Interval Cancers Are More Deadly Than Screen-Detected Cancers but Are Not Different in Molecular Features

Previous studies have found that interval or postcolonoscopy cancers have molecular profiles that differ somewhat from those of cancers detected at a baseline colonoscopy, including increased frequency of microsatellite instability and hypermethylation, suggesting that serrated lesions account disproportionately for interval cancers. 

This study examined mortality and molecular features in screen-detected versus interval cancers in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial in the U.S. and validated findings with the Nurses’ Health Study (NHS) and Health Professionals Follow-up Study (HPFS). Of 1175 cases of colorectal cancer (CRC) in the PLCO trial, 182 (15%) were interval. Of 3661 cases of CRC in the NHS and HPFS, 514 (14%) were interval cancers. 

In a multivariable analysis, CRC-specific mortality was higher with interval cancers (hazard ratio [HR], 1.57) in the PLCO trial and 1.45 in the NHS and HPFS. Overall mortality was also higher, with HRs of 1.38 and 1.24, respectively. There were no differences between interval and screen-detected cancers in molecular features, though BRAF mutations were numerically more common in interval cancers (26% vs 14%).