Cancer Incidence and Mortality in Familial Adenomatous Polyposis Syndrome

BACKGROUND: Risk-reducing colectomy in familial adenomatous polyposis syndrome is the standard of care. This has increased the importance of surveillance for extra-colonic malignancies in post-colectomy individuals. OBJECTIVE: We sought to define the present-day incidence of all cancers and mortality in familial adenomatous polyposis. DESIGN: Retrospective longitudinal cohort study. SETTINGS: Two large academic hospitals. PATIENTS: Eligible patients carried an APC pathogenic variant or met clinical criteria for familial adenomatous polyposis. MAIN OUTCOMES MEASURES: Cancer diagnosis, mortality, associated risk factors. RESULTS: A total of 358 patients were identified. The percentage who exhibited a classic familial adenomatous polyposis phenotype was 63.7%; 21.2% were de novo , and 82.7% had a colectomy. Colorectal cancer was the most common cancer (N = 59, 16.5%). Colorectal cancer diagnoses were associated with de novo familial adenomatous polyposis (odds ratio 7.8 [95% CI 3.51-17.35; p < 0.001]). Thyroid, duodenal/small bowel, gastric, and neuroendocrine tumors were reported in 7.5%, 3.1%, 2.8%, and 2.5% of patients, respectively. Rates of cancer were similar in classic and attenuated familial adenomatous polyposis. Thirty-nine patients (10.9%) died at a mean age of 49.6±17.1 years. Twenty-six deaths were malignancy-related, and colorectal cancer was the leading cause (N = 10). All colorectal cancer-related deaths occurred in individuals with classic familial adenomatous polyposis, and 9/10 were not previously diagnosed with the syndrome. Gastric and duodenal/small bowel cancer were the second leading causes (4 deaths each), and all occurred after colectomy. Fifty-nine percent of all deaths were attributable to a familial adenomatous polyposis-related malignancy or morbidity. LIMITATIONS: Retrospective clinical data. CONCLUSIONS: Colorectal cancer remains the most common malignancy and cause of death in familial adenomatous polyposis. However, nearly all colorectal cancer-related deaths occurred in individuals unaware of their familial adenomatous polyposis diagnosis, and none occurred in the attenuated syndrome. In patients who had a colectomy, gastric and duodenal/small bowel cancers are now the leading causes of death. See Video Abstract .