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 2.5Benefits 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
Colon cancer found on colonoscopy confirmed via biopsy
Image: “Primary tumor” by Second Department of Surgery, Wakayama Medical University, School of Medicine, 811-1 Kimiidera, Wakayama 641-8510, Japan. License: CC BY 2.0
Computed tomographic colonography (CTC) and colonoscopy:
Image: “LST” by Division of Screening Technology and Development, Research Center for Cancer Prevention and Screening, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. License: CC BY 3.0
A: Colonoscopy view of the lesion
B: Lesion became apparent by indigo-carmine spraying.
C: CTC showing laterally spreading lesion
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.
References
- Colorectal screening. United States Preventive Services Task Force. Retrieved December 9, 2020, from https://uspreventiveservicestaskforce.org/uspstf/draft-recommendation/colorectal-cancer-screening3#tab2
- 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
- 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
- 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
- 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.
