Description

• Colon and rectal cancers (CRC) are often grouped together but are two distinct clinical entities that differ in their prognosis, presentation, staging, and management.
• CRC is the third leading cause of cancer-related deaths in men, the fourth leading cause in women, and the second leading cause when numbers for men and women are combined in the United States.

Epidemiology

Etiology and Pathophysiology

• Progression from the first abnormal cells to colon cancer occurs over 10 to 15 years.
• High-risk polyps: multiple polyps, villous, sessile serrated, or dysplastic polyps and larger polyps; hyperplastic polyps are less likely to evolve into CRC.

Risk Factors

• Age: The incidence of colon cancer increases between 40 and 50 years old. ~87% of those with new CRC diagnosis will be >50 years old; younger patients are more likely to have advanced disease at the time of diagnosis.
• Personal history of colorectal polyps: The risk increases with multiple polyps, villous polyps, larger polyps (>1 cm), and presence of dysplasia.
• Personal history of cancer
  • 30% increase in risk of developing metachronous (new primary tumors unrelated to the patients’ previous cancers) colon cancer
  • 2–4% incidence of local recurrence with colon cancer, 3–5% incidence of synchronous colon cancer
  • History of radiation therapy to the abdomen/pelvis
• Personal history of inflammatory bowel disease (IBD)
  • The risk of CRC begins ~8 years after the onset. Prevalence of CRC in ulcerative colitis and Crohn disease is ~3%, with a cumulative risk of CRC of 2% at 10 years, 8% at 20 years, and 18% at 30 years.
  • Ulcerative colitis with pancolitis up to 10-fold risk of CRC, 8 to 10 years after initial diagnosis
• Anal human papillomavirus
• Family history of CRC
  • Having a single first-degree relative with a history of CRC increases risk ~1.7-fold.
  • Risk is more than double for with a history of CRC or polyps in:
    • Any first-degree relative <50 years of age; ≥2 first-degree relatives, regardless of age; one first-degree and one second-degree relative
• Inherited syndromes
  • HNPCC
    • Often develops at younger age (~48 years)
    • With right-sided lesions
  • FAP: Affected individuals develop hundreds to thousands of polyps in colon and rectum, typically presenting during childhood with CRC present by age 40 years in untreated patients; most have prophylactic colectomies
  • Peutz-Jeghers syndrome
    • Individuals may have hyperpigmented mucocutaneous lesions (mouth, hands, feet) and large polyps in GI tract discovered as an adolescent.
    • 81–93% risk for cancers including CRC, cancers of pancreas, breast, cervix, testes, and lung
• Race and ethnicity: African Americans have the highest CRC incidence and mortality rates in the United States.
• Lifestyle factors: smoking, obesity, sedentary activity, insulin resistance, low intake of calcium, whole-grain, and/or fiber-rich foods, high consumption of red and processed meat, excessive alcohol

General Prevention

• Lifestyle factors and medications that may reduce risk:
  • Regular physical activity, diet high in fiber 30 g/day), and fruits and vegetables
  • There is conflicting evidence on folic acid, calcium, vitamin D, magnesium, NSAIDs, fish oil, and statins.
  ALERT
  
  The U.S. Preventive Services Task Force (USPSTF) states all adult ≥45 years should be offered screening regardless of the presence of the risk factors (recommendation for 45 to 49 years old with Grade B and 50 to 75 years old with Grade A) (1). For ages 76 to 85 years old, screening should be based on overall health status and life expectancy and should involve shared decision-making.
• Screening methods (2):
  • Visualization-based tests:
    • Colonoscopy every 10 years (primary screening modality)
    • Flexible sigmoidoscopy every 10 years with a high-sensitivity fecal immunochemical test (FIT) annually
    • Flexible sigmoidoscopy every 5 to 10 years
    • Capsule colonoscopy every 5 years (considered 3rd tier for those unwilling)
  • Stool-based tests
    • FIT
    • Multitarget stool DNA test (Cologuard) every 3 years
    • High-sensitivity guaiac fecal occult blood test (gFOBT) annually
  • Imaging-based tests:
    • CT colonography every 5 years
    • For patients who have a positive noncolonoscopy-based CRC test (stool-based, flexible sigmoidoscopy, CT colonography), a colonoscopy is recommended.
• Colonoscopy:
  • People who have a first-degree relative or two second-degree relatives with CRC or advanced polyps before age 60 years should begin colonoscopy at age 40 or ≤10 years than the youngest age of the affected relative, whichever is earlier. Repeat every 5 years.
  • Patients with IBD should start surveillance colonoscopies every 1 to 2 years and 8 to 10 years after diagnosis.
  • Genetic testing may be appropriate for individuals with a strong family history of CRC or polyps:
    • Family members of a person with HNPCC should start colonoscopy starting at age 20 to 25 years or 2 to 5 years prior to the youngest age of the affected relative at the time of cancer diagnosis, whichever occurs first and repeated every 1 to 2 years.
    • Individuals with suspected FAP should have colonoscopy every 1 to 3 years, beginning at age 10 to 14 years.
• Frequency of follow-up of polyps:
  • 2 to 6 months: following piecemeal (unable to remove with single loop) removal of a large polyp ≥20 mm
  • 1 year:
    • Known FAP or at risk based on family history
    • >10 adenomatous polyps
  • 1 to 2 years: IBD (Crohn disease or ulcerative colitis)
  • 3 years:
    • 5 to 10 tubular adenomas <10 mm
    • 5 to 10 sessile serrated polyps
    • Tubular adenoma ≥10 mm
    • Sessile serrated polyp ≥10 mm
    • Adenoma with villous or tubulovillous histology and/or high-grade dysplasia
    • Sessile serrated polyp with dysplasia
    • Traditional serrated adenoma
  • 3 to 5 years:
    • 3 to 4 sessile serrated polyp <10 mm without dysplasia
    • 3 to 4 adenomas <10 mm
    • Hyperplastic polyps ≥10 mm
    • History of colon cancer s/p surgery if initial 1-year follow-up is normal
  • 5 to 10 years: 1 to 2 sessile serrated polyp <10 mm without dysplasia
  • 7 to 10 years: 1 to 2 adenomas <10 mm
  • 10 years:
    • Normal screening colonoscopy with no polyps
    • ≤20 hyperplastic polyps <10 mm
• Some international organizations recommend screening for anal cancer via rectal swab at:
  • 35 years old for those with HIV especially men who have sex with men and transgender women.
  • 45 years old for those without HIV especially men who have sex with men and transgender women.

Commonly Associated Conditions

• HNPCC, Gardner, Crail (Turcot), FAP, Peutz-Jeghers, juvenile polyposis syndromes, MAP, and cystic fibrosis (CF)
• IBDs including Crohn disease and particularly ulcerative colitis with pancolitis