Personalized risk estimates of advanced neoplasia development in individuals with a family history of colorectal cancer.

To optimize surveillance in individuals with a family history (FH) of colorectal cancer (CRC), knowledge on the incidence rate of non-advanced adenomas (nAAs) and their progression rate to advanced neoplasia (AN) is crucial. We jointly estimated personalized adenoma incidence and progression rates using a novel statistical approach. We used data of individuals with ≥ 1 first-degree relative with CRC who underwent  ≥ 2 colonoscopies (n = 876 individuals; n = 2384 colonoscopies). Interval-censored data on timing and yield (no adenomas/nAA/AN) of each colonoscopy were available. nAA incidence and progression time from nAA to AN were estimated using a Bayesian progressive three-state model. Over a median follow-up of 6 years (interquartile range 5-6), 60 (6.8%) individuals developed AN (2 CRC, 58 AA) while 246 (28.1%) developed a nAA. The 5-year risk of developing nAA from baseline was estimated to be 29% (95% Crl: 21-39%). This risk was significantly associated with age and FH type. Estimated risk of progressing to AN within 5 years since nAA onset was 29% (95% Crl: 21-39%), and was significantly associated with having advanced adenomas at baseline. This resulted in a 5-year risk of transitioning from 'no adenomas' to AN of 7% (95% Crl: 5-9%). We showed that only 7% of individuals develop AN (primarily AAs) within the current 5-year colonoscopy surveillance interval. Future studies should evaluate whether this relatively low risk justifies slight extension of the surveillance interval or the use of fecal testing to guide colonoscopy timing. Furthermore, surveillance intensity could potentially be tailored based on age and FH.