Colorectal Cancer Screening

Colorectal cancer (CRC) is the 2nd-leading cause of cancer-related death in the United States. Almost all cases of CRC are adenocarcinoma and the majority of lesions come from the malignant transformation of an adenomatous polyp. As most CRCs are asymptomatic, screening is essential in detecting early disease. The test of choice is a colonoscopy, initiated by age 50 years and performed every 10 years (depending on findings) in an average-risk individual. For high-risk individuals, earlier and more frequent screening is recommended. Other stool-based strategies and visualization tests are also available for CRC screening.

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Overview

Colorectal cancer (CRC)

  • The majority of CRCs are adenocarcinomas.
  • Most CRCs arise from polyps (adenomatous or serrated).
  • Importance of screening for CRC:
    • 3rd-most common cancer (among both men and women)
    • 2nd-most common cause of death due to cancer in the United States
    • 94% of new cases of colorectal cancer occur in adults aged 45 years and older.
  • In 2016, about 25% of eligible adults had not been screened for CRC.

Risk factors

  • Age: 94% of new cases of CRC occur in adults aged 45 years and older.
  • Hereditary syndromes: 
    • Hereditary non-polyposis colorectal cancer (HNPCC) or Lynch syndrome
    • Familial adenomatous polyposis (FAP)
    • Peutz-Jeghers syndrome (PJS)
    • MUTYH-associated polyposis (MAP): a mutation in the base excision repair gene mutY homolog
    • Family history of CRC
  • Colon pathologies:
    • Inflammatory bowel disease (IBD)
    • Large adenomatous polyps or previous diagnosis of CRC
  • Other medical conditions:
    • Cystic fibrosis
    • Abdominopelvic radiation
    • Conditions with increased insulin or insulin-like growth factor (e.g., diabetes, acromegaly, obesity)
    • Streptococcus bovis bacteremia
    • Renal transplantation
  • Lifestyle and social factors:
    • Smoking and alcohol consumption (> 4 drinks/day)
    • Diet (increased fat, red and processed meat, low fiber)
    • Low socioeconomic status

Screening Rationale

Colorectal polyps

  • Abnormal tissue outgrowths arising from the colonic mucosa and extending into the lumen
  • Most common lesions from which CRC arises
  • Most common progression: small to large polyps → dysplasia → carcinoma
  • Development of CRC takes an average of 10 years.
  • 30% of the population has polyps by the age of 50.

Polyp of sigmoid colon revealed by colonoscopy: The polyp is pedunculated (with a short stalk).

Image: “Colon polyp” by Dr. F.C. Turner. License: CC BY 2.5

Benefits of screening

Colorectal cancer is generally a preventable cancer when proper screening is performed. Screening:

  • Prevents CRC by detection and removal of polyps
  • Identifies early-stage CRC, thereby improving prognosis and decreasing mortality rate

Strategies for Screening

Stool-based tests

  • High-sensitivity guaiac-based fecal occult blood test (HSgFOBT):
    • Identifies hemoglobin in stool
    • Positive test: Guaiac reagent turns paper blue (peroxidase reaction).
    • Restrictions:
      • Eliminate red meat (3 days before test).
      • Limit vitamin C to < 250 mg a day (3 days before test).
      • Nonsteroidal anti-inflammatory drug (NSAID) intake may affect the test.
    • 3 consecutive stool samples needed 
  • Fecal immunochemical test (FIT):
    • Measures hemoglobin in the stool
    • No medication or diet restrictions prior to the test
    • Only 1 sample needed
    • Should be submitted within 24 hours of collection
  • Stool DNA test:
    • Also called multitarget stool DNA testing (MT-sDNA)
    • Composite of tests:
      • Molecular assays testing for DNA (KRAS) mutations
      • Gene amplification technique testing for methylation biomarkers
      • FIT
    • Test available by prescription
    • No dietary or medication restrictions
    • A full stool sample is required.

Direct visualization tests

  • Colonoscopy:
    • Gold standard for detecting precancerous adenomas and CRC
    • Visualizes rectum, colon, and part of the terminal ileum
    • Both diagnostic and therapeutic (lesions can be biopsied and removed)
    • Requires medication adjustment (NSAIDs, aspirin, anticoagulant)
    • Requires bowel preparation
    • Sedation generally used
    • Procedure-related risks:
      • Perforation
      • Bleeding
      • Infection
  • Sigmoidoscopy:
    • Endoscope reaches up to the splenic flexure.
    • Allows visualization but only in the left colon (so right-sided lesions are missed)
    • Allows removal of lesions, but lesions > 1 cm usually done in subsequent colonoscopy
    • Requires medication adjustment (NSAIDs, aspirin, anticoagulant)
    • Performed in-office without sedation
    • Procedure-related risks:
      • Perforation (most common)
      • Bleeding
      • Infection
  • Computed tomography (CT) colonography:
    • Use of CT scanning to reconstruct bowel mucosa images in 2 and 3 dimensions
    • Needs bowel preparation, but sedation not required
    • The bowel is distended by introducing air or carbon dioxide via the rectum. 
    • Limitation(s): biopsy or lesion removal not possible
  • Colon capsule endoscopy (PillCam Colon 2):
    • The patient swallows a capsule with wireless video cameras. 
    • Images are taken as the capsule goes through the intestine.
    • Requires bowel preparation
    • Not indicated for screening, but to be used in case of incomplete colonoscopy
    • Limitation: biopsy or lesion removal not possible

Colorectal Cancer Screening for Average-Risk Individuals

For an average-risk individual, screening is initiated at 50 years of age (but can be offered at 45 years of age).

  • Characteristics of an average-risk individual:
    • No personal or family history of CRC or adenomatous polyp
    • No personal or family history of known genetic syndromes related to CRC
    • No inflammatory bowel disease
    • No prior abdominal radiation for childhood cancer
  • Options for screening:
    • Annual HSgFOBT
    • Annual FIT
    • sDNA-FIT test every 3 years
    • Flexible sigmoidoscopy every 5 years (limited to distal part of the colon)
    • Colonoscopy every 10 years
    • CT colonography every 5 years
  • A positive screening stool-based test, CT colonography, or sigmoidoscopy warrants a colonoscopy.
  • Screening is not recommended after age 75.

Colorectal Cancer Screening for High-Risk Individuals

  • Individuals with a family history of CRC (including advanced adenoma or advanced serrated lesion):
    • Colonoscopy at age 40 or 10 years earlier than the age of diagnosis of the 1st-degree relative (whichever comes first)
    • Repeat every 5 years.
    • If the patient declines colonoscopy, annual FIT testing is recommended.
  • Individuals with inflammatory bowel disease:
    • Begin 8 years post-diagnosis.
    • Colonoscopy with biopsies every 1–2 years
  • Individuals with classic familial adenomatous polyposis (FAP):
    • Associated with 100 or more adenomatous colorectal polyps
    • 100% risk of CRC
    • Screening:
      • Begin at 10–15 years of age.
      • Annual colonoscopy while awaiting colectomy
  • Individuals with hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome:
    • Begin at age 20–25 years or 2–5 years prior to the earliest age of CRC diagnosis in the family (whichever comes first).
    • Colonoscopy every 1–2 years
  • Individuals with Peutz-Jeghers Syndrome:
    • Begin screening at 8 years of age.
    • Subsequent screening interval depends if polyps are detected.
  • Individuals with juvenile polyposis:
    • Begin screening at 12 years of age (earlier if with symptoms).
    • If polyps are found, repeat colonoscopy yearly.
    • If no polyps are found, repeat colonoscopy every 1–3 years.

References

  1. Colorectal screening. United States Preventive Services Task Force. Retrieved December 9, 2020, from https://uspreventiveservicestaskforce.org/uspstf/draft-recommendation/colorectal-cancer-screening3#tab2
  2. Doubeni, C., Lamont, J., Elmore, J., Givens., J. (2020). Tests for screening for colorectal cancer. UpToDate. Retrieved December 9, 2020, from https://www.uptodate.com/contents/tests-for-screening-for-colorectal-cancer?search=colorectal%20screening&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1
  3. Macrae, F., Goldberg, R. & Seres, D., Savarese, D. (Eds.) (2020) Colorectal cancer: Epidemiology, risk factors and protective factors. UpToDate. Retrieved December 3, 2020, from https://www.uptodate.com/contents/colorectal-cancer-epidemiology-risk-factors-and-protective-factors?search=colorectal%20cancer%20epidemiology&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1
  4. Macrae, F., Lamont, T. & Grover, MD, S. (2020) Overview of colon polyps. UpToDate. Retrieved December 3, 2020, from https://www.uptodate.com/contents/overview-of-colon-polyps?search=overview%20of%20managememnt%20of%20colorectal%20cancer&source=search_result&selectedTitle=15~150&usage_type=default&display_rank=15
  5. Ursem C, & McQuaid K.R. (2021). Colorectal cancer. Papadakis M.A., & McPhee S.J., & Rabow M.W. (Eds.), Current Medical Diagnosis & Treatment 2021. McGraw-Hill.

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