| Summary: | OBJECTIVE: We conducted this systematic review to support the U.S. Preventive Services Task Force in updating its recommendation on screening for colorectal cancer (CRC). Our review addresses the effectiveness of CRC screening, the test accuracy of CRC screening modalities, and the harms of CRC screening. CONCLUSIONS: Since the 2016 USPSTF recommendation, there is more evidence on effectiveness and test accuracy of newer stool tests (FIT and sDNA-FIT), and the test accuracy of a serum test FDA approved for use in persons declining colonoscopy, FS, gFOBT, or FIT. We also identified a new metabolomic urine test with only one small study with test accuracy data, thus far limited to detection of adenomas. We also have more data on colonoscopy harms demonstrating higher estimates of major bleeding than previously described in 2016. Currently used screening modalities, including colonoscopy, FS, CTC, and various high-sensitivity stool-based tests, and a serum-based test each have different levels of evidence to support their use, different test performance to detect cancer and precursor lesions, and different risks of harms. Recommendations regarding which screening tests to use, or if there is a hierarchy of preferred screening tests, will depend on the decisionmaker's criteria for sufficiency of evidence and weighing the net benefit
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