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Fecal DNA Test Outperforms Fecal Occult Blood Test for Colorectal Cancer Screening

Fecal DNA testing is an option primarily for patients who are unwilling to undergo colonoscopy or for whom colonoscopy is unsafe.

Development of an effective, noninvasive colorectal cancer screening test has long been a priority. Although fecal DNA testing has shown potential in preliminary studies, the current report is the first large scale screening study among average-risk, asymptomatic individuals. The study was conducted at 81 U.S. sites and was sponsored by the developer of the fecal DNA test used in the study.

A total of 4404 subjects provided fecal samples for DNA analysis, completed nonrehydrated Hemoccult II cards for fecal occult blood testing (FOBT), and underwent colonoscopy. Fecal DNA analysis was performed on a subgroup of 2507 subjects, including all subjects with adenocarcinoma or advanced adenoma, plus randomly chosen subjects with no polyps, tubular adenomas <1 cm in diameter, or hyperplastic polyps. The DNA panel assessed point mutations in the adenomatous polyposis coli gene, p53 tumor suppressor gene, and K-ras oncogene, as well as the microsatellite instability marker BAT-26 and an assay for hyperamplifiable or "long" DNA.

Colonoscopy revealed 31 invasive cancers and 403 advanced adenomas. The DNA panel, compared to FOBT, detected a significantly greater proportion of invasive cancers (51.6% vs. 12.9%), invasive cancers plus adenomas with high-grade dysplasia (40.8% vs. 14.1%), and advanced neoplasia (adenoma 1 cm, villous histology, high-grade dysplasia, or cancer; 18.2% vs. 10.8%). Specificity, calculated in subjects with normal colonoscopies, was 94.4% for fecal DNA and 95.2% for FOBT.

Comment: In this study, a multitarget fecal DNA panel was more effective than a one-time nonrehydrated Hemoccult II test at detecting colorectal cancer plus adenomas with high-grade dysplasia. However, the sensitivity of the DNA panel was disappointing given the cost of the test, and questions remain about the panel's performance compared to that of rehydrated Hemoccult II, Hemoccult Sensa, immunochemical tests, or repeated annual testing with nonrehydrated Hemoccult II. Previous analyses (using more favorable assumptions about effectiveness than those used in this study) have shown that colonoscopy is superior to fecal DNA testing in both effectiveness and cost-effectiveness. Thus, fecal DNA testing is an option primarily for patients who are unwilling to undergo colonoscopy or for whom colonoscopy is unsafe. Preliminary results from an ongoing NIH trial suggest there is no value to performing extracolonic testing for cancer in asymptomatic people with positive fecal DNA tests. Whether those with positive fecal DNA tests and negative colonoscopy results should undergo repeat colonoscopy in 1 to 2 years remains uncertain. Despite these questions, the long-term outlook for fecal DNA testing is positive, given the potential for improvements in the technology.

— Douglas K. Rex, MD

Published in Journal Watch Gastroenterology January 19, 2005

Citation(s):

Imperiale TF et al. Fecal DNA versus fecal occult blood for colorectal-cancer screening in an average-risk population. N Engl J Med 2004 Dec 23; 351:2704-14.

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