QS136 - Trends in Cause of Death Among Patients with Familial Adenomatous Polyposis Syndrome

Purpose/Background: Common causes of death among patients with familial adenomatous polyposis syndrome (FAP) include colorectal cancer, duodenal cancer, and desmoid disease. We hypothesized that advances in management of FAP-associated cancers has reduced colorectal and duodenal cancer-related deaths and increased lifespan among patients with FAP. Our study objectives were to characterize causes of death and identify temporal and generational trends in cause of death and lifespan among patients with FAP.

Methods/Interventions: A single-institution, prospective hereditary gastrointestinal cancer registry created in 1979 was queried for patients with FAP who had died. Causes of death were determined through medical record review and information provided by family members. Causes of death were classified as cancer (colorectal, gastric, duodenal/small bowel, other/unknown), desmoid disease, or unrelated to cancer or desmoids. Descriptive statistics were generated to assess temporal changes in cause of death and lifespan. Multivariable logistic regression was utilized to assess the association between year of death, presence of a de novo mutation and cause of death.

Results/Outcomes: A total of 184 patients who died between 1979 and 2023 were identified. The mean age at death was 49.2 (SD 15.5) years, 50.5% were female, and 19.6% had a de novo mutation. The cause of death was colorectal cancer in 30.4% of patients (18.5% colon; 12.0% rectum), gastric cancer in 5.4%, duodenal/small bowel cancer in 8.7%, other cancers in 14.1%, desmoid disease in 17.4%, and death was unrelated to cancer or desmoid disease in 23.9%. Colorectal cancer deaths decreased over time (Figure; 1979-1995: 44.9%; 1995-2009: 30.4%; 2010-2023: 21.5%; OR 0.97 per year [95% CI 0.94-1.00]; p=0.02) while deaths from gastric cancer (1979-1995: 0%; 1995-2009: 0%; 2010-2023: 12.7%; OR 1.22 [95% CI 1.06-1.41]; p=0.005) and deaths unrelated to cancer or desmoid disease (1979-1995: 12.2%; 1995-2009: 23.2%; 2010-2023: 31.7%; OR 1.03 [95% CI 1.01-1.07]; p=0.02) increased. Deaths attributable to desmoid disease did not change (OR 1.03 [95% CI 0.97-1.03], p=0.95). Presence of a de novo mutation was associated with an increased likelihood of death from colorectal cancer (47.2% vs. 29.2%, OR 2.37 [95% CI 1.06-5.29], p=0.04) and with a decreased likelihood of death unrelated to cancer or desmoid disease (5.6% vs. 30.0%, OR 0.15 [95% CI 0.03-0.65], p=0.01). The mean age at death did not change (1979-1995: 47.4 [SD 14.1] years; 1995-2009: 48.3 [SD 14.9] years; 2010-2023: 47.9 [SD 16.7] years; p=0.26).

Conclusion/Discussion: Over 45 years, colorectal cancer deaths decreased among patients with FAP in a hereditary cancer registry while deaths from gastric cancer and non-FAP associated causes increased; however, this did not result in improved lifespan. Desmoid-related deaths remained stable and are the second-leading FAP-related cause of death in our study population. This study suggests that improved identification and management of FAP-related tumors may be reducing colorectal cancer deaths but that other causes of death, particularly desmoid disease and gastric cancer, must be addressed.