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

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.

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.

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.

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.