Fecal DNA Testing for Colorectal Cancer Screening

Abstract

Fecal (or stool) DNA examination is a noninvasive strategy recommended by several medical professional societies for colorectal cancer (CRC) screening in average-risk individuals. Fecal DNA tests assay stool for human DNA shed principally from the colon. Colonic lesions such as adenomatous and serrated polyps and cancers exfoliate cells containing neoplastically altered DNA that may be detected by sensitive assays that target specific genetic and epigenetic biomarkers to discriminate neoplastic lesions from non-neoplastic tissue. Cross-sectional validation studies confirmed initial case-control studies' assessment of performance of an optimized multitarget stool DNA (mt-sDNA) test, leading to approval by the US Food and Drug Administration in 2014. Compared to colonoscopy, mt-sDNA showed sensitivity of 92% for detection of CRC, much higher than the 74% sensitivity of another recommended noninvasive strategy, fecal immunochemical testing (FIT). Detections of advanced adenomas and sessile serrated polyps were higher with mt-sDNA than FIT (42% versus 24% and 42% versus 5%, respectively), but overall specificity for all lesions was lower (87% versus 95%). The mt-sDNA test increases patient life-years gained in CRC screening simulations, but its cost relative to other screening strategies needs to be reduced by 80-90% or its sensitivity for polyp detection enhanced to be cost effective. Noninvasive CRC screening strategies such as fecal DNA, however, have the potential to significantly increase national screening rates due to their noninvasive nature and convenience for patients.