title: Fecal Immunochemical Tests Combined With Other Stool Tests for Colorectal Cancer and Advanced Adenoma Detection: A Systematic Review.
abstract: OBJECTIVE
  Despite moderate to high detection rates of fecal immunochemical tests (FITs) of colorectal cancer (CRC), detection of adenomas remains limited. Further stool tests exist, which are not used in routine practice, such as DNA or RNA markers and protein markers. We aimed at systematically investigating and summarizing evidence for diagnostic performance of combinations of FIT with other stool tests compared with FIT alone in early detection of CRC and its precursors.
  
  
  METHODS
  We systematically reviewed studies that evaluated FITs in combination with other stool tests and compared measures of diagnostic accuracy with and without additional stool tests. PubMed and Web of Science were searched from inception to May 2015. Reference lists of eligible studies were also screened. Two reviewers extracted data independently.
  
  
  RESULTS
  Some of the reports on DNA, RNA, or tissue tests, including tests based on DNA mutations, methylation, and integrity in selected genes as well as microRNA expression, showed some improvements of diagnostic test accuracy. In contrast, so far assessed stool protein markers did generally not lead to substantial improvements in performance of FIT when added to the latter. Many marker combinations were reported only in one study each, and few studies were conducted in a true screening setting.
  
  
  CONCLUSIONS
  Several stool markers show potential to improve performance of FITs. However, the results require confirmation in further studies, which should also evaluate the costs and cost-effectiveness of combined screening strategies.
authors.affiliation: German Cancer Research Center (DKFZ), Division of Clinical Epidemiology and Aging Research, Heidelberg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Niedermaier
authors.affiliation: German Cancer Research Center (DKFZ), Division of Clinical Epidemiology and Aging Research, Heidelberg, Germany.
authors.forename: Korbinian
authors.initials: K
authors.lastname: Weigl
authors.affiliation: German Cancer Research Center (DKFZ), Division of Clinical Epidemiology and Aging Research, Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hoffmeister
authors.affiliation: German Cancer Research Center (DKFZ), Division of Clinical Epidemiology and Aging Research, Heidelberg, Germany.|German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Division of Preventive Oncology, Heidelberg, Germany.|German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Brenner