. 2022 May 3;19(8):521–531. doi: 10.1038/s41575-022-00612-y

Table 1.

Summary of non-invasive CRC screening options

Test	Evidence for efficacy	Test details and special considerations	Recommended frequency
*Stool based*
FIT	Sensitivity for CRC 79% and specificity 94%¹³; reduces CRC incidence by 22%⁹⁸; sensitivity increases with repeated tests over time^128,129; low sensitivity for advanced adenomas¹⁴	Positive test needs confirmation diagnostic colonoscopy; in the USA, annual testing required; can be performed in patient’s home; no dietary or medication restrictions; conducive to programmatic screening	Annual in the USA^15–17; see below for intervals elsewhere
FIT-DNA (mtsDNA) Cologuard	Sensitivity for CRC 92% and specificity 87%³⁰ ; superior to FIT for detection of CRC and advanced precancerous lesions^130,131; sensitivity for advanced polyps 42%³⁰ ; higher false-positive rate than FIT^33,34	Positive test needs confirmation diagnostic colonoscopy; manufacturer recommends repeat testing every 3 years based on modelling studies only; single stool specimen can be collected at home; no cathartic bowel preparation or anaesthesia required; built-in patient navigation enhances adherence; 3- year interval based on modelling studies; there is limited empirical data upon which to base a recommendation; false positives can result in over-testing and harms; high cost compared to FIT³¹	Every 3 years²³
*Blood based*
Septin 9 (mSEPT9) Epi pro Colon	Sensitivity for CRC 48.2–68% and specificity 80–91.5%^71,132; direct comparison shows non-inferior sensitivity but lower specificity than one-time FIT for CRC⁷² ; direct comparison shows lower sensitivity for CRC and adenomas vs mtsDNA testing⁷³	Positive test needs confirmation diagnostic colonoscopy; screening interval not established; blood plasma assay; cannot be done with home phlebotomy; concern for false negatives	Not recommended by US guidelines or any outside the USA
*Imaging based*
Colon capsule	Sensitivity for polyps ≥6 mm 88% and specificity 82%⁶¹; sessile serrated polyps and hyperplastic polyps accounted for 26–37% of false-negative findings on capsule analysis⁶¹	Positive test needs confirmation diagnostic colonoscopy; repeat screening interval unknown but 5 years recommended by experts; more extensive bowel preparation than traditional colonoscopy with the potential requirement of additional pro-kinetic agents on exam day; large capsule can be difficult to swallow; delayed transit can cause incomplete exam (if exceeds battery time)	5 years¹⁶
CT colonography	Sensitivity for adenomas ≥6 mm 73–98% and specificity 89–91%; pooled sensitivity of adenomas ≥10 mm 67–94%, specificity96–98%¹³³; low detection rate for sessile and flat polyps^134,135	Positive test needs confirmation diagnostic colonoscopy; incidental extracolonic findings lead to downstream testing and treatment; lifetime risk of cumulative radiation exposure unknown	Every 5 years

CRC, colorectal cancer; FIT, faecal immunochemical testing; mSEPT9, methylated septin 9; mtsDNA, multitarget stool DNA.