Interval cancer risk after the upper age limit of screening has been reached: Informing risk stratification in FIT-based colorectal cancer screening

Upper age limits are currently fixed for all fecal immunochemical test (FIT)-based colorectal cancer (CRC) screening programs. A risk-stratified upper age limit may be beneficial. Therefore, we assessed differences in interval CRC risk among individuals who had reached the upper age limit of screening (75 years). Individuals with a negative FIT (<47 μg Hb/g feces) in the final round of the Dutch CRC screening program were selected from the national screening database and linked to the national cancer registry to identify CRCs diagnosed within 24 months (interval CRCs). Survival analyses assessed whether sex and last fecal hemoglobin (f-Hb) concentration were associated with interval CRC risk. A multivariable logistic regression assessed whether sex, last f-Hb concentration and screening round were associated with stage distribution (early vs. late). Last f-Hb concentrations were considered detectable when they were >0 μg Hb/g feces. Among 305,761 individuals with a complete follow-up (24 months), 661 were diagnosed with interval CRC (21.6 per 10,000 negative FITs). Individuals with detectable f-Hb (15%) were 5 times more likely to be diagnosed with interval CRC than those without (HR 4.87, 95%CI: 4.19-5.65). Moreover, their cancers were more often detected at a late stage compared to individuals without detectable f-Hb (OR 1.45, 95%CI: 1.06-2.01). Our results show that interval CRC risk among individuals aged ≥75 differs substantially by last f-Hb concentration, indicating a uniform age to stop screening is suboptimal. Future research, taking into account multiple screening rounds and FIT results, should determine the optimal risk-stratified screening strategy.