Background/Aims: The purpose of this review is to clarify the place of new-technology stool tests in screening for colorectal neoplasia. Findings: New technologies have been based on blood and cellular products of neoplasia. Fecal occult blood tests (FOBTs) based on guaiac (i.e. GFOBTs) have been proved to be effective, but their impact on mortality is modest. When GFOBTs are reconfigured to provide improved sensitivity for cancer, their specificity often becomes unacceptable. Fecal immunochemical tests (FITs) targeting the human hemoglobin molecule have been shown to have better sensitivity for neoplasia without an unacceptable deterioration in specificity. The new stool-sampling technologies for FITs also improve population participation rates in screening. Most recently, quantitative FITs have become available; these provide flexibility for the end-user as a desired sensitivity: specificity ratio can be selected that is feasible in the context of available colonoscopic resources. A multi-target fecal DNA test, comprising a test for undegraded DNA and certain common mutations, was found more sensitive for cancer, but not for adenoma, than the early GFOBTs. A more recent version including an epigenetic marker for the vimentin gene has further improved sensitivity for cancer, but performance relative to GFOBT or FIT is not clear. These ‘fecal DNA tests’ have not proved to be more specific for neoplasia than tests that detect blood. Conclusions: FIT should replace GFOBT as the first test in two-step screening of large populations. It is not yet clear that tests targeting nonhemoglobin molecular events provide a clear advantage over FIT.
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