- Clinical science
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.
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
Epidemiological data refers to the US, unless otherwise specified.
- Colorectal adenomas (see )
- Family history
- Hereditary syndromes
- : 100% risk by age 40
- Hereditary nonpolyposis colorectal cancer (): 80% progress to CRC.
- Conditions associated with an increased risk of colorectal cancer
- Diet and lifestyle
- Alcohol consumption
- Processed meat; high-fat, low-fiber diets
- Older age
- Physical activity
- Diet rich in fiber and vegetables and lower in meat
- Long-term use of aspirin and other NSAIDs
- Often asymptomatic, particularly during the early stages of disease
- Nonspecific symptoms: constitutional symptoms (weight loss, fever, night sweats), fatigue, abdominal discomfort
- In general, right-sided tumors chronically bleed, and left sided tumors cause obstruction
Symptoms according to location
- Rectosigmoid > ascending colon > descending colon
- Right-sided carcinomas (10%): cecum and ascending colon
- Left-sided carcinomas (10%): transverse and descending colon
- Changes in bowel habits (size, consistency, frequency)
- Blood-streaked stools
- Colicky abdominal pain due to obstruction
- Rectum (50%) and sigmoid (30%)
Symptoms according to stage of disease
- Advanced disease
- Palpable abdominal mass
- Intestinal obstruction or perforation
- Metastatic disease: 20% of patients already have distant metastasis on initial diagnosis.
- Advanced disease
Colorectal cancer must be ruled out in a patient presenting with rectal bleeding, even if the patient has a history of hemorrhoids!
|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)|
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!
- Complete colonoscopy: gold standard
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
- Tumor marker: carcinoembryonic antigen (CEA) serum levels prior to initiating treatment
- Adenocarcinoma (most common): 95% arise from adenomatous polyps
- 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
- MLH-1 and MSH-2
- COX-2 overexpression: associated with colorectal cancer. Thus, the possible protective effect of long-term use of aspirin and other NSAIDs
95% of all colorectal cancers are adenocarcinomas!
- Diagnostics: ultrasound, ,
- Treatment: resection of the small bowel; R1 resection requires adjuvant chemotherapy
Prognosis (if malignant)
- 5-year survival rate: ∼ 20%
The differential diagnoses listed here are not exhaustive.
- 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
- Treatment involves palliative chemotherapy.
Colectomy: The extent of the resection depends on the location of the tumor.
- Open approach or laparoscopic approach
- Right hemicolectomy
- Left hemicolectomy
- Sigmoid colectomy
- Total abdominal colectomy: indicated for hereditary and multifocal carcinomas
- Regional lymph node dissection (for pathologic staging)
- Resection of resectable metastases in liver and/or lung
- Adjuvant chemotherapy if lymph nodes are positive (Stage III)
- Palliative chemotherapy for metastatic disease (Stage IV)
- Biologicals: Anti-VEGF antibodies (e.g., bevacizumab) or EGFR antibody (e.g., cetuximab) may be added to the chemotherapy regimen for metastatic disease.
- Radiation therapy: not a standard modality for treatment of colon cancer
- 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)
- Procedure: sphincter-preserving resection of the rectum and sigmoid
The completeness of the TME has a strong impact on the prognosis!
- Abdominoperineal resection (APR)
- Palliative procedures include transanal excision or diverting colostomy to facilitate defecation.
- 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)
- 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
- Patient history, physical examination, CEA level: every 3–6 months for 3 years, then every 6 months for 2 years
85% of recurrences occur within the first three years following treatment!
- Overall 5-year survival rate: 65%
- Survival rate according to disease stage
- Stage I: 95%
- Stage II: ∼ 80% 
- Stage III: 60%
- Stage IV: 5–10%
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
- 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 and for details)
|Surveillance following polypectomy|
|Histology of removed polyp||Recommended interval until next control colonoscopy|
| ||< 3 years; depends on the case (i.e., family history)|