >10 mm in diameter

  • Favorable histology features

  • Substantial increase in polyp number between examinations

  • Sparse disease (100-1000 polyps)

Surgery for FAP

Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the preferred surgery for most patients with FAP because it prevents rectal cancers.[9]​ However, some patients may require (or choose) total abdominal colectomy with ileorectal anastomosis (IRA), or total proctocolectomy with permanent end ileostomy.

Total proctocolectomy with ileal pouch-anal anastomosis (IPAA)

This procedure is offered to patients with classical FAP, patients with attenuated FAP with numerous polyps resulting in carpeting of the rectum, those with curable rectal cancer complicating the polyposis, and those who have previously undergone IRA and now have an unstable rectum in terms of polyp number, size, or histology. The procedure is usually not offered to patients with incurable cancer, those with an intra-abdominal desmoid that may interfere with the completion of surgery, those with anatomic, physiologic, or pathologic contraindications to an IPAA, or where there is concern regarding the ability of patients to participate in close endoscopic surveillance following surgery.[9]

The advantages of total proctocolectomy with IPAA are that the risk of developing rectal cancer is negligible and a permanent stoma is not needed. The disadvantages are that it is a complex operation, a temporary stoma is usually needed, and there is a small risk of bladder or sexual dysfunction, and anal sphincter injury. Bowel function, although usually reasonable, is also somewhat unpredictable. The ileal pouch requires surveillance, and the area of the IPAA should still be examined due to the fact that residual anal transitional zone mucosa may remain.[9] Mucosectomy to maximize removal of rectal mucosa may be considered in IPAA.[42]

Hand-sewn or stapled IPAA techniques may be used. Hand-sewn IPAA involves the removal of all colorectal mucosa, and is therefore associated with decreased risk for polyps occurring post-operatively in the anal transitional zone, compared with stapled anastomosis. It may be the preferred technique for IPAA for selected patients with FAP.[43] This would include patients with polyps in the transitional zone that may be difficult to clear without mucosectomy. Retrospective data from a large, prospective, institutional genetic registry of patients with FAP showed that although stapled IPAA has a higher incidence of anal transitional zone polyps requiring treatment, compared with hand-sewn IPAA, the incidence of anal transitional zone adenocarcinoma was similar between the two groups.[44] The stapled anastomosis is associated with better long-term bowel function than a hand-sewn anastomosis. It is therefore the preferred technique for the surgical management of patients with FAP in some centers.[44]

There is evidence that laparoscopic IPAA is a feasible and safe procedure, although large, good-quality trials examining differences between laparoscopic and open approaches in terms of postoperative complications, cosmesis, quality of life, and costs are needed.[45][46][Figure caption and citation for the preceding image starts]: Brooke ileostomy in familial adenomatous polyposis: adenoma riskFrom the personal collection of Lisa A. Boardman, MD; used with permission [Citation ends].com.bmj.content.model.Caption@78da66fc

Female patients should be counseled that the IPAA is associated with an increase in infertility.[47] For patients who have undergone IPPA, an annual pouchoscopy is necessary for pouch polyp surveillance.[48]

Total abdominal colectomy with IRA

This is an option for patients with FAP with few or no rectal adenomas.[12][28]​​ Because nearly one quarter of patients with FAP treated with IRA develop rectal cancer in the retained rectal mucosa without follow up, patients who have undergone this procedure require annual proctoscopy.[9]​ In one study, 13% of patients with FAP treated with IRA developed rectal cancer a median of 10 years after surgery.[49] The risk of cancer development in the rectal stump rises considerably after age 50 years. If the rectum becomes unstable, a proctectomy with either an IPAA or end ileostomy is recommended.[9]​ The benefits of IPAA versus IRA should be thoroughly discussed with the patient.[47][50][51]

Patients who have IRA have better continence and bowel function following surgery, compared with patients having IPAA.[52]

Women of childbearing age may choose IRA until after childbearing, when they can convert to IPAA.

IRA conversion to IPAA

In some instances, IRA can be converted to IPAA. This was the case in 8% of patients in a retrospective review of patients with FAP. Aside from an increased risk of wound infection in 9% of those converted to IPAA compared with <1% with IPAA as the first operation, no other significant complications were associated with IPAA following an IRA.[53]

Proctocolectomy with end ileostomy

This is rarely indicated as a prophylactic procedure because alternative approaches are available that do not involve a permanent stoma. A proctocolectomy with end ileostomy removes all risk for rectal cancer, but is associated with a risk of bladder or sexual dysfunction. It may be offered to patients with a low, locally advanced rectal cancer, patients who cannot have an ileal pouch due to a desmoid tumor, patients with a poorly functioning ileal pouch, patients who have a contraindication to an IPAA (e.g., concomitant Crohn disease, poor sphincter function), and patients in whom there is a concern for participation in close endoscopic surveillance after surgery. Proctocolectomy with continent ileostomy is offered to patients who are motivated to avoid end ileostomy because they are either not suitable for proctocolectomy with IPAA (e.g., patients who have had previous pelvic surgery or who have shortening of the mesentery) or they have a poorly functioning IPAA. This is a complex operation with a significant risk for reoperation.[9]

Management of desmoid tumors

Intra-abdominal desmoid tumors are one of the leading causes of death in patients with FAP.[54]

Desmoid tumors have unpredictable behavior with poorly understood biology, resulting in a lack of standardized medical and surgical therapies. Management of desmoids is difficult and they often recur in spite of treatment. Patients with FAP and desmoid tumors should be referred to centers specializing in management of desmoid tumors.

Pharmacologic therapy is usually the preferred initial approach.[28]​ Surgery can stimulate intra-abdominal desmoid tumor growth in patients with FAP and is only typically offered to symptomatic patients who do not respond to initial medical therapy.[28] 

Intra-abdominal desmoid staging systems have been developed to help predict associated mortality. Five-year survival of patients with stage I, II, III, and IV intra-abdominal desmoid tumors was 95%, 100%, 89%, and 76%, respectively (P <0.001). Severe pain, opioid dependence, tumor size larger than 10 cm, and need for total parenteral nutrition were shown to further define survival within stages. The 5-year survival rate of a stage IV patient with all of the above-mentioned risk factors was only 53%.[55]

Available treatments include cyclo-oxygenase (COX)-2 inhibitors (e.g., celecoxib) or combined COX-1 and COX-2 inhibitors (e.g., sulindac), antiestrogens (e.g., tamoxifen), chemotherapy and radiation therapy, and surgery. Imatinib has been associated with both partial response and growth stabilization, even in desmoids that do not have apparent mutations in the KIT tyrosine kinase oncogene.[56]​ There are no controlled trials comparing these various modalities of treatment. Complicating our understanding of the impact of these treatments is the phenomenon of spontaneous regression of desmoids, which may occur in up to 10% of cases.[57][58]

Management of duodenal polyps

In more than 90% of patients with FAP, duodenal adenomatous polyposis develops. Upper gastrointestinal tract surveillance with endoscopy is an important aspect of management, as duodenal cancer may develop in up to 10% of patients.[9]

The Spigelman criteria are used to assess the severity of polyps:[37]

  • Duodenal/periampullary polyp number (1-4 = 1 point; 5-20 = 2 points; >20 = 3 points)

  • Size (1-4 mm = 1 point; 5-10 mm = 2 points; >10 mm = 3 points)

  • Histology (tubular = 1 point; tubulovillous = 2 points; villous = 3 points)

  • Degree of dysplasia (low grade = 1 point; high grade = 3 points).

A score of 0 points is classified as stage 0 disease, 1 to 4 points is classified as stage 1 disease, 5 to 6 points is classified as stage 2 disease, 7 to 8 points is classified as stage 3 disease, and 9 to 12 points is classified as stage 4 disease.

At-risk patients found to have colorectal adenomas, as well as known APC gene carriers, should have forward- and side-viewing esophagogastroduodenoscopies at least every 5 years.

The American Society of Colon and Rectal Surgeons and the National Comprehensive Cancer Network recommend that screening for duodenal adenomas begin at ages 20-25 years, although this may be offered to younger patients if there is a family history of duodenal cancer or significant duodenal polyp burden.[9][28][30]​​​​​​​​ The American College of Gastroenterologists and the European Society of Medical Oncology advise a later starting age of 25-30 years.[29][30][40]​​​​​​​ Endoscopy should be repeated every 4-5 years until polyps are found.[29][40]

Once polyps develop, the Spigelman criteria can be used to determine the appropriate surveillance intervals:[37]

  • Stage 0: 3-5 years

  • Stage 1: 2-3 years

  • Stage 2: 1-2 years

  • Stage 3: 6-12 months

  • Stage 4: surveillance should occur every 3-6 months along with surgical consultation for consideration of duodenectomy.[9]

Patients with advanced polyposis should be referred to expert centers to be managed by endoscopists with expertise in FAP.[9] Endoscopic treatment is used for downstaging, with the aim of delaying the development of stage 4 disease. Endoscopic therapies for duodenal adenomas include polypectomy, endoscopic mucosal resection, and ablation.[12]​

There is insufficient evidence for the benefit of chemoprevention in the management of duodenal polyps. Patients should be referred to expert centers for consideration of enrollment in a clinical trial if they are interested in chemoprevention. There are currently no approved drugs for the prevention or regression of duodenal adenomas.[9]

Management of attenuated FAP

Frequent colonoscopic adenoma clearance may be suitable for patients with a low polyp burden.[43][51][59][60][61]​ This is generally defined as having >20 adenomas (all <1 cm in diameter) with no advanced histology.[9] 

Where adenoma burden cannot be managed endoscopically, surgery should be offered. This is typically when polyp burden is >20 (at any individual exam), polyps have been previously ablated, some polyps are >1 cm in size, or advanced histology is noted in any polyp.[9]

Choice of surgery in attenuated FAP is individualized based on the age of the patient, their previous surgical history, location of polyps, and patient preferences.[51] In most cases, rectal adenomas are few, therefore colectomy with an IRA and continuous, lifelong surveillance of the rectum is the management of choice.

Chemoprevention

Chemoprevention may be considered as an adjunct in the management of retained rectum or ileal pouch in select patients with FAP/AFAP following prophylactic surgery.[9][28]​​ Available data suggest that sulindac is the most potent drug for polyp regression; however, it is not yet known whether decreases in polyp burden reduces colorectal cancer risk.[9][62]

Patients should be referred to expert centers for consideration of enrollment in a clinical trial if they are interested in chemoprevention. There are currently no approved drugs for this indication.

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