Colorectal Cancer Screening

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.

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 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)
  • Flexible sigmoidoscopy every 10 years plus annual FIT
  • Colonoscopy every 10 years
  • CT colonography every 5 years
• A positive screening stool-based test, CT colonography, or sigmoidoscopy warrants a colonoscopy.
• Selective screening for adults aged 76–85 years, which may be based on:
  • Patient preferences
  • Prior screening results
  • Overall health status/comorbidities

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.