Patients with adenomas larger than 5 millimeters or other abnormal results are referred for colonoscopy, optimally on the same day in order to alleviate the necessity of a second bowel preparation. Studies have shown that the performance of CTC is similar to colonoscopy for the detection of invasive cancer and advanced adenomas, but has lower sensitivity for smaller adenomas.241 Potential harms include cumulative radiation exposure from regular examinations, and unnecessary tests and/or treatment due to incidental benign findings outside the colorectum. There is less evidence on the benefits and harms of this test compared to others because it is relatively new and remains uncommon.224 This may be because it is not covered by Medicare and commercial insurance coverage is variable; in 2019, 37 states mandated that commercial plans cover this test.242 Stool tests Most cancerous tumors and some large adenomas bleed intermittently into the intestine. This blood, which may not be visible, can be detected in stool with special tests. Modeling studies suggest that annual screening with high-sensitivity stool tests and timely follow-up of abnormal results will result in a reduction in mortality similar to that achieved by colonoscopy over a lifetime of screening.243 Except for the multitargeted stool DNA test, which is recommended every 3 years, stool tests should be repeated annually. However, adherence to yearly testing and timely follow-up with a colonoscopy after a positive test remains a challenge, especially in lowresource settings where stool tests are more common.244-247 Guaiac-based fecal occult blood test (gFOBT) These tests use a chemical reaction to detect blood in the stool. Bleeding from cancers or adenomas may be sporadic or undetectable, so accurate results require annual testing of samples from 3 consecutive bowel movements. Patients are typically instructed to avoid nonsteroidal anti-inflammatory drugs and red meat for 3 days prior to the test because they can lead to a positive test result when no cancer is present (false positive); gFOBT detects blood from any source, including meat in the diet. Vitamin C and large amounts of citrus juices should also be avoided because they can lead to a negative test result when cancer is present (false negative). Only high-sensitivity gFOBT are recommended for CRC screening. 22 Colorectal Cancer Facts & Figures 2020-2022 Data from a large clinical trial indicated that the regular use of FOBT reduced the risk of CRC death by 32% after 30 years of follow-up.248 FOBT has also been shown to decrease CRC incidence by 20% by detecting large precancerous adenomas.249 Fecal immunochemical test (FIT) The FIT (also sometimes referred to as the immunochemical FOBT, or iFOBT) uses antibodies against hemoglobin to specifically detect human blood in the stool and is about twice as likely as most gFOBT products to detect both advanced adenomas and cancer.250, 251 Many individuals prefer FIT over gFOBT because of its convenience, lack of dietary restrictions, and collection of fewer stool samples.252 Multitargeted stool DNA (Cologuard®) This test is referred to as “multitargeted” because it not only detects blood in the stool, but also multiple genetic mutations in the DNA of cells that are shed into the stool by large adenomas and CRC. Cologuard® has been shown to detect cancer and precancerous lesions more often than FIT, but also results in more false-positive tests, which can lead to unnecessary colonoscopies.253 However, because it is a relatively new test, data are still accumulating on performance characteristics in community settings. Although it is recognized as an acceptable screening option by the American Cancer Society and the US Preventive Services Task Force224 and is covered by Medicare, some private insurance companies may not cover this test. Patient navigation services, which include phone calls and reminder letters in multiple languages to support test completion, are embedded in the cost of the test, although the services do not extend to colonoscopy follow-up of abnormal results.254 Non-recommended tests for colorectal cancer screening There are several tests