Multitarget stool DNA for colorectal cancer screening: A review and commentary on the United States Preventive Services Draft Guidelines

Abstract

Multitarget stool DNA (mt-sDNA) testing was approved for average risk colorectal cancer (CRC) screening by the United States Food and Drug Administration and thereafter reimbursed for use by the Medicare program (2014). The United States Preventive Services Task Force (USPSTF) October 2015 draft recommendation for CRC screening included mt-sDNA as an “alternative” screening test that “may be useful in select clinical circumstances”, despite its very high sensitivity for early stage CRC. The evidence supporting mt-sDNA for routine screening use is robust. The clinical efficacy of mt-sDNA as measured by sensitivity, specificity, life-years gained (LYG), and CRC deaths averted is similar to or exceeds that of the other more specifically recommended screening options included in the draft document, especially those requiring annual testing adherence. In a population with primarily irregular screening participation, tests with the highest point sensitivity and reasonable specificity are more likely to favorably impact CRC related morbidity and mortality than those depending on annual adherence. This paper reviews the evidence supporting mt-sDNA for routine screening and demonstrates, using USPSTF’s modeling data, that mt-sDNA at three-year intervals provides significant clinical net benefits and fewer complications per LYG than annual fecal immunochemical testing, high sensitivity guaiac based fecal occult blood testing and 10-year colonoscopy screening.

Keywords: Colorectal cancer screening, Multitarget stool DNA, Stool DNA, The United States Preventive Services Task Force, Cancer Intervention Surveillance Modeling Network, Fecal immunological technique, Modeling, Interval

Core tip: Multi-target stool DNA (mt-sDNA) testing was approved for average risk colorectal cancer (CRC) screening by the United States Food and Drug Administration (2014). The evidence supporting mt-sDNA for routine screening use is robust. The clinical efficacy of mt-sDNA every three years, measured by life-years gained, and CRC deaths averted, is similar to that of other screening strategies more specifically recommended by the United States Preventive Services Task Force. In an irregularly screened population, however, tests with the highest point sensitivity and reasonable specificity like mt-sDNA are more likely to reduce CRC related morbidity and mortality than less sensitive tests that depend on annual adherence to achieve high programmatic sensitivity.