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A noninvasive, multitarget stool DNA test detected significantly more cancer than did a fecal immunochemical test in people at average risk for colorectal cancer, but had greater false positive results, according to a report published March 19 in the New England Journal of Medicine.
The study’s primary outcome was the ability of the DNA test to detect colorectal cancer. The secondary outcome was the DNA test’s ability to detect advanced precancerous lesions, including advanced adenomas and sessile serrated polyps measuring 1 cm or more in diameter, compared with the performance of a commercially available fecal immunochemical test (FIT) for human hemoglobin.
The multitarget stool DNA test includes molecular assays for aberrantly methylated BMP3 and NDRG4 promoter regions, KRAS mutations, and beta-actin (a reference gene for human DNA quantity), as well as an immunochemical assay for human hemoglobin.
The study investigators enrolled 12,776 asymptomatic persons aged 50-84 years who were scheduled to undergo a colonoscopy screening; of those participants, 9,989 could be fully evaluated. The study took place in 90 sites in the United States and Canada from June 2011 to November 2012, led by Dr. Thomas F. Imperiale from Indiana University, Indianapolis, and his associates.
The DNA test’s sensitivity was greater than FIT was for the detection of colorectal cancer (92.3% vs. 73.8%, respectively) and for advanced precancerous lesions (42.4% vs. 23.8%, respectively), the investigators reported (N. Engl. J. Med. 2014 March 19 [doi:10.1056/NEJMoa1311194]). The difference could be from the DNA marker and algorithm components of the test, they noted, because both the DNA and FIT tests use almost identical hemoglobin immunoassay components.
The DNA test’s sensitivity for the detection of advanced precancerous lesions was approximately half that for the detection of colorectal cancer. DNA testing was more sensitive than was FIT for the detection of lesions with high-grade dysplasia (69.2% vs. 46.2%; P = .004) and sessile serrated polyps 1 cm or larger (42.4% vs. 5.1%; P less than .001), and for the detection of advanced precancerous lesions within the size ranges observed, the investigators reported.
However, FIT was more specific for the detection of both colorectal cancer and advanced precancerous lesions, by absolute differences of 6.6%-8.3%, the authors noted.
"A noninvasive test with a high single-application sensitivity for curable-stage cancer may provide an option for persons who prefer noninvasive testing," the investigators concluded. However, "questions about testing intervals and tailoring require further consideration."
Exact Sciences funded the study. Dr. Imperiale reported receiving grant support from Exact Sciences.
There has been substantial work to improve the sensitivity of DNA stool testing over the years, and while it has been "markedly improved, some caveats are worthy to note," said Dr. Douglas J. Robertson and Dr. Jason A. Dominitz.
The number of participants in the study who were excluded because of problems with sample collection or assay application was greater in the stool DNA group than in the FIT group. Because colorectal cancer was detected in 1 of the 154 participants on colonoscopy, possibly four cancers would have been missed because of the test’s complexity, they said.
Also, "given the lower specificity and greater expense of stool DNA testing as compared with FIT, it is unlikely that the test would be performed annually in the way FIT testing is recommended."
However, the new multitarget stool DNA test is an improvement over previous tests, Dr. Robertson and Dr. Dominitz noted, and the study results will help the U.S. Preventive Services Task Force reevaluate screening tests. They also called for comparative effectiveness studies to clarify the role of DNA testing.
"Only through better understanding of other key factors, such as the screening interval, adherence, cost, and diagnostic evaluation of positive results, can we determine the appropriate place for stool DNA testing on the screening menu," they concluded.
Dr. Robertson is with the White River Junction (Vt.) Veterans Affairs Medical Center and the Geisel School of Medicine at Dartmouth, Hanover, N.H. He reported receiving funding from Given Imaging. Dr. Dominitz is with the VA Puget Sound Health Care System and the University of Washington, Seattle; he reported no relevant disclosures. These remarks were taken from an editorial accompanying Dr. Imperiale’s report (N. Engl. J. Med. 2014 March 19 [doi:10.1056/NEJMe1400092]).
There has been substantial work to improve the sensitivity of DNA stool testing over the years, and while it has been "markedly improved, some caveats are worthy to note," said Dr. Douglas J. Robertson and Dr. Jason A. Dominitz.
The number of participants in the study who were excluded because of problems with sample collection or assay application was greater in the stool DNA group than in the FIT group. Because colorectal cancer was detected in 1 of the 154 participants on colonoscopy, possibly four cancers would have been missed because of the test’s complexity, they said.
Also, "given the lower specificity and greater expense of stool DNA testing as compared with FIT, it is unlikely that the test would be performed annually in the way FIT testing is recommended."
However, the new multitarget stool DNA test is an improvement over previous tests, Dr. Robertson and Dr. Dominitz noted, and the study results will help the U.S. Preventive Services Task Force reevaluate screening tests. They also called for comparative effectiveness studies to clarify the role of DNA testing.
"Only through better understanding of other key factors, such as the screening interval, adherence, cost, and diagnostic evaluation of positive results, can we determine the appropriate place for stool DNA testing on the screening menu," they concluded.
Dr. Robertson is with the White River Junction (Vt.) Veterans Affairs Medical Center and the Geisel School of Medicine at Dartmouth, Hanover, N.H. He reported receiving funding from Given Imaging. Dr. Dominitz is with the VA Puget Sound Health Care System and the University of Washington, Seattle; he reported no relevant disclosures. These remarks were taken from an editorial accompanying Dr. Imperiale’s report (N. Engl. J. Med. 2014 March 19 [doi:10.1056/NEJMe1400092]).
There has been substantial work to improve the sensitivity of DNA stool testing over the years, and while it has been "markedly improved, some caveats are worthy to note," said Dr. Douglas J. Robertson and Dr. Jason A. Dominitz.
The number of participants in the study who were excluded because of problems with sample collection or assay application was greater in the stool DNA group than in the FIT group. Because colorectal cancer was detected in 1 of the 154 participants on colonoscopy, possibly four cancers would have been missed because of the test’s complexity, they said.
Also, "given the lower specificity and greater expense of stool DNA testing as compared with FIT, it is unlikely that the test would be performed annually in the way FIT testing is recommended."
However, the new multitarget stool DNA test is an improvement over previous tests, Dr. Robertson and Dr. Dominitz noted, and the study results will help the U.S. Preventive Services Task Force reevaluate screening tests. They also called for comparative effectiveness studies to clarify the role of DNA testing.
"Only through better understanding of other key factors, such as the screening interval, adherence, cost, and diagnostic evaluation of positive results, can we determine the appropriate place for stool DNA testing on the screening menu," they concluded.
Dr. Robertson is with the White River Junction (Vt.) Veterans Affairs Medical Center and the Geisel School of Medicine at Dartmouth, Hanover, N.H. He reported receiving funding from Given Imaging. Dr. Dominitz is with the VA Puget Sound Health Care System and the University of Washington, Seattle; he reported no relevant disclosures. These remarks were taken from an editorial accompanying Dr. Imperiale’s report (N. Engl. J. Med. 2014 March 19 [doi:10.1056/NEJMe1400092]).
A noninvasive, multitarget stool DNA test detected significantly more cancer than did a fecal immunochemical test in people at average risk for colorectal cancer, but had greater false positive results, according to a report published March 19 in the New England Journal of Medicine.
The study’s primary outcome was the ability of the DNA test to detect colorectal cancer. The secondary outcome was the DNA test’s ability to detect advanced precancerous lesions, including advanced adenomas and sessile serrated polyps measuring 1 cm or more in diameter, compared with the performance of a commercially available fecal immunochemical test (FIT) for human hemoglobin.
The multitarget stool DNA test includes molecular assays for aberrantly methylated BMP3 and NDRG4 promoter regions, KRAS mutations, and beta-actin (a reference gene for human DNA quantity), as well as an immunochemical assay for human hemoglobin.
The study investigators enrolled 12,776 asymptomatic persons aged 50-84 years who were scheduled to undergo a colonoscopy screening; of those participants, 9,989 could be fully evaluated. The study took place in 90 sites in the United States and Canada from June 2011 to November 2012, led by Dr. Thomas F. Imperiale from Indiana University, Indianapolis, and his associates.
The DNA test’s sensitivity was greater than FIT was for the detection of colorectal cancer (92.3% vs. 73.8%, respectively) and for advanced precancerous lesions (42.4% vs. 23.8%, respectively), the investigators reported (N. Engl. J. Med. 2014 March 19 [doi:10.1056/NEJMoa1311194]). The difference could be from the DNA marker and algorithm components of the test, they noted, because both the DNA and FIT tests use almost identical hemoglobin immunoassay components.
The DNA test’s sensitivity for the detection of advanced precancerous lesions was approximately half that for the detection of colorectal cancer. DNA testing was more sensitive than was FIT for the detection of lesions with high-grade dysplasia (69.2% vs. 46.2%; P = .004) and sessile serrated polyps 1 cm or larger (42.4% vs. 5.1%; P less than .001), and for the detection of advanced precancerous lesions within the size ranges observed, the investigators reported.
However, FIT was more specific for the detection of both colorectal cancer and advanced precancerous lesions, by absolute differences of 6.6%-8.3%, the authors noted.
"A noninvasive test with a high single-application sensitivity for curable-stage cancer may provide an option for persons who prefer noninvasive testing," the investigators concluded. However, "questions about testing intervals and tailoring require further consideration."
Exact Sciences funded the study. Dr. Imperiale reported receiving grant support from Exact Sciences.
A noninvasive, multitarget stool DNA test detected significantly more cancer than did a fecal immunochemical test in people at average risk for colorectal cancer, but had greater false positive results, according to a report published March 19 in the New England Journal of Medicine.
The study’s primary outcome was the ability of the DNA test to detect colorectal cancer. The secondary outcome was the DNA test’s ability to detect advanced precancerous lesions, including advanced adenomas and sessile serrated polyps measuring 1 cm or more in diameter, compared with the performance of a commercially available fecal immunochemical test (FIT) for human hemoglobin.
The multitarget stool DNA test includes molecular assays for aberrantly methylated BMP3 and NDRG4 promoter regions, KRAS mutations, and beta-actin (a reference gene for human DNA quantity), as well as an immunochemical assay for human hemoglobin.
The study investigators enrolled 12,776 asymptomatic persons aged 50-84 years who were scheduled to undergo a colonoscopy screening; of those participants, 9,989 could be fully evaluated. The study took place in 90 sites in the United States and Canada from June 2011 to November 2012, led by Dr. Thomas F. Imperiale from Indiana University, Indianapolis, and his associates.
The DNA test’s sensitivity was greater than FIT was for the detection of colorectal cancer (92.3% vs. 73.8%, respectively) and for advanced precancerous lesions (42.4% vs. 23.8%, respectively), the investigators reported (N. Engl. J. Med. 2014 March 19 [doi:10.1056/NEJMoa1311194]). The difference could be from the DNA marker and algorithm components of the test, they noted, because both the DNA and FIT tests use almost identical hemoglobin immunoassay components.
The DNA test’s sensitivity for the detection of advanced precancerous lesions was approximately half that for the detection of colorectal cancer. DNA testing was more sensitive than was FIT for the detection of lesions with high-grade dysplasia (69.2% vs. 46.2%; P = .004) and sessile serrated polyps 1 cm or larger (42.4% vs. 5.1%; P less than .001), and for the detection of advanced precancerous lesions within the size ranges observed, the investigators reported.
However, FIT was more specific for the detection of both colorectal cancer and advanced precancerous lesions, by absolute differences of 6.6%-8.3%, the authors noted.
"A noninvasive test with a high single-application sensitivity for curable-stage cancer may provide an option for persons who prefer noninvasive testing," the investigators concluded. However, "questions about testing intervals and tailoring require further consideration."
Exact Sciences funded the study. Dr. Imperiale reported receiving grant support from Exact Sciences.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Major finding: A multitarget stool DNA test had significantly greater sensitivity than did a fecal immunochemical test for the detection of colorectal cancer (92.3% vs. 73.8%).
Data source: A cross-sectional prospective study of 9,989 asymptomatic patients aged 50-84 years.
Disclosures: Exact Sciences funded the study. Dr. Imperiale reported receiving grant support from Exact Sciences.
