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Colorectal Cancer

by Elliot M. Livstone, MD

Colorectal cancer (CRC) is extremely common. Symptoms include blood in the stool and change in bowel habits. Screening is with fecal occult blood testing. Diagnosis is by colonoscopy. Treatment is surgical resection and chemotherapy for nodal involvement.

CRC accounts for an estimated 137,000 cases and 50,000 deaths in the US annually. In Western countries, the colon and rectum account for more new cases of cancer per year than any anatomic site except the lung. Incidence begins to rise at age 40 and peaks at age 60 to 75. Overall, 70% of cases occur in the rectum and sigmoid, and 95% are adenocarcinomas. Colon cancer is more common among women; rectal cancer is more common among men. Synchronous cancers (more than one) occur in 5% of patients.

Etiology

CRC most often occurs as transformation within adenomatous polyps. Serrated adenomas are particularly aggressive in their malignant transformation. About 80% of cases are sporadic, and 20% have an inheritable component. Predisposing factors include chronic ulcerative colitis (see Ulcerative Colitis) and granulomatous colitis; 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, perineural spread, and intraluminal metastasis.

Symptoms and Signs

Colorectal adenocarcinoma grows slowly, and a long interval elapses before it is large enough to cause symptoms. Symptoms depend on lesion location, type, extent, and complications.

The right colon has a large caliber, 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 encircle the bowel, causing alternating constipation and increased stool frequency or diarrhea. 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

  • Colonoscopy

(See also the U.S. Preventive Services Task Force’s summary of recommendations regarding screening for colorectal cancer and the American College of Gastroenterology's current guideline Colorectal Cancer Screening for colorectal cancer screening and surveillance.)

Screening tests

  • Fecal occult blood testing

  • Flexible sigmoidoscopy

  • Colonoscopy

  • Sometimes CT colonography

Early diagnosis depends on routine examination, particularly fecal occult blood (FOB) testing. Several options are available, including traditional guaiac-based tests and newer immunochemical tests, which may be more sensitive and specific. Cancer detected by this method tends to be at an earlier stage and hence more curable. For average-risk patients, FOB testing should be done annually after age 50, with flexible sigmoidoscopy every 5 yr. Some authorities recommend colonoscopy every 10 yr instead of sigmoidoscopy. Colonoscopy every 3 yr may be even better. Screening of patients with high-risk conditions (eg, ulcerative colitis) is discussed under the specific condition.

CT colonography (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.


Diagnostic tests

  • Colonoscopic biopsy

  • CT to evaluate extent of tumor growth and spread

Patients with positive FOB tests require colonoscopy, as do those with lesions seen during sigmoidoscopy or 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 preferred as follow-up to a positive FOB 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 not specific and therefore is not recommended for screening. However, if CEA is high preoperatively and low after removal of a colon tumor, monitoring CEA may help to detect recurrence earlier. CA 19­9 and CA 125 are other tumor markers that may be similarly used.


Prognosis

Prognosis depends greatly on stage (see Staging Colorectal Cancer*). The 10-yr 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*

Stage

Tumor (Maximum Penetration)

Regional Lymph Node Metastasis

Distant Metastasis

0

Tis

N0

M0

I

T1 or T2

N0

M0

II

T3

N0

M0

III

Any T or

Any N

M0

T4

N0

M0

IV

Any T

Any N

M1

*TNM classification:

  • Tis =carcinoma in situ; T1 = submucosa; T2 = muscularis propria; T3 = penetrates all layers (for rectal cancer, includes perirectal tissue); T4 = adjacent organs or peritoneum.

  • N0 = none; N1 = 1–3 regional nodes; N2 = 4 regional nodes; N3 = apical or vascular trunk nodes.

  • M0 = none; M1 = present.

Treatment

  • Surgical resection, sometimes combined with chemotherapy, radiation, or both

Surgery

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. If there is 5 cm of normal bowel present between the lesion and the anal verge, an abdominoperineal resection is done, with permanent colostomy.

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 5-yr postoperative survival is 25%.


Adjuvant therapy

Chemotherapy (typically 5-fluorouracil and leucovorin) improves survival by 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 gaining favor.


Follow-up

Postoperatively, colonoscopy should be done annually for 5 yr and every 3 yr thereafter if no polyps or tumors are found. If preoperative colonoscopy was incomplete because of an obstructing cancer, a completion colonoscopy should be done 3 mo after surgery.

Additional screening for recurrence should include history, physical examination, and laboratory tests (eg, CBC, liver function tests) every 3 mo for 3 yr and then every 6 mo for 2 yr. Imaging studies (CT or MRI) are often recommended at 1-yr intervals but are of uncertain benefit for routine follow-up in the absence of abnormalities on examination or blood tests.


Palliation

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 mo. Some obstructing tumors can be debulked by endoscopic laser treatment or 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 CRC, 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, hepatic artery infusion with floxuridine or radioactive microspheres, given either intermittently in a radiology department or given continuously via an implantable sc 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.


Key Points

  • Colorectal cancer (CRC) is the 2nd most common cancer 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, change in stool frequency, colicky abdominal pain).

  • Routine screening should begin at age 50 for patients with average risk; typical methods involve fecal occult blood (FOB) testing and/or endoscopy.

  • 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.

Resources In This Article

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • CARAC
  • No US brand name
  • ELOXATIN
  • VECTIBIX
  • AVASTIN
  • XELODA
  • ERBITUX
  • CAMPTOSAR

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