Next-Generation Noninvasive Colorectal Cancer Screening

Noninvasive tests for colorectal cancer (CRC) screening in average-risk individuals continue to evolve, with the premise of increasing screening participation among eligible individuals. In addition to fecal immunochemical testing (FIT), which has become the noninvasive standard for which to improve sensitivity for detecting CRC and specificity for detecting the absence of CRC, new US Food and Drug Administration–approved tests include the detection of DNA in a next-generation multitarget stool DNA test, the detection of RNA in a multitarget stool RNA test, and blood tests that detect cell-free DNA for genomic alterations, fragmentations, and aberrant methylation, all of which have undergone large clinical trials for effectiveness. Each of these new tests improves upon the CRC sensitivity of FIT but not its specificity. Test sensitivity for CRC detection in persons <50 years of age is comparable to that in persons >50 years. Fecal tests with direct sampling of stool have improved sensitivity for advanced adenomas compared to FIT, but advanced adenoma sensitivity is regressed in blood tests compared to FIT. With about a third of the screening-eligible population not actively screened in the United States, the expansion of the screening-eligible population to include those >45 years of age, the disparity in some populations with lower-than-average screening rates, and the limited colonoscopy screening opportunities due to choice, schedule, availability, or pandemic interruption, these noninvasive tests may fill the gap and rectify CRC screening shortcomings and barriers that colonoscopy alone cannot fill.