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Developing a better fecal immunochemical test (FIT) for colon cancer screening
The fecal immunochemical test (FIT) is a widely used colorectal cancer (CRC) screening test that uses a specific antibody to detect hemoglobin in the stool – an indication of the presence of blood which can be sign of pre-cancer. FIT can be sent to a person by mail and completed at home, and does not require any type of bowel preparation to be done beforehand. In the instance that blood is detected in the stool, the individual will be referred by their doctor to have either:
• A colonoscopy, which uses a thin, flexible tube with a light and a camera at the end inserted into the rectum to examine the lining of the entire colon (large intestine)
• A flexible sigmoidoscopy, which uses a soft, flexible tube with a light and a camera at the end inserted into the rectum to examine the lining of the rectum and lower part of the colon (sigmoid colon).
The FIT is an appropriate test for the initial round of CRC screening because of its high diagnostic accuracy and higher participation rate compared to colonoscopy. However, a major pitfall of FIT as a CRC screening method is that the detection rate and diagnostic capacity for advanced CRC adenomas and advanced serrated polyps is lower than that associated with colonoscopy2.
Due to the need for a better non-invasive screening test that has a higher sensitivity (the ability of the test to correctly identify individuals with pre-cancer) for more advanced CRC adenomas without increasing overall false positives, a recent study conducted in the Netherlands aimed to evaluate the effectiveness of a multitarget FIT (mtFIT) which targets several different biomarkers in addition to the standard hemoglobin FIT.
The mtFIT examines stool for the presence of three different biomarkers – hemoglobin, calprotectin, and serpin family F member. The investigators found that mtFIT had significantly higher sensitivity than standard FIT for detecting advanced adenomas and an equivalent specificity (the ability of the test to correctly identify individuals without the disease) of 96.6%. For the detection of advanced adenomas, the mtFIT sensitivity increased by 35% compared to standard FIT (37.8% vs 28.1% respectively), while the sensitivity for detecting CRC remained the same.
The findings are important, as they show the benefit of relatively inexpensive improvements through the addition of specific biomarkers to the population-based FIT to increase its sensitivity.
The research team will be preparing a large, prospective trial with 13,000 participants within the Dutch national CRC screening program in which mtFIT will be compared directly to the standard FIT, providing the final evidence on the sensitivity of the mtFIT compared to the standard FIT.
 Quintero E, et al. Colonoscopy versus fecal immunochemical testing in colorectal-cancer screening. N Engl J Med 2012;366:697–706