Next-Generation Noninvasive Colorectal Cancer Screening.

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Noninvasive tests for colorectal cancer (CRC) screening in average-risk individuals continue to evolve, with the premise of increasing screening participation among eligible individuals. In addition to fecal immunochemical testing (FIT), which has become the noninvasive standard for which to improve sensitivity for detecting CRC and specificity for detecting the absence of CRC, new US Food and Drug Administration-approved tests include the detection of DNA in a next-generation multitarget stool DNA test, the detection of RNA in a multitarget stool RNA test, and blood tests that detect cell-free DNA for genomic alterations, fragmentations, and aberrant methylation, all of which have undergone large clinical trials for effectiveness. Each of these new tests improves upon the CRC sensitivity of FIT but not its specificity. Test sensitivity for CRC detection in persons <50 years of age is comparable to that in persons >50 years. Fecal tests with direct sampling of stool have improved sensitivity for advanced adenomas compared to FIT, but advanced adenoma sensitivity is regressed in blood tests compared to FIT. With about a third of the screening-eligible population not actively screened in the United States, the expansion of the screening-eligible population to include those >45 years of age, the disparity in some populations with lower-than-average screening rates, and the limited colonoscopy screening opportunities due to choice, schedule, availability, or pandemic interruption, these noninvasive tests may fill the gap and rectify CRC screening shortcomings and barriers that colonoscopy alone cannot fill.

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Critical considerations of fecal occult blood tests for colorectal cancer
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  • Robert Jc Steele + 1 more

1University of Dundee, Nethergate, Dundee, DD1 4HN, Scotland, UK *Author for correspondence: r.j.c.steele@dundee.ac.uk The most commonly used strategy in colo­ rectal cancer (CRC) screening pro grams involves the use of stool tests to detect occult blood, and guaiac fecal occult blood tests (gFOBTs) are, to date, the only fecal tests shown to reduce CRC mortality in population­based randomized trials [1]. However, gFOBTs also carry disadvantages. A major concern is that interval cancers account for around 50% of cancers detected in gFOBT screened populations [2] and recent data show that gFOBTs are less sensitive in women than in men, and in both rectal and right­sided cancers when compared with left­sided disease [2,3]. In addition, the test is associated with a high false­positive rate with no neoplasia detected in around half of colonoscopies performed following a positive gFOBT [2,3]. This may be, in part, explained by the fact that gFOBTs are not specific for human hemoglobin (Hb) and are subject to possible dietary interference from, for example, red meat and high­peroxidase fruits and vegetables. As a result, it has been common practice to instruct participants to adhere to dietary restrictions ahead of sample collection, although this may act as a barrier to screening and affect participation rates [4]. However, data from a meta­analysis did not support dietary restrictions with gFOBTs, leading to recommendations that restrictions are abandoned to improve adherence rates [5]. Fecal immunochemical tests (FITs) are now available and are increasingly being used in screening programs. Unlike gFOBTs, FITs are specific for the detection of human Hb, eliminating any potential for dietary interference, and are also more specific than gFOBT for lower gastrointestinal bleeding. In addition, modern FITs generally allow a more convenient method of sample collection, and are associated with better participation rates [6]. Another major advantage of FIT is that automated versions not only eliminate interobserver variability, but also the quantitative nature of these tests allow provision of a measured fecal Hb concentration. Screening program “...the adoption of fecal immunochemical tests in colorectal cancer screening programs has potential to address participation, appropriate positivity rates and the problem of false‐negative results.” EDITORIAL

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Is this the end of colonoscopy screening for colorectal cancer? An Asia-Pacific perspective.
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