Building a Better FIT Test for Colon Cancer Screening

By Megan Brooks

July 20, 2021

NEW YORK (Reuters Health) - An antibody-based multitarget fecal immunochemical test (mtFIT) for colorectal cancer (CRC) screening is more accurate in detecting advanced neoplasia compared with the standard FIT test, without compromising specificity, report Dutch researchers.

"Early detection of colorectal cancer can save many lives and the mtFIT is cost-effective approach to substantially improve upon the widely used FIT by detecting more advanced adenomas," Dr. Mieke de Wit, with Netherlands Cancer Institute, Amsterdam, said in email to Reuters Health.

The standard FIT test detects hemoglobin in stool and is proven effective for reducing CRC incidence and death. The sensitivity of FIT in one round of screening is high for CRC, but the sensitivity for relevant precursor lesions, advanced adenomas and advanced serrated polyps is much lower.

There is a need for a noninvasive screening test that has higher sensitivity for precursor lesions without increasing false-positive test results, the study team explains in a paper in Annals of Internal Medicine.

The mtFIT test combines three biomarkers - hemoglobin calprotectin and serpin family F member.

In a diagnostic test accuracy study using bio-banked residual FIT kit buffer from 1,284 individuals, mtFIT had significantly higher sensitivity than FIT for advanced neoplasia (.i.e., CRC and advanced precursor lesions: 42.9% vs. 37.3%, P=0.025) with equal specificity of 96.6%.

The improvement with mtFIT over FIT was specifically seen in the advanced adenomas, for which sensitivity increased by 35% (37.8% vs. 28.1%, P=0.006), while sensitivity for CRC did not change.

"Health technology modeling showed that when performed biennially and compared to traditional biennial FIT, mtFIT would reduce CRC incidence and mortality by 12% and 8%, respectively, and could be cost-effective compared to FIT," Dr. de Wit told Reuters Health.

The greater sensitivity of mtFIT "may prove critical to improving FIT's performance as a cancer prevention test," Dr. Jason Dominitz, with the National Gastroenterology and Hepatology Program, Veterans Health Administration, Washington, DC, says in an editorial.

"This study is important because the challenge of building a better screening test was approached from the perspective of an organized, population-based screening program, and it shows the potential of relatively inexpensive enhancements to the widely used FIT to improve sensitivity without sacrificing specificity," Dr. Dominitz writes.

"Ultimately, this study offers promise of incremental but important improvements in the effectiveness of population-based CRC screening through novel biomarker measurement using an existing screening platform," Dr. Dominitz adds.

Dr. de Wit told Reuters Health the research team is preparing a prospective trial with 13,000 participants in the context of the Dutch national CRC screening program in which they will compare mtFIT head-to-head to the current FIT test. "Here we hope to collect final evidence that the mtFIT test will result in the detection of more advanced adenomas and CRC. In that case, replacing FIT by mtFIT would be a very realistic scenario for improving population based CRC screening," Dr. de Wit said.

"Personalized screening that takes into account these biomarkers as well as demographic characteristics, exposures (for example, tobacco), and genetic information may eventually be adopted," Dr. Dominitz notes in his editorial.

"However, in the meantime, let's encourage ongoing efforts to optimize screening as we endeavor to continue our progress in reducing CRC incidence and death," he writes.

Funding for the study was provided by Stand Up to Cancer/Dutch Cancer Society, Dutch Digestive Foundation, and HealthHolland.

SOURCE: https://bit.ly/36NltFi Annals of Internal Medicine, online July 19, 2021.

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