, according to the large prospective BLUE-C study.
The multi-target assay by Exact Sciences Corporation, the makers of Cologuard, includes new biomarkers designed to increase specificity without decreasing sensitivity. It showed a sensitivity for CRC of almost 94%, with more than 43% sensitivity for advanced precancerous lesions and nearly 91% specificity for advanced neoplasia, according to the study results, which were published in The New England Journal of Medicine.
Indiana University School of Medicine
Dr. Thomas F. Imperiale
Adherence to CRC screening in the United States is well below the 80% national target, and the quest continues for noninvasive screening assays that might improve screening adherence, noted lead author Thomas F. Imperiale, MD, AGAF, a professor of medicine at Indiana University School of medicine in Indianapolis, and colleagues.
“The test’s manufacturer developed a new version of its existing Cologuard FIT/DNA test because it took to heart the feedback from primary care providers and gastroenterologists about the test’s low specificity,” Dr. Imperiale said in an interview. “The goal of the new test was to improve specificity without losing, and perhaps even gaining, some sensitivity — a goal that is not easily accomplished when you’re trying to improve on a sensitivity for colorectal cancer that was already 92.3% in the current version of Cologuard.”
Compared with the earlier version of Cologuard, he added, the new generation retained sensitivity for CRC and advanced precancerous lesions or polyps while improving specificity by 30% (90.6% vs 86.6%) for advanced neoplasia — a combination of CRC and advanced precancerous lesions, he said. “This with the caveat, however, that the two versions were not compared head-to-head in this new study,” Dr. Imperiale said.
The higher specificity for advanced lesions is expected to translate to a lower false positive rate. Lowering false positive rates is crucial because that reduces the need for costly, invasive, and unnecessary colonoscopies, said Aasma Shaukat, MD, MPH, AGAF, director of outcomes research in NYU Langone Health’s division of gastroenterology and hepatology in New York City.
New York University
Dr. Aasma Shaukat
“Many physicians felt there were too many false positives with the existing version, and that is anxiety-provoking in patients and providers,” said Dr. Shaukat, who was not involved in the study.
In her view, however, the test’s moderate improvements in detecting certain lesions does not make it demonstrably superior to its predecessor, and there is always the possibility of higher cost to consider.
While acknowledging that a higher sensitivity for all advanced precancerous lesions would have been welcome, Dr. Imperiale said the test detected 75% of the most worrisome of such lesions — “the ones containing high-grade dysplastic cells and suggesting near-term conversion to cancer. And its ability to detect other advanced lesions improved as the size of the lesions increased.”
