• Clinical science

Colorectal cancer

Summary

Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer the United States. Risk factors include a positive family history, hereditary syndromes, diet, and a number of conditions, such as inflammatory bowel disease. Most colorectal cancers are adenocarcinomas (95%). Clinical signs are often nonspecific and may include a change in bowel habits, rectal bleeding, and weight loss. Iron deficiency anemia in men > 50 years and postmenopausal women should be considered a warning sign for CRC. Since the introduction of screening with colonoscopy or sigmoidoscopy and fecal occult blood testing, early stage carcinomas have become easier to diagnose in asymptomatic patients. Complete colonoscopy with histopathologic analysis confirms the diagnosis. Staging of the cancer is necessary to evaluate the extent of the disease and determine the appropriate treatment. Curative surgical resection of colorectal cancers and metastases is the preferred method of treatment. Colon cancers are resected via hemicolectomy, while rectal cancers are preferably resected via low anterior resection with total mesorectal excision. Resection is complemented by adjuvant chemotherapy for colon cancer, and neoadjuvant and adjuvant chemoradiation for rectal cancer. Regular follow-ups are recommended after surgical resection.

Epidemiology

  • Incidence [1][2]
    • Fourth most common cancer in the US overall
    • Accounts for ∼ 8% of all new cancer cases in the US
    • Peak incidence: between 65 and 74 years of age
  • Prevalence: ∼ 0.4%
  • Mortality: second leading cause of cancer-related deaths in the US overall

Epidemiological data refers to the US, unless otherwise specified.

Etiology

Risk factors [3]

Protective factors [3]

  • Long-term use of aspirin and other NSAIDs
  • Physical activity
  • Diet rich in fiber and vegetables and lower in meat

Clinical features

Overview

  • Often times asymptomatic, particularly during the early stages

Constitutional symptoms [6]

Symptoms of right-sided carcinomas [6][7]

Iron deficiency anemia in men > 50 years and postmenopausal women should raise suspicion for colorectal cancer.

Symptoms of left-sided carcinomas [6][7]

  • Definition
  • Symptoms
    • Changes in bowel habits (size, consistency, frequency)
    • Blood-streaked stools
    • Colicky abdominal pain (due to obstruction)
    • Mostly infiltrating mass

Symptoms of rectal carcinomas [6][7]

Colorectal cancer must be ruled out in a patient presenting with rectal bleeding, even if the patient has a history of hemorrhoids.

Symptoms of advanced disease

Symptoms of metastatic disease [8]

Stages

The stages of colorectal cancer are based on the TNM staging system by the American Joint Committee for Cancer (AJCC).

Stages of colorectal cancer
AJCC staging (simplified) TNM stage Corresponding Dukes classification stage Description
I
  • Up to T2, N0, M0
  • A
II
  • Up to T4, N0, M0
  • B
  • Tumor invasion
    • T1: submucosa
    • T2: muscularis propria
    • T3: subserosa
    • T4a: visceral peritoneum
    • T4b: other organs
  • N0: no lymph node involvement
  • M0: no distant metastases
III
  • Any T, N1/N2, M0
  • C
IV
  • Any T, any N, M1
  • D
  • Tumor invasion: any structure
  • Lymph node involvement: any number
  • Distant metastases
    • M1a: affecting only one organ
    • M1b: affecting more than one organ or peritoneal carcinomatosis

Diagnostics

Work-up of colorectal cancer is indicated in symptomatic patients and asymptomatic patients with abnormalities detected during routine screening.

Initial work-up

In up to 5% of cases, multiple adenocarcinomas are present. A complete colonoscopy is necessary to rule out additional tumors.

Staging and further tests

  • Determination of disease extent
  • Treatment monitoring: via carcinoembryonic antigen (CEA)
    • Can not be used for screening
    • Assess serum levels prior to initiating treatment
    • Monitor CEA levels during the course of treatment and the follow-up period to evaluate treatment response and recurrence

Pathology

Histopathology

95% of all colorectal cancers are adenocarcinomas.

Molecular pathology [10][11]

Differential diagnoses

Small bowel neoplasms

The differential diagnoses listed here are not exhaustive.

Treatment of colon cancer

Approach [13]

Treatment primarily depends on the location of the tumor and the TNM stage.

  • Curative approach
  • Palliative approach
    • Distant metastases beyond the liver and/or lung
    • Patient is not a surgical candidate due to poor general health.
    • Treatment involves palliative chemotherapy and palliative surgery.

Surgical management

Colectomy

Regional lymph node dissection

Resection of metastases in liver and/or lung

Palliative surgery

  • Enteral stenting
  • Bypass (e.g., ileocolonic anastomosis)
  • Resection
  • Colostomy

Systemic therapy

Chemotherapy

Biologicals

Radiation therapy

  • Not a standard modality for treatment of colon cancer due to adverse effects on the small intestine, leading to enteritis and strictures
  • Used in palliative cases to treat bone and brain metastases

Radiation therapy is not a standard modality in the treatment of colon cancers.

Treatment of rectal cancer

Surgical management [14]

Transanal excision

  • Indication: early, localized disease (stage I)
  • Procedure: minimally invasive excision of small superficial tumors

Low anterior resection (LAR)

  • Indication: locally advanced disease (stage II–III)
  • Procedure: sphincter-preserving resection of the rectum and sigmoid
    • Total mesorectal excision (TME): en bloc excision of the mesorectum, regional lymph nodes, and vasculature
    • Resection 5 cm beyond the proximal margin of the tumor
    • Resection > 2 cm beyond the distal margin of well-differentiated tumors or > 5 cm beyond the distal margin of poorly differentiated tumors
    • Reconstruction (e.g., side-to-side anastomosis) and optional diverting ostomy
  • Limitations: A minimum distal margin to the tumor is required for reconstruction and preservation of anorectal function.

The completeness of the TME has a strong impact on the prognosis.

Abdominoperineal resection (APR)

  • Indication: last resort if the distal margin to the rectum cancer is < 2–5 cm to the anus
  • Procedure: resection of the rectum, sigmoid, and anus with TME and permanent colostomy

Systemic therapy

Prognosis

Prevention

Screening for colorectal cancer

Screening for colorectal cancer and adenomatous polyps is performed in asymptomatic men and women ≥ 45 years of age.

Low-risk individuals

  • Complete colonoscopy (gold standard): Repeat every 10 years if no polyps or carcinomas are detected.
  • Annual fecal occult blood test (FOBT): screening for occult bleeding, which may indicate colorectal cancer
  • Flexible sigmoidoscopy every 5 years and FOBT every 3 years
  • Annual fecal immunochemical testing (FIT)
  • FIT-DNA test every 3 years [15]
  • CT colonography every 5 years

High-risk individuals

  • Definition
    • History of adenomatous polyps or CRC
    • Positive family history: first-degree relative with CRC
    • Hereditary syndromes associated with increased risk of CRC (e.g., FAP, HNPCC)
  • Procedure
    • Complete colonoscopy 10 years earlier than the index patient's age at diagnosis or no later than 40 years of age
    • Individual screening protocols for individuals with inflammatory bowel disease or genetic predisposition (see “FAP” and “HNPCC)

Surveillance [16]

Surveillance following polypectomy
Histology Recommended interval until next control colonoscopy

Hyperplastic polyp

  • 10 years

Low-risk adenoma

  • 5–10 years

High-risk adenoma

  • 3 years

> 10 adenomas

Follow-up [17]

Every patient needs to be monitored for 5 years following the completion of treatment.

  • Patient history, physical examination CEA level
    • Every 3–6 months for 2 years
    • Every 6 months for additional 3 years
  • Chest/abdominal CT: every 6–12 months for 5 years
  • Colonoscopy
    • 1 year after surgical resection
    • 4 years after surgical resection
    • 9 years after surgical resection

85% of recurrences occur within the first three years following treatment.