- Clinical science
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.
- 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.
Risk factors 
- Age: older age
- Hereditary syndromes
- Associated conditions
- Alcohol consumption
- Processed meat
- High-fat and low-fiber
Protective factors 
- Often times asymptomatic, particularly during the early stages
Constitutional symptoms 
- Weight loss
- Night sweats
- Abdominal discomfort (symptoms similar to diverticulitis, especially in carcinoma of the rectosigmoid or descending colon)
Symptoms of right-sided carcinomas 
Symptoms of left-sided carcinomas 
- Changes in bowel habits (size, consistency, frequency)
- Blood-streaked stools
- Colicky abdominal pain (due to obstruction)
- Mostly infiltrating mass
Symptoms of rectal carcinomas 
- ↓ Stool caliber (pencil-shaped stool)
- Rectal pain
- Flatulence with involuntary stool loss
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
- Palpable abdominal mass
- Intestinal obstruction or perforation
Symptoms of metastatic disease 
|Stages of colorectal cancer|
|AJCC staging (simplified)||TNM stage||Corresponding Dukes classification stage||Description|
|I|| || |
|II|| || |
|III|| || |
|IV|| || |
Work-up of colorectal cancer is indicated in symptomatic patients and asymptomatic patients with abnormalities detected during routine screening.
- Digital rectal examination: Up to 10% of cancers are palpable.
- Gold standard
- Complete surveillance of the colon is mandatory
- Double-contrast barium enema 
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
- Most common: adenocarcinoma (95%)
- Less common
95% of all colorectal cancers are adenocarcinomas.
Molecular pathology 
- Chromosomal instability pathway in colon cancer: The adenoma-carcinoma sequence is the progressive accumulation of mutations in oncogenes (e.g., KRAS) and tumor suppressor genes (e.g., APC, TP53) that results in the slow transformation of adenomas into carcinomas.
- Microsatellite instability pathway in colon cancer: due to methylation or mutations in mismatch repair genes (MMR genes, e.g. MLH1 or MSH2)
- Hypermethylation phenotype pathway in colon cancer
- COX-2 overexpression
- Prognosis (if malignant): 5-year survival rate is ∼ 68% 
The differential diagnoses listed here are not exhaustive.
- Curative approach
- Palliative approach
- Extent of the resection depends on the location of the tumor
- Open approach or laparoscopic approach
- Right hemicolectomy
- Arterial blood supply: left colic artery arising from the inferior mesenteric artery
- Sigmoid colectomy
- Total abdominal colectomy: indicated for hereditary and multifocal carcinomas
Regional lymph node dissection
- Lymph nodes along the path of lymphatic drainage are resected.
- UICC requires the histological analysis of 12 removed lymph nodes to accurately define the lymph node status.
Resection of metastases in liver and/or lung
- In patients with limited metastatic disease, resection of liver and/or lung metastases may significantly improve survival.
- Enteral stenting
- Bypass (e.g., ileocolonic anastomosis)
- 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
Surgical management 
- Indication: early, localized disease (stage I)
- Procedure: minimally invasive excision of small superficial tumors
- 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.
- 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
- Indicated in locally advanced disease (stages II–III)
- Typically followed by surgery and postoperative chemotherapy
- Adjuvant chemotherapy: given after surgical resection depending on the pathologic work-up
- Palliative chemotherapy: for inoperable, metastatic disease (stage IV)
Screening for colorectal cancer and adenomatous polyps is performed in asymptomatic men and women ≥ 45 years of age.
- 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 
- CT colonography every 5 years
- 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 “ and “ )
|Surveillance following polypectomy|
|Histology||Recommended interval until next control colonoscopy|
> 10 adenomas
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
- 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.