Current state and future direction of screening tool for colorectal cancer

Table 1 Characteristics of colorectal cancer screening tests currently in use in the United States

Screening test		Interval	Evidence	Advantages	Disadvantages	Other considerations
Stool-based screening tests
FIT with high sensitivity123		Every year	Improved performance compared with high-sensitivity gFOBT Mortality reduction: indirect evidence from RCTs of guaiac-based stool tests	Can be performed at home Requires only a single specimen No diet or medication restrictions Does not require bowel preparation or anesthesia Inexpensive compared with structural examinations and mt-sDNA	High nonadherence to yearly testing (especially without reminder systems) Less effective for advanced adenoma detection Few accessible tests have published peer-reviewed performance data	Varies in test performance due to brand and version Follow-up colonoscopy for positive test may charge extra costs
gFOBT with high sensitivity12 (HSgFOBT)		Every year	Good RCT evidence for incidence and mortality reduction[112-116] Varies in test performance characteristics by version of the test	Inexpensive compared with structural examinations and mt-sDNA Can be done at home Does not require bowel preparation or anesthesia	High nonadherence to yearly testing (especially without reminder system) Less effective for advanced adenoma detection Difficulty in determining test performance among the many FDA-cleared tests Requires multiple samples Requires dietary and medication restriction Higher false-positive rate than FIT leads to more colonoscopies	Follow-up colonoscopy for positive test may charge extra costs
mt-sDNA1		Every 3 yr	Mortality reduction: indirect evidence from RCTs of guaiac-based stool tests Improved sensitivity for cancer and AA and poorer specificity compared with FIT	Can be done at home Does not require bowel preparation or anesthesia	More expensive than other stool-based tests Higher false-positive rate than FIT	Follow-up colonoscopy for positive test may charge extra costs A new test with limited data on screening outcomes. Uncertainty in management of positive results followed by a negative colonoscopy
FIT-DNA23		Every 1 or 3 yr	Test characteristic studies	Improved sensitivity compared with FIT per single screening test Does not require bowel preparation or anesthesia Can be done at home	Higher false-positive rate than FIT	Uncertainty in management of positive results followed by a negative colonoscopy
Direct visualization screening tests
Colonoscopy123	Every 10 yr		Non-RCT evidence of incidence and mortality reduction Prospective cohort study with mortality end point	Requires less frequent screening Screening, diagnosis, treatment and prevention through polypectomy can be done at the same-session. Gross visualization of the entire colon	Pain and discomfort Lower tolerability and compliance than FS[117] Possibility of bowel perforation / bleeding and cardiopulmonary complications from anesthesia Requires full bowel cleansing Performance varies upon adequacy of bowel preparation, the cecal intubation rate, withdrawal time, and adenoma detection rate Lower sensitivity for neoplasia in the proximal than the distal colon	Polypectomy and anesthesia may charge extra costs Most expensive test, but currently reimbursable with insurance Requires day-off (if sedation is used)
CTC123	Every 5 yr		Test characteristic studies Extrapolation from RCTs of sigmoidoscopy demonstrating mortality reduction	Rapid, non-invasive imaging method Well-tolerated by patients Does not require anesthesia Better tolerability and acceptance than colonoscopy and FS[118]	Exposure to low-dose radiation Requires full bowel cleansing A second bowel cleansing will be required before Follow-up colonoscopy for positive test	Follow-up colonoscopy for positive test may charge extra costs Insufficient evidence about the benefit-burden balance of additional tests on incidental extracolonic findings Relatively expensive and may not be covered by insurance
FS123	Every 5 yr		RCTs with mortality end points:	Does not require anesthesia Requires more limited bowel cleansing Better acceptance than colonoscopy[117]	Pain and discomfort Does not examine the proximal Colon Requires enema prior to procedure Abnormal findings require second colonoscopy	Follow-up colonoscopy for positive test may charge extra costs Concerns about lack of quality standards, limited availability, failure to achieve a complete examination
FS with FIT2	FS every 10 yr plus FIT every year		RCT with mortality end point (subgroup analysis)	More benefits than when combined with FIT or compared with other strategies It may be an potentially option for patients who want endoscopy screening but do not want colonoscopy		Test declined in the US

¹The American Cancer Society Guidelines recommend.

²US Preventive Services Task Force Guidelines recommend.

³The U.S. Multi-Society Task Force Guidelines recommend [Tier 1: Colonoscopy every 10 yr, annual fecal immunochemical test; Tier 2: CT colonography every 5 yr, FIT-fecal DNA every 3 yr, flexible sigmoidoscopy every 10 years (or every 5 yr); Tier 3: Capsule colonoscopy every 5 yr]. CRC: Colorectal cancer; CTC: Computed tomographic colonography; FDA: US Food and Drug Administration; FIT: Fecal immunochemical test; FS: Flexible sigmoidoscopy; gFOBT: Guaiac-based fecal occult blood test; mtsDNA: Multitarget stool DNA; RCT: Randomized controlled trial.