Life expectancy and changing causes of mortality in familial adenomatous polyposis (FAP)

BACKGROUND: The impact of modern management on life expectancy in familial adenomatous polyposis (FAP) remains sparsely reported, and recent treatment effects on disease-related causes of death are unclear. This study provides an updated assessment of life expectancy and mortality causes. METHODS: Patients born after January 1935 were identified from a prospectively maintained registry with supplementary clinical record review. Retrospective life table analysis compared mortality with a matched UK Office for National Statistics population. Causes of death were analysed by era and stratified by presentation type - newly presenting patients versus screen-detected relatives identified through family screening. RESULTS: Among 1917 patients with FAP, 364 deaths occurred versus 28 expected in the general population. Screen-detected relatives had consistently lower mortality, comparable to the general population (median SMR 0.66; SMR <1 throughout), whereas overall mortality was markedly higher in the unselected cohort (median SMR 11.09; p < 0.01). Newly presenting patients showed persistently elevated mortality across most birth cohorts.Colorectal disease remained the leading cause of death but declined significantly over time (64% pre-2001 to 31% post-2013; p < 0.01). Conversely, deaths from duodenal (3% to 12%; p < 0.01) and gastric disease (1% to 8%; p < 0.01), as well as non-FAP-related causes, increased. Screen-detected relatives had fewer colorectal deaths, particularly in earlier eras, but proportionally more duodenal and non-FAP-related deaths. CONCLUSION: Recent FAP cohorts now have mortality comparable to the general population. Although colorectal mortality has declined, gastroduodenal and non-FAP-related causes have increased, underscoring the need for continued surveillance and broader long-term management strategies.