Colorectal cancer accounts for an estimated 147,950 cases and 53,200 deaths in the US annually (1 General reference Colorectal cancer is extremely common. Symptoms include blood in the stool and change in bowel habits. Screening using one of several methods is recommended for appropriate populations. Diagnosis... read more ). Incidence rises sharply around age 40 to 50. Overall, more than half of the cases occur in the rectum and sigmoid, and 95% are adenocarcinomas. Colorectal cancer is slightly more common among men than women. Synchronous cancers (more than one) occur in 5% of patients.
Etiology of Colorectal Cancer
Colorectal cancer (CRC) most often occurs as transformation within adenomatous polyps Polyps of the Colon and Rectum An intestinal polyp is any mass of tissue that arises from the bowel wall and protrudes into the lumen. Most are asymptomatic except for minor bleeding, which is usually occult. The main concern... read more . About 80% of cases are sporadic, and 20% have an inheritable component. Predisposing factors include chronic ulcerative colitis Ulcerative Colitis Ulcerative colitis is a chronic inflammatory and ulcerative disease arising in the colonic mucosa, characterized most often by bloody diarrhea. Extraintestinal symptoms, particularly arthritis... read more and Crohn colitis Crohn Disease Crohn disease is a chronic transmural inflammatory bowel disease that usually affects the distal ileum and colon but may occur in any part of the gastrointestinal tract. Symptoms include diarrhea... read more ; the risk of cancer increases with the duration of these disorders.
Patients in populations with a high incidence of CRC eat low-fiber diets that are high in animal protein, fat, and refined carbohydrates. Carcinogens may be ingested in the diet but are more likely produced by bacterial action on dietary substances or biliary or intestinal secretions. The exact mechanism is unknown.
CRC spreads by direct extension through the bowel wall, hematogenous metastasis, regional lymph node metastasis, and perineural spread.
Symptoms and Signs of Colorectal Cancer
Colorectal adenocarcinomas grow slowly, and a long interval elapses before they are large enough to cause symptoms. Symptoms depend on lesion location, type, extent, and complications.
The right colon has a large caliber and a thin wall and its contents are liquid; thus, obstruction is a late event. Bleeding is usually occult. Fatigue and weakness caused by severe anemia may be the only complaints. Tumors sometimes grow large enough to be palpable through the abdominal wall before other symptoms appear.
The left colon has a smaller lumen, the feces are semisolid, and cancer tends to cause obstruction earlier than in the right colon. Partial obstruction with colicky abdominal pain or complete obstruction may be the initial manifestation. The stool may be streaked or mixed with blood. Some patients present with symptoms of perforation, usually walled off (focal pain and tenderness), or rarely with diffuse peritonitis.
In rectal cancer, the most common initial symptom is bleeding with defecation. Whenever rectal bleeding occurs, even with obvious hemorrhoids or known diverticular disease, coexisting cancer must be ruled out. Tenesmus or a sensation of incomplete evacuation may be present. Pain is common with perirectal involvement.
Some patients first present with symptoms and signs of metastatic disease (eg, hepatomegaly, ascites, supraclavicular lymph node enlargement).
Diagnosis of Colorectal Cancer
Fecal occult blood testing
Sometimes flexible sigmoidoscopy
Sometimes fecal DNA testing
Sometimes CT colonography
For average-risk patients, screening for colorectal cancer (CRC) should begin at age 45 years and continue until age 75 years. For adults aged 76 to 85, the decision whether to screen for CRC should be individualized, taking into consideration the patient's overall health and prior screening history (see also the U.S. Preventive Services Task Force's 2021 recommendation statement for screening for colorectal cancer and the American College of Gastroenterology’s [ACG] clinical guidelines for colorectal cancer screening).
There are multiple options for CRC screening, including
Colonoscopy every 10 years
Fecal occult blood test annually (fecal immunochemical tests [FIT] preferred)
Flexible sigmoidoscopy every 5 years (every 10 years if combined with FIT)
CT colonography every 5 years
Fecal DNA testing combined with FIT every 3 years
The ACG colorectal cancer screening guidelines recommend colonoscopy every 10 years or annual FIT as the preferred screening tests. Alternative CRC screening tests are available for patients who decline colonoscopy or for whom economic issues preclude screening with colonoscopy and for whom the need for repeated testing with FIT is problematic. Patients with a family history of a 1st-degree relative with colorectal cancer diagnosed prior to age 60 should undergo colonoscopy every 5 years, beginning at age 40 years, or 10 years before the age the relative was diagnosed, whichever comes first. Screening of patients with high-risk conditions (eg, ulcerative colitis Diagnosis Ulcerative colitis is a chronic inflammatory and ulcerative disease arising in the colonic mucosa, characterized most often by bloody diarrhea. Extraintestinal symptoms, particularly arthritis... read more ) is discussed under the specific condition.
Fecal immunochemical tests for blood are more sensitive and specific for human blood than older guaiac-based stool tests, which can be affected by many dietary substances. However, a positive test for blood can result from nonmalignant disorders (eg, ulcers, diverticulosis), and a negative test does not rule out cancer because cancers do not bleed continuously.
Fecal DNA testing detects DNA mutations and methylation markers shed from a colonic tumor. The test typically is combined with FIT, and the combined test is approved for screening average-risk patients. Patients with a positive fecal DNA-FIT test should get a follow-up colonoscopy within 6 months to reduce the risk of missing advanced colon cancer. Nearly 10% of patients with a positive fecal DNA-FIT test result have a normal colonoscopy; such patients can have a repeat fecal DNA-FIT test in 1 year or a repeat colonoscopy in 3 years. If these tests are negative, they can return to the average-risk colon cancer screening schedule.
CT colonography CT colonography X-ray and other imaging contrast studies visualize the entire gastrointestinal tract from pharynx to rectum and are most useful for detecting mass lesions and structural abnormalities (eg, tumors... read more (virtual colonoscopy) generates 3D and 2D images of the colon using multidetector row CT and a combination of oral contrast and gas distention of the colon. Viewing the high-resolution 3D images somewhat simulates the appearance of optical endoscopy, hence the name. It has some promise as a screening test for people who are unable or unwilling to undergo endoscopic colonoscopy but is less sensitive and highly interpreter-dependent. It avoids the need for sedation but still requires thorough bowel preparation, and the gas distention may be uncomfortable. Additionally, unlike with optical colonoscopy, lesions cannot be biopsied during the diagnostic procedure.
Video capsule endoscopy of the colon has many technical problems and is not currently acceptable as a screening test.
Blood-based tests (eg, Septin 9 assay) have been approved for screening average-risk patients but are not widely used because of inadequate sensitivity.
CT to evaluate extent of tumor growth and spread
Patients with positive fecal occult blood tests require colonoscopy, as do those with lesions seen during sigmoidoscopy or an imaging study. All lesions should be completely removed for histologic examination. If a lesion is sessile or not removable at colonoscopy, surgical excision should be strongly considered.
Barium enema x-ray, particularly a double-contrast study, can detect many lesions but is somewhat less accurate than colonoscopy and is not currently acceptable as follow-up to a positive fecal occult blood test.
Once cancer is diagnosed, patients should have abdominal CT, chest x-ray, and routine laboratory tests to seek metastatic disease and anemia and to evaluate overall condition.
Elevated serum carcinoembryonic antigen (CEA) levels are present in 70% of patients with CRC, but this test is neither sensitive nor specific and therefore is not recommended for screening. However, if the CEA level is high preoperatively and low after removal of a colon tumor, monitoring the level may help detect recurrence earlier. CA 19-9 and CA 125 are other tumor markers that may be similarly used.
Colon cancers that were removed during surgery are now routinely tested for the gene mutations that cause Lynch syndrome Lynch Syndrome Lynch syndrome is an autosomal dominant disorder responsible for 2 to 3% of cases of colorectal cancer. Symptoms, initial diagnosis, and treatment are similar to other forms of colorectal cancer... read more . People with relatives who developed colon, ovarian, or endometrial cancer at a young age or who have multiple relatives with those cancers should be tested for Lynch syndrome.
Prognosis for Colorectal Cancer
Prognosis depends greatly on stage (see Table: Staging Colorectal Cancer* Staging Colorectal Cancer* ). The 5-year survival rate for cancer limited to the mucosa approaches 90%; with extension through the bowel wall, 70 to 80%; with positive lymph nodes, 30 to 50%; and with metastatic disease, < 20%.
Staging Colorectal Cancer*
Tumor (Maximum Penetration)
Regional Lymph Node Metastasis
T1 or T2
Any T or
* TNM classification:
Treatment of Colorectal Cancer
Surgical resection, sometimes combined with chemotherapy, radiation, or both
Surgery for cure can be attempted in the 70% of patients presenting without metastatic disease. Attempt to cure consists of wide resection of the tumor and its regional lymphatic drainage with reanastomosis of bowel segments.
For rectal cancer, sphincter-saving surgical resection can be done in patients with rectal cancer that has a distal margin of ≥ 1.0 cm, instead of the usual 5-cm length, without significant risk of local recurrence or decreased long-term survival. Sphincter-saving procedures have been done in patients with rectal cancer that has a distal margin of < 1cm, but these patients have an increased risk of local recurrence and decreased long-term survival. The problem with sphincter-saving procedures is often more functional (eg, fecal leakage, incontinence) in nature rather than oncologic (eg, local recurrence, decreased survival). If there is local recurrence or poorly tolerated bowel function after a sphincter-saving procedure, then an abdominoperineal resection (APR) with permanent colostomy (1 Treatment references Colorectal cancer is extremely common. Symptoms include blood in the stool and change in bowel habits. Screening using one of several methods is recommended for appropriate populations. Diagnosis... read more ) is done.
With liver metastases, resection of a limited number (1 to 3) of liver metastases is recommended in select nondebilitated patients as a subsequent procedure. Criteria include patients whose primary tumor has been resected, whose liver metastases are in one hepatic lobe, and who have no extrahepatic metastases. Only a small number of patients with liver metastases meet these criteria, but in such cases 5-year postoperative survival is 25%.
Chemotherapy improves survival by at least 10 to 30% in colon cancer patients with positive lymph nodes. Rectal cancer patients with 1 to 4 positive lymph nodes benefit from combined radiation and chemotherapy; when > 4 positive lymph nodes are found, combined modalities are less effective. Preoperative radiation therapy and chemotherapy to improve the resectability rate of rectal cancer or decrease the incidence of lymph node metastasis are standard.
After curative surgical resection of colorectal cancer, surveillance colonoscopy should be done 1 year after surgery or after the clearing preoperative colonoscopy (2 Treatment references Colorectal cancer is extremely common. Symptoms include blood in the stool and change in bowel habits. Screening using one of several methods is recommended for appropriate populations. Diagnosis... read more ). A second surveillance colonoscopy should be done 3 years after the 1-year surveillance colonoscopy if no polyps or tumors are found. Thereafter, surveillance colonoscopy should be done every 5 years. If the preoperative colonoscopy was incomplete because of an obstructing cancer, a completion colonoscopy should be done 3 to 6 months after surgery to detect any synchronous cancers and to detect and resect any precancerous polyps (2 Treatment references Colorectal cancer is extremely common. Symptoms include blood in the stool and change in bowel habits. Screening using one of several methods is recommended for appropriate populations. Diagnosis... read more ).
Additional screening for recurrence should include history, physical examination, and serum carcinoembryonic antigen levels every 3 months for 3 years and then every 6 months for 2 years. Imaging studies (CT or MRI) are often recommended at 1-year intervals but are of uncertain benefit for routine follow-up in the absence of abnormalities on examination or blood tests.
When curative surgery is not possible or the patient is an unacceptable surgical risk, limited palliative surgery (eg, to relieve obstruction or resect a perforated area) may be indicated; median survival is 7 months. Some obstructing tumors can be debulked by electrocoagulation or held open by stents. Chemotherapy may shrink tumors and prolong life for several months.
Newer drugs used singly or in drug combinations include capecitabine (a 5-fluorouracil precursor), irinotecan, and oxaliplatin. Monoclonal antibodies such as bevacizumab, cetuximab, and panitumumab are also being used with some effectiveness. No regimen is clearly more effective for prolonging life in patients with metastatic colorectal cancer, although some have been shown to delay disease progression. Chemotherapy for advanced colon cancer should be managed by an experienced chemotherapist who has access to investigational drugs.
When metastases are confined to the liver but cannot be surgically resected, hepatic artery infusion with floxuridine or radioactive microspheres, given either intermittently in a radiology department or given continuously via an implantable subcutaneous pump or an external pump worn on the belt, may offer more benefit than systemic chemotherapy; however, these therapies are of uncertain benefit. When metastases are also extrahepatic, intrahepatic arterial chemotherapy offers no advantage over systemic chemotherapy. For selected patients with ≤ 3 liver lesions, stereotactic radiation therapy or thermal ablation using radiofrequency or microwave treatments can be considered.
1. Bujko K, Rutkowski A, Chang GJ, et al: Is the 1-cm rule of distal bowel resection margin in rectal cancer based on clinical evidence? A systematic review. Ann Surg Oncol 19(3):801–808, 2012. doi: 10.1245/s10434-011-2035-2
2. Kahi CJ, Boland R, Dominitz JA, et al: Colonoscopy surveillance after colorectal cancer resection: Recommendations of the US multi-society task force on colorectal cancer. Gastroenterology 150:758–768, 2016. doi: 10.1053/j.gastro.2016.01.001
Colorectal cancer is one of the most common cancers in western countries, typically arising within an adenomatous polyp.
Right-sided lesions usually manifest with bleeding and anemia; left-sided lesions usually manifest with obstructive symptoms (eg, colicky abdominal pain).
Routine screening should begin at age 45 for patients with average risk; typical methods involve colonoscopy or annual fecal occult blood testing and/or flexible sigmoidoscopy.
Serum carcinoembryonic antigen (CEA) levels are often elevated but are not specific enough to be used for screening; however, after treatment, monitoring CEA levels may help detect recurrence.
Treatment is with surgical resection, sometimes combined with chemotherapy and/or radiation; outcome varies widely depending on the stage of the disease.
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