COLON CANCER SCREENING - AVERAGE RISK


















American College of Gastroenterology 2021
Whom to screen
  • Age 45 - 49 years: suggest screening average-risk individuals (conditional recommendation, low evidence)
  • Age 50 - 75 years: recommend screening average-risk individuals (strong recommendation, moderate evidence)
  • Age > 75 years: decision to continue screening should be individualized (conditional recommendation, low evidence)
Screening methods
  • Colonoscopy every 10 years or annual FIT are preferred
  • For patients unwilling to undergo colonoscopy or annual FIT, consider the following:
    • Flexible sigmoidoscopy every 5 - 10 years
    • Fecal DNA test every 3 years
    • CT colonography every 5 years
    • Colon capsule every 5 years
  • mSEPT9 DNA testing (Epi proColon┬«) is not recommended [18]
U.S. Preventive Services Task Force 2020
Whom to screen
  • Age 45 - 49 years: screen everyone (Grade B: high certainty that net benefit is moderate)
  • Age 50 - 75 years: screen everyone (Grade A: high certainty that net benefit is substantial)
  • Age 76 - 85 years: screening should be individualized and based on overall health and prior screening results
  • Age > 85 years: screening not recommended
Screening methods (no single method is preferred over another)
  • Colonoscopy every 10 years
  • CT colonography every 5 years
  • Fecal DNA-FIT testing every 3 years or every year
  • FIT every year
  • Flexible sigmoidoscopy every 5 years
  • Flexible sigmoidoscopy every 10 years + FIT every year
  • High-sensitivity guaiac-based fecal occult blood test every year (Hemoccult SENSA)
American College of Physicians 2019
Whom to screen
  • Screen everyone aged 50 - 75. Do not screen before 50 or after 75. Do not screen those with a life expectancy of ≤ 10 years.
Screening methods (no single method is preferred over another)
  • Colonoscopy every 10 years
  • FIT every 2 years
  • High-sensitivity (gFOBT) every 2 years
  • Flexible sigmoidoscopy every 10 years with FIT every 2 years [12]
British Medical Journal 2019
Whom to screen
  • Recommendations are intended for the U.K. population
  • Estimate the 15-year colorectal cancer risk using the QCancer® 15-year colorectal risk calculator
  • For individuals aged 50 - 79 years and estimated risk < 3%, do not screen
  • For individuals aged 50 - 79 years and estimated risk ≥ 3%, screen with one of the methods below
  • Do not screen those with a life expectancy of < 15 years
Screening methods (no single method is preferred over another)
  • FIT every 1 or 2 years
  • A single colonoscopy
  • A single sigmoidoscopy [17]
American Cancer Society 2018
Whom to screen
  • Screen everyone beginning at age 45. The ACS makes no recommendation on an age to stop screening.
Screening methods (no single method is preferred over another)
  • Colonoscopy every 10 years
  • CT colonography every 5 years
  • Flexible sigmoidoscopy every 5 years
  • Double contrast barium enema every 5 years
  • Guaiac-based fecal occult blood test every year (use high-sensitivity test like Hemoccult SENSA)
  • FIT test annually
  • Fecal DNA-FIT every 3 years [16]
U.S. Multi-Society Task Force on Colorectal Cancer 2017
Whom to screen
  • Start screening African Americans at age 45. Screen everyone else at age 50.
  • Persons who are up to date with screening and have negative prior screening tests, particularly colonoscopy, consider stopping screening at age 75 or when life expectancy is less than 10 years
  • Persons without prior screening should be considered for screening up to age 85, depending on consideration of their age and comorbidities.
Screening methods
  • Colonoscopy every 10 years (Tier 1, preferred)
  • FIT every year (Tier 1, preferred)
  • CT colonography every 5 years (Tier 2)
  • Fecal DNA-FIT test every 3 years (Tier 2)
  • Flexible sigmoidoscopy every 5 - 10 years (Tier 2)
  • Capsule colonoscopy every 5 years (Tier 3) [15]
Canadian Task Force on Preventive Health Care 2016
Whom to screen
  • Screen everyone aged 50 - 74. Do not screen before 50 or after 75.
Screening methods:
  • Flexible sigmoidoscopy every 10 years + FIT or gFOBT every two years [13]



  • Advanced adenoma defined as adenoma with any of the following: ≥ 10 mm in size, tubulovillous or villous histology, high-grade dysplasia
Colonoscopy
Description
  • Procedure where an endoscope is inserted through the anus and advanced all the way to the terminal ileum
  • Endoscope allows visualization of the entire colon and a portion of the terminal ileum
  • Advantages: allows visualization of the entire colon; considered the "gold standard" for colon cancer screening/detection; allows for biopsy of lesions and removal of polyps; if normal, screening interval is 10 years
  • Disadvantages: invasive procedure that requires sedation; bowel prep is required that may be uncomfortable; serious adverse events (e.g. bleeding, perforation) occur in about 0.28% of procedures [4]
Accuracy
  • Colonoscopy is considered the reference standard
  • It is estimated that the colorectal cancer miss rate for colonoscopy is as high as 6%. The miss rate for adenomas > 1 cm is 12 - 17%. [4]
Recommendations
  • ACP - screen everyone every 10 years starting at age 50
  • ACS - screen everyone every 10 years starting at age 45
  • BMJ - screen individuals 50 - 79 years old with 15-year estimated risk ≥ 3% one time
  • USMSTF - start screening African Americans at age 45. Screen everyone else at age 50. Screen every 10 years.
  • USPSTF - screen everyone every 10 years starting at age 50
Cost
  • $911 - $6946, depending on insurer and location
  • Cost is higher if biopsies are performed
Flexible sigmoidoscopy (flex sig)
Description
  • Procedure where an endoscope is inserted through the anus and advanced into the sigmoid colon. The standard sigmoidoscope is 60 cm long.
  • Approximately two-thirds of colorectal cancers and adenomas are located in the rectum and sigmoid colon [7]
  • Advantages: performed in office without sedation; prep only requires 2 fleet enemas although oral prep may be better; allows for biopsy and polypectomy
  • Disadvantages: only allows visualization of the sigmoid and descending colon; patient discomfort; perforation and bleeding are rare but may occur [6]
Accuracy
  • No well-done studies have compared flexible sigmoidoscopy to colonoscopy in average-risk populations
Recommendations
  • ACP
    • Flex sig + FIT - starting at age 50, perform flex sig every 10 years and FIT every 2 years
  • ACS - starting at age 45, screen every 5 years
  • BMJ - screen individuals 50 - 79 years old with 15-year estimated risk ≥ 3% one time
  • CTFPHC - starting at age 50, perform flex sig every 10 years and FIT or gFOBT every 2 years
  • USMSTF - start screening African Americans at age 45. Screen everyone else at age 50. Screen every 5 - 10 years. (Tier 2)
  • USPSTF
    • Flex sig alone - starting at age 50, screen every 5 years
    • Flex sig + FIT - starting at age 50, perform flex sig every 10 years and FIT annually
Cost
  • $500 - $3000 depending on insurer and location
  • Cost is higher if biopsies are performed
CT colonography
Description
  • Specialized CT scan of the abdomen that creates 2D and 3D images of the colon for polyp and neoplasm detection
  • Patient must undergo bowel prep beforehand. A small amount of contrast may be mixed with the prep so that residual fluid and stool is "tagged." This helps distinguish the residua from soft tissue masses.
  • During the scan, a rectal tube is inserted so that the colon can be insufflated with CO2 or room air
  • Patients with polyps ≥ 6 mm are referred for colonoscopy [6]
  • Advantages: no sedation is required; procedure takes about 10 minutes with no recovery time; colon perforation is rare; in studies, significant extracolonic findings are found in 4.5% of patients
  • Disadvantages: bowel prep is recommended; colonoscopy may be necessary depending on findings; patient receives small amount of radiation; extracolonic findings may lead to unnecessary testing [6]
Accuracy
  • Sensitivity (colorectal cancer): 96%
  • Sensitivity (adenomas ≥ 10 mm): 85 - 93%
  • Specificity (adenomas ≥ 10 mm): 97%
  • Sensitivity (adenomas 6 - 9 mm): 70 - 86%
  • Specificity (adenomas 6 - 9 mm): 86 - 93% [6]
Recommendations
  • ACS - starting at age 45, screen everyone every 5 years
  • USMSTF - start screening African Americans at age 45. Screen everyone else at age 50. Screen every 5 years. (Tier 2)
  • USPSTF - starting at age 50, screen everyone every 5 years
Cost
  • $300 - $1500 depending on the insurer and location
  • Reimbursement for screening varies
Fecal immunochemical test (FIT)
Description
  • Like gFOBT, FIT is performed on a stool sample collected by the patient
  • FIT testing detects human globin, a component of human hemoglobin. FIT differs from gFOBT in that it directly detects blood in the stool where gFOBT relies on the peroxidase activity of hemoglobin.
  • FIT testing is also more specific for lower GI bleeding because globulin is degraded by digestive enzymes in the upper GI tract
  • Diet, medications, and supplements are not supposed to interfere with FIT testing, although some studies have found that FIT testing has a lower positive predictive value (PPV) in patients taking aspirin or anticoagulants [PMID 30689972]. Another study found that taking an aspirin 2 days before FIT testing did not increase the sensitivity of the test. [PMID 31063574]
  • Examples of currently available FIT tests include Hemoccult ICT, OC-Light, Hemosure, QuickVue iFOB, and Clearview. Some tests use cards and some tests use bottles. The optimal number of samples to test has not been determined but varies from one to three. The US Multi-Society Task Force on colorectal cancer recommends testing one sample.
  • Most tests give only qualitative result (positive or negative) while a few tests give qualitative and quantitative results (i-Chroma iFOBT, OC-Micro, OC-Sensor) [5,6,14]
  • Advantages: performed at home; no procedure; inexpensive; no diet or medication restrictions
  • Disadvantages: positive result requires colonoscopy; more frequent testing; does not detect polyps
Accuracy
  • Hemoccult ICT
    • Sensitivity (colorectal cancer): 82%
    • Specificity (colorectal cancer): 97%
    • Sensitivity (advanced adenoma): 30%
    • Specificity (advanced adenoma): 97% [9]
    • NOTE: In this study (n=5356), the reference standard was flex sig or colonoscopy, and three stool samples were tested
  • OC FIT-CHEK
    • Sensitivity (colorectal cancer): 74%
    • Sensitivity (advanced adenoma): 24%
    • Specificity (negative colonoscopy): 96% [10]
    • NOTE: In this study (n=9989), only one stool sample was tested
Recommendations
  • ACP
    • FIT alone - screen every 2 years starting at age 50
    • Flex sig + FIT - starting at age 50, perform flex sig every 10 years and FIT every 2 years
  • ACS
    • FIT alone - screen annually starting at age 45
    • Fecal DNA-FIT - screen every 3 years starting at age 45
  • BMJ - screen individuals 50 - 79 years old with 15-year estimated risk ≥ 3% every 1 or 2 years
  • CTFPHC - starting at age 50, perform flex sig every 10 years and FIT or gFOBT every 2 years
  • USMSTF
    • FIT alone - start screening African Americans at age 45. Screen everyone else at age 50. Screen annually. (Tier 1, preferred)
    • Fecal DNA-FIT - screen every 3 years starting at age 50 (Tier 2)
  • USPSTF
    • FIT alone - screen annually starting at age 50
    • FIT + Flex Sig - starting at age 50, perform flex sig every 10 years and FIT annually
    • Fecal DNA-FIT - screen every 3 years starting at age 50
Cost
  • $10 - $20
Guaiac-based fecal occult blood test (gFOBT)
Description
  • Guaiac-based fecal occult blood tests detect blood in the stool through the pseudoperoxidase activity of hemoglobin
  • Patients typically collect 1 stool sample on 3 different days at home. The samples are developed in a doctor's office or lab.
  • NSAIDs should be avoided for 7 days before and during the collection period
  • Vitamin C in excess of 250 mg/day should be avoided for 3 days before and during the collection period (may cause false-negative)
  • Red meats should be avoided for 3 days before and during the collection period
  • Specimens should be developed within 14 days of collection
  • Hemoccult SENSA is more sensitive than Hemoccult II [5,6]
  • Advantages: performed at home; no procedure; inexpensive
  • Disadvantages: diet and drug restrictions; positive result requires colonoscopy; more frequent testing; does not detect polyps; low sensitivity
Accuracy
  • Hemoccult II
    • Sensitivity (colorectal cancer): 13%
    • Sensitivity (advanced adenoma): 11%
    • Specificity (combined): 95% [8]
  • Hemoccult SENSA
    • Sensitivity (colorectal cancer): 64%
    • Specificity (colorectal cancer): 90%
    • Sensitivity (advanced adenoma): 41%
    • Specificity (advanced adenoma): 91% [9]
    • NOTE: In this study (n=5799), the reference standard was flex sig or colonoscopy
Recommendations
  • ACP - screen every 2 years starting at age 50 (use high-sensitivity test like Hemoccult SENSA)>/li>
  • ACS - screen annually starting at age 45 (use high-sensitivity test like Hemoccult SENSA)
  • CTFPHC - starting at age 50, perform flex sig every 10 years and FIT or gFOBT every 2 years
  • USPSTF - screen annually starting at age 50 (use high-sensitivity test like Hemoccult SENSA)
Cost
  • $6 - $20
Fecal DNA test (Cologuard®)
Description
  • Fecal DNA tests are performed on a single sample of stool that is collected by the patient at home. A FIT test is also performed with the fecal DNA test. If the FIT test is positive and the DNA test is negative, the results come back as positive.
  • Colorectal cancers and adenomas continually shed cells into the stool. These cells contain certain types of genetic mutations that are common in many cancerous and precancerous tumors. Fecal DNA tests are able to detect these mutations in cells present in the stool sample.
  • The test is not 100% sensitive in that not all cancers or precancerous lesions carry the genetic mutations that are detected. [5,6,10]
  • Advantages: performed at home; no procedure; no diet or medication restrictions
  • Disadvantages: positive result requires colonoscopy; expensive; does not detect all cancers; manufacturer does not report FIT results and DNA results separately; optimal screening interval has not been determined; unclear how to handle a positive test that is followed by a negative colonoscopy
Accuracy
  • Cologuard without FIT
    • Sensitivity (colorectal cancer): 92%
    • Sensitivity (advanced adenoma): 42%
    • Specificity (negative colonoscopy): 90% [10]
Recommendations
  • ACS - screen every 3 years starting at age 45
  • USMSTF - start screening African Americans at age 45. Screen everyone else at age 50. Perform test every 3 years. (Tier 2)
  • USPSTF - screen every 3 years starting at age 50
Cost
  • $500 - $600
Double-contrast barium enema (air-contrast barium enema)
Description
  • Procedure where a tube is inserted into the rectum and barium is infused. The patient's position is adjusted under fluoroscopy so that the barium coats the entire lining of the colon. After removing some barium, the colon is then insufflated with air. Air and barium serve as the "double-contrast," and radiographic images are obtained.
  • Colon prep before the procedure is required. The procedure typically lasts 20 - 40 minutes. [6]
  • Advantages: no sedation is required; no recovery time
  • Disadvantages: bowel prep is required; colonoscopy may be necessary depending on findings; exam can be uncomfortable; test accuracy highly dependent on examiner's experience
Accuracy
  • Sensitivity (colorectal cancer): 85 - 97%
  • Sensitivity (adenomas > 7 mm): 73% (based on 1 study, n=56) [6]
Recommendations
  • ACS - screen everyone every 5 years starting at age 45
Cost
  • $350 - $1000 depending on insurance and location
mSEPT9 DNA testing (Epi proColon®)
Description
  • mSEPT9 DNA testing is performed on a blood sample
  • The test detects methylated SEPT9 DNA, which in high quantities, is a marker for colorectal cancer
  • The test is marketed under the name Epi proColon® [11]
  • Advantages: blood test; no procedure
  • Disadvantages: low sensitivity; positive result requires colonoscopy; does not detect polyps
Accuracy
  • Sensitivity (colorectal cancer): 48%
  • Sensitivity (advanced adenoma): 11%
  • Specificity (colorectal cancer): 92% [11]
Recommendations
  • No organization currently recommends this test
Cost
  • ∼ $91