• Clinical science

Colorectal cancer

Summary

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in both women and men in 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: ∼ 130,000 new cases per year
    • Third most common cancer in women and men
  • Age: continuous increase in incidence after the age of 50
  • Mortality: third leading cause of cancer-related deaths in the US overall


References:[1][2][3][4][5][6]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

Predisposing factors

Protective factors

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

References:[1][3][7][8][9]

Clinical features

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

Iron deficiency anemia in men > 50 years and postmenopausal women should be considered a sign of colorectal cancer until proven otherwise!

References:[10][11][12][13][9]

Stages

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

AJCC staging (simplified) TNM stage Corresponding Dukes classification stage Description
I Up to T2, N0, M0 A Invasion of submucosa
II Up to T4, N0, M0 B Invasion of muscularis propria but no lymph node involvement
III Any T, N1/N2, M0 C Invasion of subserosa or beyond (e.g., pericolic and perirectal fat) with no involvement of other organs but with lymph node involvement
IV Any T, any N, M1 D Invasion of visceral peritoneum or adjacent organs (distant metastasis)

References:[11][12]

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

  • Determine the extent of local and distant disease
    • Endorectal ultrasound: determine depth of tumor infiltration
    • CT of abdomen, pelvis, and chest
    • CXR
  • Tumor marker: carcinoembryonic antigen (CEA) serum levels prior to initiating treatment

References:[1][1][12][14]

Pathology

95% of all colorectal cancers are adenocarcinomas!

References:[15][16][17]

Differential diagnoses

Small bowel neoplasms

References:[18]

The differential diagnoses listed here are not exhaustive.

Treatment

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

Colon cancer

  • Curative approach: any primary tumor with or without regional spread; resectable metastases in the liver and/or lung
    • Treatment involves surgical resection and adjuvant chemotherapy.
  • Palliative approach: distant metastases beyond the liver and/or lung or if the patient is not a surgical candidate due to poor general health

Surgical management

Systemic therapy

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

Rectal cancer

Surgical management

  • Transanal excision
    • Procedure: minimally invasive excision of small superficial tumors
    • Indications: early, localized disease (stage I)
  • Low anterior resection (LAR)
    • 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
    • Indications: locally advanced disease (Stage III–IV)
  • The completeness of the TME has a strong impact on the prognosis!
  • Abdominoperineal resection (APR)
    • Procedure: resection of the rectum, sigmoid, and anus with TME and permanent colostomy
    • Indications: last resort if the distal margin to the rectum cancer is < 2–5 cm to the anus
  • Palliative procedures include transanal excision or diverting colostomy to facilitate defecation.

Systemic therapy

  • Neoadjuvant radiochemotherapy: locally advanced disease (stages II–III) typically followed by surgery and postoperative chemotherapy
  • Adjuvant chemotherapy after surgical resection depending on the pathologic work-up
  • Palliative chemotherapy: inoperable, metastatic disease (stage IV)

Follow-up

  • Monitor patients for 5 years following the completion of treatment
    • Patient history, physical examination, CEA level: every 3–6 months for 3 years, then every 6 months for 2 years
      • Elevated CEA warrants further evaluation to determine site of recurrence or metastasis with CT of the chest and abdomen, PET, and/or colonoscopy.
    • Colonoscopy: after surgical resection, then 1 year after surgery, then every 3–5 years

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

References:[1][19][13][20][21][22][23][24][25][26][27][28][9][29][30]

Prognosis

  • Overall 5-year survival rate: 65%
  • Survival rate according to disease stage
    • Stage I: 95%
    • Stage II: ∼ 80% [31]
    • Stage III: 60%
    • Stage IV: 5–10%

References:[11][13][32]

Prevention

Screening for colorectal cancer

Screening for colorectal cancer and adenomatous polyps is performed in asymptomatic men and women ≥ 50 years of age.

  • Low-risk individuals: several options
    • 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
    • Sigmoidoscopy every 5 years and FOBT every 3 years
    • Annual fecal immunochemical testing (FIT)
    • CT colonography every 5 years
  • High-risk individuals
    • Complete colonoscopy 10 years earlier than the index patient's age at diagnosis or no later than 40 years of age
    • In case of genetic predisposition: individual screening (see FAP and HNPCC for details)
Surveillance following polypectomy
Histology of removed polyp Recommended interval until next control colonoscopy
10 years
  • Low risk adenoma: 1–2 tubular polyps < 10 mm in size and without intraepithelial neoplasia (IEN)
5–10 years
  • High risk adenoma
    • 3–10 tubular polyps
    • 1 polyp ≥ 10 mm
    • 1 villous or tubulovillous polyp
    • 1 tubular polyp with high-grade dysplasia
3 years
< 3 years; depends on the case (i.e., family history)



References:[13][33][34][35][36]