DNA Stool Test Boosts Colorectal Cancer Screening Sensitivity

Colorectal screening sensitivity may be improved by use of a multitarget DNA stool test

medwireNews: Multitarget DNA stool testing offers a non-invasive option for colorectal cancer (CRC) screening with greater sensitivity than is achieved using the faecal Immunohistochemistry test (FIT), research shows.

When used to screen 9,989 asymptomatic patients aged 50 to 84 years old, the DNA stool test was 92.3% sensitive for CRC compared with just 73.8% for a commercially available FIT test using a haemoglobin threshold of 100 ng/mL, a significant difference.

The DNA stool test also showed significantly greater sensitivity than FIT for advanced precancerous lesions (42.4 vs 23.8%), high-grade dysplasia polyps (69.2 vs 46.2%) and serrated sessile polyps of 1 cm or larger in diameter (42.4 vs 5.1%).

As reported in The New England Journal of Medicine, the DNA stool test, which is not yet commercially available, screens for K-ras mutations, aberrant methylation of promoter regions of NDRG4 and BMP3 methylation, and beta-actin, as well as a haemoglobin immunoassay.

Overall, screening colonoscopy identified CRC in 0.7% of patients and advanced precancerous lesions in 6.7% of the group. The number needed to test to identify one CRC would be 166 using the DNA stool test compared with 154 patients with colonoscopy and 208 patients with FIT, say Thomas Imperiale, from Indiana University in Indianapolis, USA, and co-authors.

However, the DNA stool test was significantly less specific for CRC detection than FIT, at 86.6% versus 94.9% for patients with non-advanced adenomas or negative testing, and 89.8% versus 96.4% compared with a negative colonoscopy.

The researchers note that specificity of the DNA stool test for patients with diagnoses other than advanced neoplasia significantly and inversely correlated with patient age, from 91.5% for those aged 50 to 64 years to 83.7% for patients aged 65 years or older.

“Age-related variation in specificity could be due to the presence of lesions that were missed on colonoscopy (which are more prevalent among persons older than 70 years) or to age-related DNA methylation,” they suggest.

In an accompanying editorial, Douglas Robertson, from White River Junction Veterans Affairs in Vermont, USA, and Jason Dominitz, from the University of Washington in Seattle, USA, note that the DNA stool test completion was unsuccessful in more patients than the FIT (6.3 vs 0.3%).

Nevertheless, they say that the test is “clearly an improvement over its predecessors” and that the study results “will help to inform the current efforts of the U.S. Preventive Services Task Force to reevaluate screening tests.”

“Comparative-effectiveness studies are now needed to clarify the role of stool DNA testing with respect to programmatic screening with other test options”, Douglas Robertson and Jason Dominitz comment.

References

Imperiale T, Ransohoff D, Itzkowitz S, et al. Multitarget stool DNA testing  for colorectal cancer screening. New Engl J Med 2014; Advance online publication 19 March. DOI: 10.1056/NEJMoa1311194

Robertson D,  Dominitz J. Stool DNA and Colorectal-cancer screening. New Engl J Med 2014; Advance online publication 19 March. DOI: 10.1056/NEJMe1400092

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