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 . 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. 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).
- Incidence 
- Prevalence: ∼ 0.4%
- Mortality: third leading cause of cancer-related deaths in the US overall
Epidemiological data refers to the US, unless otherwise specified.
Colorectal carcinogenesis pathways (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
- Hypermethylation phenotype pathway in colon cancer
- COX-2 overexpression
Risk factors for colorectal cancer 
- Age: older age (> 40 years) 
- Family history: Approx. 25% of individuals with colorectal cancer (CRC) have a positive family history.
- : 100% of individuals will have developed CRC by the age of 40 years, Gardner syndrome, Turcot syndrome, Peutz-Jeghers syndrome, Juvenile polyposis syndrome)
- Hereditary nonpolyposis colorectal cancer (): progression to CRC in 80% of cases
- Associated conditions
- Alcohol consumption
- Processed meat
- High-fat and low-fiber
- Pathogens: Streptococcus bovis, Clostridium septicum
- Other: History of abdominal radiation during childhood
Protective factors 
Colorectal cancer can be asymptomatic, particularly during the early stages.
- Weight loss
- Night sweats
- Abdominal discomfort (symptoms similar to diverticulitis, especially in carcinoma of the rectosigmoid or descending colon)
Right-sided colon carcinomas 
- Definition: large bowel malignancies arising from the cecum, ascending colon, or transverse colon
- Clinical features
Left-sided colon carcinomas 
- Definition: large bowel malignancies arising from the splenic flexure, descending colon, sigmoid colon, or the rectosigmoid junction
- Changes in bowel habits (size, consistency, frequency)
- Blood-streaked stools
- Colicky abdominal pain (due to obstruction)
Rectal carcinomas 
- Definition: large bowel malignancies located ≤ 15 cm from the anal verge 
- Clinical features
Metastatic disease 
- Liver metastases (most common site of metastasis: ; 40–50%)
- Lung metastases
- Peritoneal metastases
- Evidence of distant lymphatic spread: Virchow node (rare) 
Red flags for colorectal cancer 
The sensitivity and specificity of symptoms of colorectal cancer are limited. The following features have the strongest association with CRC, especially in patients with , and should always prompt further investigation.
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 
- Indication: all patients with lower gastrointestinal bleeding (LGIB) or other
- DRE is a part of the routine clinical evaluation in patients with lower gastrointestinal symptoms.
- Endoscopic evaluation is essential if there is any suspicion for CRC, such as:
- Assess sphincter tone during DRE to plan optimal surgical resection for rectal cancer.
Flexible sigmoidoscopy with or without anoscopy 
Indication: Consider in patients with scanty intermittent hematochezia and all of the following features.
- Age < 40 years
- No other
- Important consideration: Patients who do not fulfill any of these criteria require a complete colonoscopy.
- Findings and next steps
- Indication: all patients with suspected CRC
Typical findings 
- Ulceroproliferative friable mass
- A biopsy is required to confirm the diagnosis (see “Pathology” section for details).
- Important considerations: Consider the following to identify colonoscopy cannot be completed (e.g., patients with occlusive CRC).  if
Double-contrast barium enema (uncommonly performed)
- Indication: an alternative to CT colonography in patients who decline/cannot undergo a complete colonoscopy at presentation
- Important considerations
All colorectal cancers: Assess for local and distant spread (T stage, N stage, and M stage). 
- CT abdomen, pelvis, and chest (with IV and oral contrast)
- Consider CTA or MRI of the liver if hepatic metastases are suspected.  
- Evaluate for specific sites of metastasis based on clinical suspicion (e.g., diagnostic laparoscopy and peritoneal cytology for suspected peritoneal metastasis). 
- Typical findings of distant metastasis
- Additional staging workup in rectal cancer 
Laboratory studies 
Carcinoembryonic antigen (CEA): Obtain baseline levels in all patients before initiating treatment. ; 
- Monitor CEA levels during treatment and follow-up to assess response to treatment and evaluate recurrence.
- Should not be used for screening 
- CBC: may show microcytic anemia (iron deficiency anemia)
- Liver chemistries and coagulation: may be abnormal in patients with multiple hepatic metastases
- Counseling and genetic testing: for patients < 50 years of age with CRC or those with a family history of CRC at a young age (see “ ” for details)
CEA is a prognostic marker and should not be used to screen for colorectal cancer.
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) ||TNM stage||Corresponding Dukes classification stage||Description|
|0|| || |
|II|| || |
|III|| || |
|IV|| || |
Differential diagnoses based on clinical presentation
- Differential diagnoses of
- Differential diagnoses of
- Differential diagnoses of
Small bowel neoplasms
- Prognosis (if malignant): 5-year survival rate is ∼ 68% 
The differential diagnoses listed here are not exhaustive.
General principles 
- A multidisciplinary approach is recommended.
- Treatment depends primarily on the location of the tumor and the TNM stage.
Surgery for colorectal cancer 
Surgery of primary tumor
- Indicated in any resectable primary tumor with no metastasis or resectable distant metastases
- Conventional or laparoscopic approach is possible 
- Complete resection with clear margins ( ) is associated with the best prognosis.
- See “Surgery for colon cancer” and “Surgery for rectal cancer” for details.
- Regional lymph node dissection: performed routinely alongside resection of the primary tumor
- Resection of metastases
Consider in patients with nonresectable distant metastases to prevent or treat complications of colorectal cancer.
- Intestinal bypass (e.g., ileocolonic anastomosis, colostomy) or enteral stenting for obstructing/occlusive CRC
- Tumor resection to manage immediately life-threatening complications, such as complete bowel obstruction, persistent GI bleeding, or perforation. 
Systemic therapy 
Systemic therapy is indicated in most patients with colon or rectal cancer. See “ ” and “ ” for details. 
- Chemotherapy regimens
Principles of colon cancer treatment 
|Treatment of colon cancer by stage|
|AJCC stage||Treatment approach|
|Stage I|| |
|Stage IV|| |
Surgery for colon cancer 
- Colectomy with lymph node dissection is indicated in all resectable tumors.
- The extent of the resection depends on the location of the tumor as well as the blood supply and lymphatic drainage of the affected region.
- En bloc resection of infiltrated adjacent tissue is recommended to obtain an R0 resection.
- In patients with peritoneal metastases, consider cytoreductive surgery in combination with intraperitoneal chemotherapy (HIPEC or hyperthermic intraperitoneal chemotherapy). 
- Bowel continuity should be restored via anastomosis when feasible; a stoma (temporary/permanent) may be needed. 
|Typical surgeries for colon cancer |
|Type of resection||Description||Indication|
|Extended right hemicolectomy|
|Sigmoid colectomy|| |
|Subtotal or total abdominal colectomy|| |
|Less commonly used techniques|
Principles of rectal cancer treatment 
|Treatment of rectal cancer by stage|
|AJCC Stage||Treatment approach|
|Stage I|| |
|Stage IV|| |
Surgery for rectal cancer 
- 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|
|Transanal excision|| || || |
|Low anterior resection (LAR)|| || || |
Abdominoperineal resection (APR)
A complete TME is necessary to adequately assess the nodal status and prevent recurrence.
- Right-sided colon carcinomas: mostly exophytic mass
- Left-sided colon carcinomas: mostly infiltrating mass
- Most common: adenocarcinoma (95%)
- Less common
95% of all colorectal cancers are adenocarcinomas.
Peritoneal carcinomatosis 
- Definition: a terminal feature of abdominal cancers (most commonly of the ovary, appendix, or colon) characterized by seeding of the tumor to the peritoneum
- Epidemiology: : depends on underlying malignancy; peritoneal carcinomatosis develops in ∼ 10% of individuals with colorectal cancer 
- Etiology: primary tumor metastasizes to the peritoneal surface
- Clinical features
- Diagnostics: CT is preferred; typically shows metastatic studding (tumor nodules studding the surface of the peritoneum) and omental caking
- Operable disease: involves cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC), systemic chemotherapy, targeted therapy, and/or immune checkpoint inhibitors
- Inoperable disease: experimental pressurized intraperitoneal aerosolized chemotherapy or repeated intraperitoneal chemotherapy infusion
- Complications: bowel, biliary, and/or ureteral obstruction
- Prognosis: : poor; 5-year survival rates after CRS and HIPEC are approx. 40%
We list the most important complications. The selection is not exhaustive.
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. 
Patient history, physical examination, CEA level
- Every 3–6 months for 2 years
- Every 6 months for an additional 3 years
- CT chest/abdomen/pelvis: annually for 5 years
- 1 year after preoperative colonoscopy
- Every 3–5 years in the further follow-up, depending on findings
- Recommended duration of close follow-up: 5 years following the completion of curative treatment
90% of recurrences occur within the first five years following treatment. 
Individuals at average risk (general population) 
- Criteria for average risk of CRC include:
Recommended screening age
- All individuals aged > 50 years; recent guidelines suggest starting screening at 45 years of age. 
- The decision to continue screening in patients aged > 75 years should be made on a case-by-case basis.
Screening modalities: Consider individual risk factors and patient preference when choosing a screening method.
- Direct visualization
- Stool-based testing
- Annual fecal immunochemical testing (FIT)
Annual fecal occult blood test (FOBT)
- Used to detect the presence of blood in feces that is not visibly apparent.
- Used as a screening tool for colorectal carcinoma, but upper gastrointestinal bleeding (e.g., from a peptic ulcer) can also yield positive results
- A positive result merits additional follow-up (e.g., upper endoscopy, colonoscopy)
- Has poor sensitivity for detecting polyps
- Multitargeted stool DNA test every 3 years
Individuals at high risk 
|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
|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|
- Control modifiable . 
- Long-term aspirin therapy may reduce the incidence of CRC. 
- Low-dose aspirin may be considered based on if all of the following parameters are met:
- Important considerations
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