Description

• The rectum is the distal portion of the colon bound by the end of the sigmoid colon and the anal verge. A tumor whose distal margin is typically 12 to 15 cm from the anal verge measured by rigid proctoscope should be classified as a rectal cancer.
• Distal rectum is defined as area distal to the middle rectal valve, usually 8 to 9 cm from the anal verge. Defining distal rectum is important in determination of eligibility for sphincter preservation surgery.
• Colon and rectal cancers are often grouped together but are two distinct clinical entities that differ in their presentation, staging, and management.

Epidemiology

Incidence
97,220 new cases of colon cancer and 43,030 new cases of rectal cancer in 2018; and 50,630 deaths from colon and rectal cancer combined are expected in the United States in 2018 (1). Rectal carcinomas account for 28% of these cases (2).

Prevalence

• The lifetime risk for developing colorectal cancer (CRC) in the United States is about 1 in 21 (4.8%).
• Incidence and death rates have been declining due to improved screening, prevention, and treatment.

Etiology and Pathophysiology

• Progression from the first abnormal cells to the appearance of CRC usually occurs over 10 to 15 years; a disease characteristic that contributes to the effectiveness of prevention
• High-risk polyp findings include multiple polyps, villous polyps, and larger polyps.
• Hyperplastic polyps are less likely to evolve into CRC.
• Multiple genetic and environmental factors have been linked to the development of CRC.

Genetics

• <10% of CRC cases are linked to an inherited gene.
  • APC, a tumor suppressor gene, is altered in familial adenomatous polyposis (FAP).
  • Genes encoding DNA mismatch repair (MMR) enzymes are implicated in hereditary nonpolyposis colon cancer (HNPCC): MLH1, MSH2, MSH6, PMS1, PMS2, and others.
  • STK11, a tumor suppressor gene, is altered in Peutz-Jeghers syndrome.
• Sporadic cases of CRC have been linked to oncogenes: Kras, c-Myc, c-Src, HER2/neu, and others.

Risk Factors

• Age: >90% of people diagnosed with CRC are >50 years of age.
• Personal history of colorectal polyps
  • Risks increase with multiple polyps, villous polyps, and larger polyps.
• Personal history of cancer
  • 8-fold increase in risk of developing CRC
  • Rectal cancer has higher incidence of local recurrence than proximal cancers (20–30% vs. 2–4%).
• History of inflammatory bowel disease (IBD)
  • 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.
• 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 those who have a history of CRC or polyps in
    • Any first-degree relative <60 years of age
    • ≥2 first-degree relatives, regardless of age
• Inherited syndromes
  • Hereditary nonpolyposis CRCs (formerly Lynch syndrome)
    • Often develops at younger age (Average age at diagnosis of CRC is 44 years.)
    • Lifetime risk of CRC is 52–69%.
    • Accounts for ~2% of all CRCs
  • FAP
    • Affected individuals develop hundreds to thousands of polyps in colon and rectum.
    • CRC usually present by age 40 years.
    • Accounts for <1% of CRCs
  • Peutz-Jeghers syndrome
    • Individuals may have hyperpigmented mucocutaneous lesions (mouth, hands, feet) and large polyps in GI tract.
    • 81–93% risk for CRC and increased risk for other cancers
• Race and ethnicity
  • African Americans have the highest CRC incidence and mortality rates in the United States. It is unclear whether this is biologic or due to lower rates of access to screening.
  • Colonoscopy is underutilized, particularly in minorities.
  • Several different gene mutations have been identified among Ashkenazi Jews.
• Lifestyle factors that increase risk
  • Diets high in red and processed meats
  • Low levels of physical activity
  • Alcohol consumption
  • Smoking

General Prevention

• Optimal screening method for colon cancer is unclear. Stool-based testing such as gFOBT and fecal immunochemical test (FIT) or FIT-DNA tests are less invasive, but endoscopic testing such as flexible sigmoidoscopy or colonoscopy offers ability to provide intervention if polyp discovered.
• Compared to no endoscopic screening, screening colonoscopy has been associated with 67% reduction in the risk of death from any CRC.
• Lifestyle factors that may reduce risk
  • Low-fat, high-fiber diet (rich in fruits and vegetables)
  • Supplementation with vitamin D, calcium, folate, and fiber may lower CRC risk; more research is needed to understand how diet affects risks of CRC.
  ALERT
  The U.S. Preventive Services Task Force (USPSTF) strongly recommends screening men and women between the ages of 50 and 75 years for CRC.
• American Cancer Society recommendations for screening may include the following (3):
  • Colonoscopy every 10 years
  • Flexible sigmoidoscopy every 5 years
  • FIT annually
  • Fecal occult blood testing annually
  • CT colonography every 5 years (colonoscopy completed if positive)*
  • Double-contrast barium enema every 5 years*
  • Stool DNA (sDNA) test every 3 years*
  • *The USPSTF does not recommend barium enema as a screening test and concludes the evidence is insufficient to assess the benefits and harms of CT colonography and sDNA testing as screening modalities for CRC.
• Screening in high-risk groups: See “Colon Cancer.”