Colorectal cancer

Last updated: June 14, 2023

Summarytoggle arrow icon

Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer 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 (95%) are adenocarcinomas. Clinical signs are often nonspecific and may include a change in bowel habits, lower GI bleeding, and weight loss. These features as well as iron deficiency anemia in men older than 50 years of age and postmenopausal women are red flags for CRC. Since the introduction of screening with direct visualization or stool-based 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 disease and determine the appropriate management. Curative surgical resection of colorectal cancers and metastases is preferred when feasible. The type and extent of resection depend on the stage of the cancer. In addition, for cancer stages ≥ II, chemotherapy is required for colon cancer and chemotherapy and/or radiation therapy for rectal cancer. Surveillance following CRC treatment is essential to identify and manage recurrence and/or metastases. As the incidence of CRC is high, screening for CRC is recommended for all individuals, starting at 45–50 years of age (earlier in high-risk individuals).

Epidemiologytoggle arrow icon

  • Incidence [1][2]
    • Excluding skin cancers, colorectal cancer is the 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: third leading cause of cancer-related deaths in the US overall

Epidemiological data refers to the US, unless otherwise specified.

Etiologytoggle arrow icon

Colorectal carcinogenesis pathways (molecular pathology)

Risk factors for colorectal cancer [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 featurestoggle arrow icon

Colorectal cancer can be asymptomatic, particularly during the early stages.

Constitutional symptoms [7]

Right-sided colon carcinomas [7][8]

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

Left-sided colon carcinomas [7][8]

  • Definition: large bowel malignancies arising from the splenic flexure, descending colon, sigmoid colon, or the rectosigmoid junction
  • Clinical features
    • Changes in bowel habits (size, consistency, frequency)
    • Blood-streaked stools
    • Colicky abdominal pain (due to obstruction)

Bowel obstruction occurs earlier in left-sided colon carcinomas because the distal colon has a smaller lumen than the proximal colon and contains solid fecal matter.

Rectal carcinomas [7][8]

Cancers located ≤ 15 cm proximal to the anal verge are considered rectal carcinomas; cancers above this point are considered colon cancers.

Consider colorectal cancer in every patient with rectal bleeding, even if there is a history of hemorrhoids or diverticular disease.

Metastatic disease [10]

CRC can metastasize through hematogenous, lymphatic, transperitoneal, and contiguous routes. Symptomatic metastases may be the first manifestation of CRC.

Typically, cancers of the colon and upper rectum initially metastasize to the liver via the portal vein, and cancers of the lower rectum initially metastasize to the lung via the inferior vena cava.

Red flags for colorectal cancer [13][14][15]

The sensitivity and specificity of symptoms of colorectal cancer are limited. The following features have the strongest association with CRC, especially in patients with risk factors for colorectal cancer, and should always prompt further investigation.

Diagnosticstoggle arrow icon

All patients with suspected CRC should undergo a complete colonoscopy with biopsy of suspicious lesions. Once the diagnosis is confirmed, additional tests to stage the cancer are required to guide management.

Initial workup [9][16]

Digital rectal examination

Flexible sigmoidoscopy with or without anoscopy [13]

Complete colonoscopy

Colonoscopy is the gold standard test for CRC as it allows for direct visualization and biopsy of polyps and suspicious lesions. [17]

A complete colonoscopy is imperative in all patients with suspected/confirmed CRC as multiple adenocarcinomas (synchronous tumors) are present in up to 5% of cases. [20]

Double-contrast barium enema (uncommonly performed)

  • Indication: an alternative to CT colonography in patients who decline/cannot undergo a complete colonoscopy at presentation
  • Findings
    • Endoluminal filling defect typically with irregular margins
    • Apple core lesion (napkin ring sign): sharply defined circumferential narrowing of the bowel caused by a stenosing CRC [16][21][22]
  • Important considerations

Preoperative staging

Laboratory studies [16]

CEA is a prognostic marker and should not be used to screen for colorectal cancer.

Stagestoggle arrow icon

Once the diagnosis is confirmed, CRC should be staged to determine management. The American Joint Committee for Cancer (AJCC) TNM classification is currently the standard staging system used in clinical practice. The Dukes classification is a simplified approach to staging that is of academic interest but is not used to guide management.

Colorectal cancer staging
AJCC staging 8th edition (simplified) [31] TNM stage Corresponding Dukes classification stage Description
  • A
  • Up to T2, N0, M0
  • Up to T4, N0, M0
  • B
  • Any T, N1/N2, M0
  • C
  • Any T, any N, M1
  • D

Differential diagnosestoggle arrow icon

Differential diagnoses based on clinical presentation

Small bowel neoplasms

The differential diagnoses listed here are not exhaustive.

Treatmenttoggle arrow icon

General principles [9][16]

Surgery for colorectal cancer [9][16]

Curative surgery

Palliative surgery

Consider in patients with nonresectable distant metastases to prevent or treat complications of colorectal cancer.

Systemic therapy [9][16][34]

Systemic therapy is indicated in most patients with colon or rectal cancer. See “Treatment of colon cancer by stage” and “Treatment of rectal cancer by stage” for details. [34][35]

Radiation therapy

  • Rectal cancer: standard treatment modality in most stages of rectal cancer [9]
  • Colon cancer

Treatment of colon cancertoggle arrow icon

Principles of colon cancer treatment [16]

Treatment of colon cancer by stage
AJCC stage Treatment approach
Stage I
Stage II
Stage III
Stage IV

The treatment of colon cancer is mainly surgical, supplemented with chemotherapy. Radiation therapy is not a standard therapeutic modality for colon cancers.

Surgery for colon cancer [16][38][39]

Typical surgeries for colon cancer [38][39][41]
Type of resection Description Indication
Hemicolectomy Right hemicolectomy
Extended right hemicolectomy
Left hemicolectomy
Sigmoid colectomy
Subtotal or total abdominal colectomy
  • Resection of most of or the entire colon
Less commonly used techniques

Treatment of rectal cancertoggle arrow icon

Principles of rectal cancer treatment [9][34]

Treatment of rectal cancer by stage
AJCC Stage Treatment approach
Stage I
Stage II
Stage III
Stage IV

Surgery for rectal cancer [9]

  • The extent of the resection depends on the location of the tumor and the TNM stage.
  • The sphincter tone and the distance of the tumor from the anal verge (e.g., via rigid proctosigmoidoscopy) should be assessed preoperatively to plan appropriate surgical resection.
  • Consider gynecology and/or urology consult if imaging shows a regional spread past the rectum.
Typical surgeries for rectal cancer
Description Indication Tumor stage
Transanal excision
  • Minimally invasive excision of small superficial tumors
  • Early, localized disease (stage I)
Low anterior resection (LAR)
  • Sphincter-preserving resection of the rectum and sigmoid
  • Total mesorectal excision (TME)
  • Immediate reconstruction (e.g., side-to-side anastomosis)
  • Optional diverting ostomy
  • Tumor location allowing for sphincter preservation in patients with good preoperative sphincter function
    • Appropriate distal resection margins depend on the location of the tumor.
      • 5 cm for tumors of the upper third of the rectum
      • For tumors closer to the anal sphincter, smaller resection margins may be tolerated.
    • Shorter margins may be acceptable when neoadjuvant therapy has been successful.
  • Stage I tumors ineligible for transanal excision
  • Locally advanced disease (stages II–III)
  • Resectable metastatic disease (stage IV)

Abdominoperineal resection (APR)

  • Tumor too close to the sphincter to achieve an adequate distal margin without compromising the sphincter or cancer that has infiltrated the sphincter

A complete TME is necessary to adequately assess the nodal status and prevent recurrence.

Pathologytoggle arrow icon

Gross pathology


95% of all colorectal cancers are adenocarcinomas.

Complicationstoggle arrow icon

Peritoneal carcinomatosis [43][44]

We list the most important complications. The selection is not exhaustive.

Follow-uptoggle arrow icon

All patients with CRC should be followed up closely after curative treatment to ensure early identification and management of recurrence. These recommendations are consistent with the American Society of Colon and Rectal Surgeons' 2015 guidelines. [46][47][48]

90% of recurrences occur within the first five years following treatment. [48]

Prognosistoggle arrow icon

Screeningtoggle arrow icon

Screening modalities and screening intervals depend on individual risk factors and differ for individuals at average risk and those at high risk of CRC.

Individuals at average risk (general population) [21][49][50][51][52]

Individuals at high risk [21][49]

Colorectal cancer screening for high-risk individuals
High-risk characteristics Screening recommendations

History of adenomatous polyps

History of CRC

Positive family history

(Also consider genetic testing in patients with multiple affected family members or relatives affected at a young age)

≥ 2 first-degree relatives with CRC diagnosed at any age

  • Start screening with complete colonoscopy at age 40 or 10 years earlier than the index patient's age at diagnosis; whichever is earlier
  • Followed by complete colonoscopy every 5 years

≥ 1 first-degree relative with CRC or advanced adenoma diagnosed at < 60 years of age

≥ 1 first-degree relative with CRC or advanced adenoma diagnosed at ≥ 60 years of age

One second-degree relative with CRC or advanced adenoma

Other high-risk conditions

Hereditary syndromes associated with increased risk of CRC (e.g., FAP, HNPCC)
Inflammatory bowel disease

Primary preventiontoggle arrow icon

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Referencestoggle arrow icon

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