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Multitarget stool DNA testing increased colorectal cancer detection
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Multitarget stool DNA testing demonstrated an increased rate of colorectal cancer detection compared with fecal immunochemical testing, according to study results.
However, the DNA test had lower specificity and thus a higher rate of false-positive results than that associated with fecal immunochemical tests (FIT).
Thomas F. Imperiale
Thomas F. Imperiale, MD, of the department of medicine at the Indiana University School of Medicine, and colleagues evaluated data from 9,989 adults considered to have an average risk for colorectal cancer. Colonoscopy identified 757 patients with advanced precancerous lesions — defined as advanced adenomas or sessile serrated polyps at least 1 cm in the greatest dimension — and 65 patients with colorectal cancer.
The multitarget stool DNA testing detected 60 of the 65 colorectal cancers, whereas FIT detected 48. Researchers calculated a 92.3% (95% CI, 83-97.5) sensitivity with multitarget stool DNA testing, which was significantly higher than the 73.8% (95% CI, 61.5-84) sensitivity associated with FIT (P=.002).
The DNA test also demonstrated significantly increased sensitivity for the detection of advanced precancerous lesions compared with FIT (42.4% vs. 23.8%; P˂.001).
More polyps with high-grade dysplasia (69.4% vs. 46.2%; P=.004) and serrated sessile polyps ≥1 cm (42.4% vs. 5.1%; P˂.001) were detected with the DNA test than with FIT.
However, the multitarget stool DNA test demonstrated reduced specificity among patients with nonadvanced or negative findings (86.6% vs. 94.9%; P˂.001) and those with negative colonoscopy results (89.8% vs. 96.4%; P˂.001) compared with FIT.
Overall, researchers found the number of adults needed to be screened to detect one case of colorectal cancer was 154 with colonoscopy, 166 with DNA testing and 208 with FIT.
Due to limitations such as the increased false-positive rate and problems collecting samples (6.3% vs. 0.3%), more data are needed to assess the applicability of the DNA test, Douglas J. Robertson, MD, MPH, of the Geisel School of Medicine at Dartmouth, and Jason A. Dominitz, MD, MHS, of the University of Washington School of Medicine, wrote in an accompanying editorial.
“The new multitarget stool DNA test is clearly an improvement over its predecessors, and the result of this study will help to inform the current effort of the US Preventive Services Task Force to re-evaluate screening tests,” Robertson and Dominitz wrote. “Only through a 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.”
For more information:
- Imperiale TF. N Engl J Med. 2014;doi:10.1056/NEJMoa1311194.
- Robertson DJ. N Engl J Med. 2014;doi:10.1056/NEJMe1400092.
Disclosure: See the study for a full list of the researchers’ relevant financial disclosures.
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Richard M. Goldberg, MD
Imperiale and colleagues tested about 10,000 patients with standard fecal immune testing (FIT) and an experimental fecal multitarget DNA assay plus human hemoglobin immunoassay prior to colonoscopy, comparing the specificity and sensitivity of two noninvasive screening strategies.
Colonoscopy identified 65 colorectal cancers and 757 advanced precancerous lesions.
DNA testing was significantly more sensitive and specific in detecting cancer and advanced neoplasia, but more commonly was falsely positive. Over 15 years, Mayo Clinic researchers and the sponsor, Exact Sciences, improved the sample storage buffer, identified more discriminating genetic markers, honed in on human DNA in the stool and optimized the analytic methodology.
Clearly, this technique has a performance advantage over FIT and a convenience advantage over colonoscopy. These investigators deserve credit for finding a stool-based screening technology using molecular genetics in a milieu where the prevalence of bacterial DNA vastly exceeds pathological human DNA. Its noninvasive nature means repetitive testing after initially negative results could enhance performance, a strategy that would need to be further compared with respect to outcome and costs with serial FIT and other techniques. The FDA is determining suitability of the assay for commercial use.
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