Fecal Immunochemical Tests Combined With Other Stool Tests for Colorectal Cancer and Advanced Adenoma Detection: A Systematic Review

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Abstract

OBJECTIVES:

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.

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Most cited references 29

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Impact on colorectal cancer mortality of screening programmes based on the faecal immunochemical test.

Stefano Guzzinati, Susanna Baracco, Manuel Zorzi … (2015)

Colorectal cancer (CRC) screening programmes based on the guaiac faecal occult blood test (gFOBT) reduce CRC-specific mortality. Several studies have shown higher sensitivity with the faecal immunochemical test (FIT) compared with gFOBT. We carried out an ecological study to evaluate the impact of FIT-based screening programmes on CRC mortality. In the Veneto Region (Italy), biennial FIT-based screening programmes that invited 50-69-year-old residents were introduced in different areas between 2002 and 2009. We compared CRC mortality rates from 1995 to 2011 between the areas where screening started in 2002-2004 (early screening areas (ESA)) and areas that introduced the screening in 2008-2009 (late screening areas (LSA)) using Poisson regression models. We also compared available data on CRC incidence rates (1995-2007) and surgical resection rates (2001-2012). Before the introduction of screening, CRC mortality and incidence rates in the two areas were similar. Compared with 1995-2000, 2006-2011 mortality rates were 22% lower in the ESA than in the LSA (rate ratio (RR)=0.78; 95% CI 0.68 to 0.89). The reduction was larger in women (RR=0.64; CI 0.51 to 0.80) than in men (RR=0.87; CI 0.73 to 1.04). In the ESA, incidence and surgery rates peaked during the introduction of the screening programme and then returned to the baseline (2006-2007 incidence) or dropped below initial values (surgery after 2007). FIT-based screening programmes were associated with a significant reduction in CRC mortality. This effect took place much earlier than reported by gFOBT-based trials and observational studies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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Systematic reviews and meta-analyses of diagnostic test accuracy.

Mariska Leeflang (2014)

Systematic reviews of diagnostic test accuracy summarize the accuracy, e.g. the sensitivity and specificity, of diagnostic tests in a systematic and transparent way. The aim of such a review is to investigate whether a test is sufficiently specific or sensitive to fit its role in practice, to compare the accuracy of two or more diagnostic tests, or to investigate where existing variation in results comes from. The search strategy should be broad and preferably fully reported, to enable readers to assess the completeness of it. Included studies usually have a cross-sectional design in which the tests of interest, ideally both the index test and its comparator, are evaluated against the reference standard. They should be a reflection of the situation that the review question refers to. The quality of included studies is assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 checklist, containing items such as a consecutive and all-inclusive patient selection process, blinding of index test and reference standard assessment, a valid reference standard, and complete verification of all included participants. Studies recruiting cases separately from (healthy) controls are regarded as bearing a high risk of bias. For meta-analysis, the bivariate model or the hierarchical summary receiver operating characteristic model is used. These models take into account potential threshold effects and the correlation between sensitivity and specificity. They also allow addition of covariates for investigatation of potential sources of heterogeneity. Finally, the results from the meta-analyses should be explained and interpreted for the reader, to be well understood. © 2013 The Author Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

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Comparison of guaiac-based and quantitative immunochemical fecal occult blood testing in a population at average risk undergoing colorectal cancer screening.

Seungho Ryu, Young Hee Kim, Dong I L Park … (2010)

Although some studies have shown that the quantitative, immunochemical fecal occult blood test (FOBT) (qFIT) has better performance characteristics than the standard guaiac-based FOBT (GT) for identifying advanced colorectal neoplasia (ACRN), there is limited information on test performance of these tests in average-risk populations. Seven hundred seventy consecutive average-risk patients from four centers who were undergoing screening colonoscopy also provided stool samples. Stool specimens from three consecutive bowel movements were applied to a hemoccult II test card (Beckman Coulter, Fullerton, CA) and OC-SENSA MICRO (Eiken Chemical, Tokyo, Japan) sampling probes at the same time. We measured the diagnostic value of the qFIT for detecting an ACRN by using three criteria: sensitivity, specificity, and likelihood ratios. A receiver operating characteristic curve for determining the qFIT cutoff values and the number of tests that best discriminated between ACRNs and other findings were determined. Seventy-eight ACRNs were identified during colonoscopy. At all hemoglobin thresholds, the sensitivity of the qFIT was higher than that of the GT for cancer or ACRN. The sensitivity and specificity of the GT for detecting advanced adenomas, cancer, and ACRNs were 13.6%/92.4%, 30.8%/92.4%, and 16.7%/92.9%, respectively. Using the 100 ng/ml cut point and three-sample qFIT results, the sensitivity and specificity of the qFIT for detecting advanced adenomas, cancer, and ACRNs were 33.9%/90.6%, 84.6%/89.8%, and 43.7%/91.9%, respectively. The area under the curve for cancer indicated that using either 2 or 3 tests provided the best discrimination for cancer. The qFIT provides a higher sensitivity for detecting ACRN and cancer than the GT, and has an acceptable specificity that significantly reduces the need for colonoscopic evaluation in the screened population.

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Author and article information

Journal

Journal ID (nlm-ta): Clin Transl Gastroenterol

Journal ID (iso-abbrev): Clin Transl Gastroenterol

Title: Clinical and Translational Gastroenterology

Publisher: Nature Publishing Group

ISSN (Electronic): 2155-384X

Publication date (Print): June 2016

Publication date (Electronic): 02 June 2016

Publication date PMC-release: 1 June 2016

Volume: 7

Issue: 6

Page: e175

Affiliations

[1 ]German Cancer Research Center (DKFZ), Division of Clinical Epidemiology and Aging Research , Heidelberg, Germany

[2 ]German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Division of Preventive Oncology , Heidelberg, Germany

[3 ]German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ) , Heidelberg, Germany

Author notes

[* ]German Cancer Research Center (DKFZ), Division of Clinical Epidemiology and Aging Research , Im Neuenheimer Feld 581, Heidelberg D-69120, Germany. E-mail: h.brenner@ 123456dkfz.de

Article

Publisher Item ID: ctg201629

DOI: 10.1038/ctg.2016.29

PMC ID: 4931594

PubMed ID: 27253514

SO-VID: 83b4a9d2-c1aa-4f33-82f8-7a719f3e43f4

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Clinical and Translational Gastroenterology is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/

Fecal Immunochemical Tests Combined With Other Stool Tests for Colorectal Cancer and Advanced Adenoma Detection: A Systematic Review

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Abstract

OBJECTIVES:

METHODS:

RESULTS:

CONCLUSIONS:

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Karger: Gastroenterology

Most cited references 29

Impact on colorectal cancer mortality of screening programmes based on the faecal immunochemical test.

Systematic reviews and meta-analyses of diagnostic test accuracy.

Comparison of guaiac-based and quantitative immunochemical fecal occult blood testing in a population at average risk undergoing colorectal cancer screening.

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