Table 2.

Advantages and disadvantages of recommended and emerging CRC screening modalities

Method	Advantages	Disadvantages
Stool-based strategies recommended by the USPSTF
High-sensitivity guaiac fecal occult blood test (HSgFOBT)	• Mortality benefit in prospective longitudinal studies [1, 4, 9] • With perfect adherence, can achieve the most life-years gained compared to other screening tests [73] • Highly accessible and can be performed in non-clinical settings • Less invasive than direct visualization techniques • Low cost	• Abnormal test requires follow-up colonoscopy [3••] • Annual testing required [4••] • Dietary and medication restrictions prior to testing [4••] • Requires multiple stool samples each year [4••] • Should not be performed in presence of upper or lower gastrointestinal bleeding [8]
Fecal immunochemical test (FIT)	• Mortality benefit in retrospective studies [3••] • Increased participation compared to other modalities (colonoscopy, FOBT, sigmoidoscopy) [74] • Highly accessible and can be performed in non-clinical settings • Less invasive than direct visualization techniques • Low cost • No dietary restriction or bowel preparation required [3••] • Requires only one stool sample [3••] • Can be performed in setting of upper gastrointestinal bleeding [10] • Similar rates of CRC detection compared to flexible sigmoidoscopy	• Abnormal test requires follow-up colonoscopy [3••] • Annual testing required [3••] • Less sensitive for detecting CRC and adenomas than other modalities (CT colonography, capsule endoscopy, stool DNA) [66]
Multi-target stool DNA (mt-sDNA) test	• High participation (Exact Sciences patient navigation) [17] • Can be performed in non-clinical settings • Less invasive than direct visualization techniques • No dietary restriction or bowel preparation required [4, 18] • Requires only one stool sample [4••] • More sensitive that FIT alone [3••] • Testing can be performed every 3 years	• No data to support an incidence or mortality benefit [3••] • Abnormal test requires follow-up colonoscopy [3••] • Lower specificity compared to FIT resulting in more false positive results [3, 4] • Lower positive predictive value and detection rate for advanced adenomas compared to CT colonography [18] • High cost compared to other stool-based strategies [11]
Direct visualization techniques recommended by the USPSTF
Computed tomography (CT) colonography	• Lower risk of complications compared to colonoscopy [3••] • Less invasive compared to colonoscopy [3••] • Lower cost compared to colonoscopy [69] • Does not require sedation [3••] • Can visualize the entire colon [4••] • Less frequent testing interval than stool-based modalities [23] • Relatively safe for individuals with medical comorbidities that preclude colonoscopy [3, 24] • Can allow for same day endoscopic evaluation if indicated [18] • High positive predictive value [18]	• No data to support an incidence or mortality benefit [4••] • Abnormal test requires follow-up colonoscopy [3••] • Requires dietary modification and bowel preparation [3••] • Less precise compared to other modalities [3••] • Requires exposure to radiation [3••]
Flexible sigmoidoscopy	• Mortality benefit when combined with annual FIT screening [4••] • Lower risk of complications compared to colonoscopy [4, 30] • Lower cost compared to colonoscopy [30] • Does not require sedation or oral bowel preparation [4, 30] • Allows for direct visualization of rectum, sigmoid colon and descending colon • Less frequent testing interval than FIT, HSgFOBT [4••] • Can be performed by broader range of clinicians than colonoscopy	• Studies show reduction in distal CRC incidence but no reduction in proximal CRC incidence [30] • Abnormal test requires follow-up colonoscopy [3••] • Requires per rectal bowel preparation (enema) [3••] • Does not examine entire colon [3, 4] • Low patient participation compared to stool- based screening strategies [30]
Colonoscopy	• Mortality benefit in retrospective studies [32, 33] • Allows for direct visualization of entire colon • Potential for least frequent testing interval • Allows for resection or biopsies of concerning lesions	• Invasive procedure typically performed under conscious sedation or anesthesia • Higher rate of complications compared to other direct visualization techniques [3••] • Requires bowel preparation and diet modification [4••] • Low accessibility in some populations and regions • Low patient participation [34] • Has a high degree of operator variability [3••] • Higher cost than other screening options [11]
Emerging technologies (Not currently USPSTF recommended)
Colon capsule endoscopy	• Less invasive than direct visualization techniques [3••] • Does not require sedation [3••] • Can be performed in non-clinical settings [3••] • Lower risk of complications compared to colonoscopy [39]	• Not currently recommended by the USPSTF for CRC screening for average-risk individuals due to limited evidence [3••] • No data to support an incidence or mortality benefit • Abnormal result requires follow-up colonoscopy [3••] • Dietary restrictions and colon preparation may be required [4••] • Possibility of capsule retention in small bowel [3••] • Unclear ideal screening interval [3••] • Low accessibility in some populations and regions • Higher cost than colonoscopy [40] • Interpretation requires provider trained in reading capsule endoscopy [3••]
Blood-based/liquid biopsy	• Less invasive than direct visualization techniques [45] • No dietary restriction or bowel preparation required • Potential for broad availability and multiple cancer testing [39] • Will likely have high adherence compared to traditional methods [42••]	• Not currently recommended by the USPSTF for CRC screening for average-risk individuals due to limited evidence [3••] • No data to support an incidence or mortality benefit • Abnormal result requires follow-up colonoscopy [3••] • Only one test is currently FDA-approved (Epi proColon; Epigenomics AG, 2016) [41, 44] • Unclear cost and ideal testing interval
Stool-based microbiome tests and urine-based tests	• Less invasive than direct visualization techniques [49] • Can be performed in non-clinical settings [49] • Limited evidence showed greater sensitivity for adenomatous polyps compared to FIT (urine-based test) [50]	• Not currently recommended by the USPSTF for CRC screening for average-risk individuals due to limited evidence [3••] • No data to support an incidence or mortality benefit • Abnormal result requires follow-up colonoscopy [3••] • Low sensitivity and specificity compared to other techniques [48] • High cost due to genomic/metagenomic sequencing [47] • Unclear ideal testing interval • Does not distinguish by polyp size or stage of CRC [52]

Abbreviations: USPSTF United States Preventive Services Task Force, CRC colorectal cancer, FDA Food and Drug Administration