Pancreatic cancer surveillance not recommended for familial adenomatous polyposis: a fine and gray risk analysis

Abstract

Pancreatic cancer (PDAC) surveillance programs are recommended for individuals with a PDAC lifetime-risk ≥ 5% to improve outcomes. While familial adenomatous polyposis (FAP) is linked to increased PDAC risk, robust data to guide surveillance recommendations is lacking. This study evaluates PDAC risk in a large FAP-cohort.Data were collected from FAP cohorts in the United States (US) and the Netherlands (NL), including individuals (≥ 18 years) with a confirmed (likely) pathogenic APC variant. Cumulative PDAC incidence, adjusted for death as competing risk, was compared with control data from the Netherlands Cancer Registry and Statistics Netherlands. Data were collected from FAP cohorts in the United States (US) and the Netherlands (NL), including individuals (≥ 18 years) with a confirmed (likely) pathogenic APC variant. Cumulative PDAC incidence, adjusted for death as competing risk, was compared with control data from the Netherlands Cancer Registry and Statistics Netherlands. The US-cohort (n = 357) and NL-cohort (n = 1000) had a median age at the end of follow-up of 46 years (IQR, 32.0-60.0) and 60 years (IQR, 47.5-72.5), respectively. The cumulative risk of PDAC by age 70 was 1.3% (95% CI, 0.2-8.4) in the US cohort and 0.6% (95% CI 0.2-1.7) in the NL cohort. When combining both FAP-cohorts, the cumulative risk of PDAC by age 70 was 0.7% (95% CI, 0.3-1.8). For comparison, the cumulative incidence of PDAC in the general population at age 70 was 0.3% (95% CI 0.3-0.3), corresponding to a relative risk of 2.2 (95% CI, 0.9-5.7). Our findings indicate that PDAC risk in FAP patients is not statistically significantly higher than in the general population. As the cumulative incidence remains below the 5% threshold, PDAC surveillance is not recommended.