Cancer Risks in Familial Adenomatous Polyposis

Timothy Yen, MD

Assistant Professor, Loma Linda University Health, Loma Linda, CA

This article reviews Beck SH, et al. Cancer risks in attenuated and classical familial adenomatous polyposis: A nationwide cohort with matched, nonexposed individuals. Am J Gastroenterol. 2025;120(6):1345-1352.

Access the article through The American Journal of Gastroenterology

Keywords: FAP, cancer, risk, genetics

COMMENTARY

Why Is This Important?
FAP is a difficult population to study because it is relatively rare, although it’s clinical presentation is quite dramatic due to the burden of colorectal polyps. Many studies on FAP harken back to historical studies before the advent of routine high-definition colonoscopies for screening, as reflected in the increasing incidence of aFAP over time.¹ It is thus helpful to have a more contemporary description of cancer risks and outcomes in both cFAP and aFAP.

Key Study Findings

There is still a subset of FAP patients that can develop rectal cancer after colectomy, thus frequent flexible sigmoidoscopy of the residual rectum (typically every 6-12 months depending on polyp burden) remains important.² The burden of duodenal adenomas is still substantial, particularly in the cFAP population, although we still do not fully understand risk factors for duodenal adenocarcinoma otherwise.

Caution
This study does not account for surveillance procedures such as colonoscopy prior to colectomy, as well as surveillance flexible sigmoidoscopy/pouchoscopy (for those with an ileorectal anastomosis or ileo-anal pouch anastomosis) or ileoscopy (for those with an end ileostomy) after colectomy. Prior studies have observed that the risk of ileal adenomas is higher in those with a pouch compared to end ileostomy, which would be an important risk factor to understand given its potential impact on choice of surgery.³ It is also curious that only about half of patients underwent surgery, which may be from inadequate observation time (i.e. the colectomy has not happened) rather than non-operative colonoscopic management of polyp burden, which is seldomly feasible with substantial resource and colonoscopic burden.⁴

FAP patients are not typically recognized as high risk for pancreatic adenocarcinoma in national guidelines.^5-7 As the authors note, these patients did not undergo genetic re-evaluation to assess for comorbid pathogenic variants. To recognize this as a FAP-associated cancer, future studies must account for differences in other risk factors for pancreatic cancer (alcohol, tobacco, chronic pancreatitis etc.). Finally, the study did not examine desmoid disease, which is a leading cause of morbidity and mortality in FAP patients despite its non-malignant nature.

My Practice
Upon meeting a newly diagnosed FAP patient, I counsel the patient that although the risk of colorectal cancer is high, the risk can be dramatically reduced with colectomy and subsequent frequent lower endoscopies. Prior to colectomy, I find that the removal of most diminutive/small adenomas and counting the exact number of polyps is practically less useful. Given that the majority of FAP patients require extended or total colectomy, I perform colonoscopy with several diagnostic goals in mind: 1) masses concerning for cancer or advanced polyps; 2) estimating whether the rectal burden of polyps is “endoscopically manageable” over time with repeat procedures; 3) define the anatomic extent of endoscopically “un-manageable” polyposis in collaboration with colorectal surgery to inform whether the patient is a candidate for an ileorectal or even ileosigmoid anastomosis to improve post-operative quality of life. Finally, I do stress to the patient that even after surgery, frequent lower endoscopies are still critical to avoid the risk of rectal cancer.

For Future Research
Larger studies incorporating endoscopic data is still needed to understand how to manage the upper intestinal manifestations of FAP such as duodenal or gastric neoplasia, as well as medication interventions to help manage those with advanced duodenal neoplasia given the morbidity associated with duodenectomy.

Conflict of Interest
No conflicts of interest.

REFERENCES 

1. Yen T, Stanich PP, Axell L, et al. APC-Associated Polyposis Conditions. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, eds. GeneReviews. Seattle (WA): University of Washington, Seattle, WA.
2. Hodan R, Gupta S, Weiss JM, et al. Genetic/familial high-risk assessment: Colorectal, endometrial, and gastric, version 3.2024, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 2024;22:695-711.
3. Aelvoet AS, Roos VH, Bastiaansen BAJ, et al. Development of ileal adenomas after ileal pouch-anal anastomosis versus end ileostomy in patients with familial adenomatous polyposis. Gastrointestinal Endoscopy 2023;97:69-77.e1.
4. Ishikawa H, Yamada M, Sato Y, et al. Intensive endoscopic resection for downstaging of polyp burden in patients with familial adenomatous polyposis (J-FAPP Study III): a multicenter prospective interventional study. Endoscopy 2023;55:344-352.
5. Sawhney MS, Calderwood AH, Thosani NC, et al. ASGE guideline on screening for pancreatic cancer in individuals with genetic susceptibility: summary and recommendations. Gastrointest Endosc 2022;95:817-826.
6. Daly MB, Pal T, Maxwell KN, et al. NCCN guidelines insights: Genetic/familial high-risk assessment: Breast, ovarian, and pancreatic, version 2.2024. J Natl Compr Canc Netw 2023;21:1000-1010.
7. Aslanian HR, Lee JH, Canto MI. AGA clinical practice update on pancreas cancer screening in high-risk individuals: Expert review. Gastroenterology 2020;159:358-362.

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