American College of Physicians: Internal Medicine — Doctors for Adults ®

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Colorectal cancer

From the May ACP Observer, copyright 2006 by the American College of Physicians.

With colorectal cancer, early detection—usually before any symptoms occur—correlates with curability. Research has concluded that screening for colon cancers and adenomatous polyps is cost-effective. But here's where matters become complicated: Evidence does not yet support recommending one screening test over another.

To resolve that dilemma, said Randall W. Burt, FACP, interim executive director of the Huntsman Cancer Institute at the University of Utah in Salt Lake City and author of the PIER module on colon cancer, internists should select a screening method to use for each individual patient and then conscientiously stick to it.

"Our motto is, 'the best screening test is the screening test that gets done,' " Dr. Burt said. If you offer to screen 1,000 patients and 900 of them opt for a fecal occult blood test (FOBT), "even though it is not a very good test," he said, "you will save a lot more lives than if you offer them colonoscopy and only 100 of them get colonoscopy or have insurance that will pay for it."

Screening rates hover around 50%, he said—significantly better than the 30% that was common not that long ago. "But we would like it to be 90% or 100%." Colorectal cancer remains the fourth most common malignancy in the U.S. and the second most common cause of cancer death.

Although the intervals recommended for repeat colonoscopy screening are largely arbitrary, experts accept them because it takes a prolonged period of time, estimated at 10 years, for a polyp to progress from adenoma to carcinoma. The most cost-effective screening strategy appears to be either FOBT plus flexible sigmoidoscopy or colonoscopy—but to be even modestly effective, Dr. Burt pointed out, FOBT screening should be done annually.

This edition of ACP Observer Special Focus is designed to help optimize your ability to screen for, diagnose, treat and manage patients with colon cancer.

SCREENING AND PREVENTION

Because 93% of all colorectal cancers occur after age 50, screen all adults older than age 50 for colon cancer and adenomatous polyps. Begin earlier if the patient has a family history of colon cancer.


A cancer of the ascending colon, shown here by colored barium enema X-ray. The tumor appears as the oval shadow, at left, over the right pelvic bone.



Know your definitions. "Average risk" is defined as risk in patients over age 50 with no colorectal cancer family history. These individuals have a 5% lifetime risk of developing colorectal cancer. Seventy-five percent of new cases occur in people with no known predisposition to the disease.

People at "moderate risk" have a first-degree relative with colon cancer over age 50. The lifetime risk of patients in this category is two- to three-fold that of average-risk patients. "High-risk" individuals are defined as those with a first-degree relative diagnosed with colon cancer under age 50, or two first-degree relatives with colon cancer.

Such patients have a three- to four-fold increased risk of colon cancer compared to average-risk patients. A small subgroup of those at high risk will have one of the defined inherited syndromes of colon cancer, including familial adenomatous polyposis (FAP) or hereditary nonpolyposis colorectal cancer (HNPCC), also called Lynch syndrome. Other high-risk groups include patients with ulcerative colitis or Crohn's pancolitis.

For patients with an average risk of developing colon cancer, recommend one of the following screening regimens:

  • Annual fecal occult blood testing (FOBT). Prospective studies show a 33% mortality rate reduction from annual FOBT and between 15% and 18% with biennial testing.

  • Flexible sigmoidoscopy every five years. Sigmoidoscopy screening can reduce the incidence of left-sided colon cancer by between 60% and 70%, but limitations exist. Those include poor patient preparation that limits the examination in 10% of cases; variable provider skill, with adequate experience requiring between 24 and 30 examinations; and patient discomfort, which prevents the entire sigmoid from being examined in nearly one-quarter of cases.

  • Annual FOBT plus flexible sigmoidoscopy every five years. This combination increases the sensitivity for detecting neoplasia over FOBT or sigmoidoscopy alone, but patient compliance is lower and tends to decline over time.

  • Colonoscopy every 10 years. Although highly sensitive and specific, colonoscopy can miss 12% of small polyps, and detection rates depend on endoscopists' skill. Detection rates of adenomas and carcinomas are higher with colonoscopy than with FOBT or flexible sigmoidoscopy.

  • Double contrast barium enema every five-10 years. Some professional organizations recommend double contrast barium enema as a screening option. There are, however, no studies of its effectiveness in decreasing mortality.

Newer screening modalities such as virtual colonoscopy and stool DNA testing also lack sufficient data to recommend routinely. (For more on emerging screening methods, see "Screening innovations.")

Persons with moderate risk of colon cancer should have one of the screening approaches listed above, but beginning at age 40. Those at high risk should have colonoscopy every five years, beginning at age 40—or 10 years earlier than the youngest age at diagnosis in relatives.

A gastroenterologist should be consulted for even more aggressive screening in patients with possible FAP, HNPCC or inflammatory bowel disease.

If polyps are found during screening, follow up with another colonoscopy three years after complete removal of any adenomatous polyp 1 cm or larger. If the polyp is smaller than 1 cm in diameter, follow-up colonoscopy can be done in five years. Removing polyps decreases colon cancer risk by between 70% and 90% when compared to risk in patients with polyps that were not removed.

In terms of prevention, advise all patients to eat a diet high in fresh fruits and cruciferous vegetables and moderate in red meat and fat, and to participate in regular physical activity. The literature also suggests that other substances may decrease risk but require further study. These include calcium and vitamin D, folate and antioxidants. Postmenopausal estrogen supplements may also be protective but may increase cardiovascular risk.

DIAGNOSIS

Signs and symptoms alone are often nonspecific. Each of these signs and symptoms (except rectal mass) is less than 5% sensitive and specific for colon cancer:

  • rectal bleeding
  • change in bowel habits
  • hypogastric abdominal pain
  • abdominal distention
  • nausea and vomiting
  • pelvic pain or tenesmus
  • weight loss
  • abdominal tenderness
  • rectal or abdominal mass
  • hepatomegaly
  • fatigue

By the time symptoms develop, they may represent locally advanced or metastatic, often incurable, disease. (Rectal bleeding, either visible or occult, is associated with a slightly better prognosis than the other signs and symptoms listed.)

In patients with signs or symptoms, particularly in those over age 40, perform a full colon exam, preferably with colonoscopy to allow concurrent biopsy. Regardless of signs and symptoms, send any patient older than age 40 with a positive screening test for colon cancer for colonoscopy and possible biopsy.

Also refer to colonoscopy any patient with iron deficiency anemia not clearly and completely explained by other diagnoses. If the test fails to find colon lesions, obtain an upper GI and possibly a small bowel study.

TREATMENT

The most important factor in determining a course of treatment is disease stage. (See "Staging systems for colorectal cancer: a comparison.") Although staging is most accurate at the time of surgery—particularly to determine nodal involvement--clinical preoperative staging using radiologic studies can be useful to guide the surgical approach, determine the need for post-surgical radiation and chemotherapy, and help develop follow-up regimens.

Non-drug therapy

The mainstay of colon cancer treatment is prompt surgery, followed by chemotherapy in advanced-stage patients and radiation therapy in selected patients with rectal cancer. Even in patients with widespread metastases, surgical resection of the primary tumor can prevent obstruction from left colon primaries and bleeding from right-sided lesions.

Recommend surgical resection of the tumor for potential cure in stage I and II colorectal disease. Treat stage III tumors with resection of the tumor mass and adjuvant chemotherapy. Stage IV patients are treated with combined chemotherapy and sometimes surgery.

Radiation therapy can reduce recurrence and death in many rectal cancers beyond stage I when added to surgery and chemotherapy. Preoperative (neoadjuvant) radiation therapy can also decrease surgical mortality, surgical complications and the need for colostomy for selected stage II and III rectal cancers. Although adjuvant radiation therapy is not used outside the rectum, it can help with pain control of metastasis to bone, brain and the presacral area.

Advise patients that surgical treatment and staging usually require hospitalization for five to 10 days, and that they can expect to be out of work for four to six weeks. Placing an ileostomy or colostomy sometimes requires a second operation. Low rectal cancer may require colostomy, but cancer above the rectum—even 5 cm from the anus—does not usually require a colostomy.

Some patients may experience sexual dysfunction after rectal surgery and may need sex therapy; others will have disease-related anxiety or depression and can benefit from psychological or psychiatric therapy. Patients with a colostomy may need specialized enterostomy care.

Drug therapy

Although experts debate the benefit of adjuvant chemotherapy for stage II disease, consider chemotherapy for disease that penetrates the bowel wall.

In patients with stage III colon cancer, adjuvant chemotherapy can reduce five-year mortality by 22%. One common regimen is 5-fluorouracil plus leucovorin, given for five consecutive days once a month for six months, with reevaluation after one year. Adding oxaliplatin improves three-year disease-free survival.

For patients with stage IV (metastatic) colon and rectal cancer, multiagent chemotherapy with oxaliplatin or irinotecan plus a fluoropyrimidine—as well as the anti-angiogenesis agent bevacizumab—can decrease tumor burden and prolong survival. Consider using all active agents in combination and/or sequence to maximize patient survival.

In patients with metastases only to the liver, systemic chemotherapy may reduce tumor size enough to allow curative resection. Fully ambulatory, minimally symptomatic patients tolerate this treatment the best and benefit the most.

FOLLOW-UP

In patients who have undergone initial surgical resection of colon cancer, ask them about the following signs and symptoms:

  • symptoms of small or large bowel obstruction
  • hepatic capsular pain
  • jaundice
  • dyspnea
  • localized bone pain
  • neurological symptoms
  • asthenia
  • anorexia, nausea, weight loss

In those who have had surgical resection of rectal cancer, look for:

  • rectal bleeding
  • mucous discharge
  • altered bowel habits or straining at stool
  • pelvic pain
  • urinary difficulties

Measure carcinoembryonic antigen levels every three months for between two and three years to detect any increase over initial post-surgical levels, suggesting recurrence or metastases. Although there are few data supporting specific follow-up regimens, some experts also recommend annual liver function tests, chest radiographs, and abdominal or pelvic CT scans.

Stage I and II cancers: For all patients with stage I and II cancers, schedule follow-up colonoscopy after one and three years. Look for synchronous adenomatous polyps and new colon cancers. Adenomas recur in between 30% and 40% of patients after three years, and removing polyps decreases cancer incidence by between 70% and 90%. If that first colonoscopy turns up multiple adenomas, subsequent colonoscopy should be scheduled every three years; if not, every five years.

Stage III cancer: Because 40% of stage III patients who have chemotherapy will develop recurrent disease, follow these patients closely. Cancer recurs most commonly at the site of initial resection, then at hepatic, lung, bone and brain sites.

Obtain a colonoscopy at one and three years to examine the anastomotic site and to look for new neoplasms. If metastases are present, categorize the patient as now having "advanced disease." In addition, see patients six and 12 months after surgery and then annually for at least five years.

Monitor symptoms and carcinoembryonic antigen level. Consider obtaining liver function tests and chest radiographs as clinically indicated.

Stage IV cancer and "advanced disease": About 20% of patients with colorectal cancer will have "advanced disease," either at initial presentation or thereafter if they experience recurrence or metastases. Recurrent or metastatic disease develops in about one-half of all patients treated with curative surgery, often within three years of the original surgery. About one-half of patients with advanced disease will have liver metastasis.

If you detect local recurrence or a single or a small number of liver metastases, consider referring patients for resection of the detected lesion. Surgery is appropriate in about 5% of patients with metastasis in the liver and can result in a five-year survival rate of between 25% and 35%.

If salvage surgery isn't possible, provide palliation with newer chemotherapy and radiation protocols. Chemotherapy relieves symptoms in up to 30% of patients, and radiation therapy can alleviate pain, decrease bleeding and reduce straining in some advanced rectal cancers. Radiation can also alleviate symptoms in some patients with bone, liver and CNS metastases.

This information comes from two PIER modules: "Colon Cancer" and "Screening for Colorectal Cancer."

The information included herein should never be used as a substitute for clinical judgment and does not represent an official position of ACP.

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Screening innovations

In the search for a better screening method—one at least as accurate as colonoscopy but less expensive and more acceptable to patients—virtual colonoscopy and stool DNA testing are the most promising.

"They are not ready for prime time," said gastroenterologist Randall W. Burt, FACP, one of the nation's leading authorities on high-risk colon cancers, "but they are getting closer."

Dr. Burt talked to Special Focus about their pros and cons:

Virtual colonoscopy

When done in controlled studies and expert centers, CT colonoscopy is as accurate at detecting large polyps (the ones associated with cancer risk) as regular colonoscopy. But when done in community settings, "the accuracy goes down to unacceptable levels," Dr. Burt said. Another hurdle: Very few, if any, insurance companies will pay for the test.

Researchers are now working to figure out how virtual colonoscopy could be done without requiring patients to clean out their bowel first, by allowing the scan to erase the stool electronically, for instance.

"With the right hardware and software, we will be able to do that," Dr. Burt said. "Then it will become a good test."

Stool DNA testing

The sensitivity of this test, which examines mutations in the DNA of cellular debris in stool, is significantly better than that of fecal occult blood testing (FOBT)—about 50%—or one-time use. But when FOBT is done annually, it can reach a 50% sensitivity rate after four or five years. And FOBT costs significantly less: $10 compared to about $800, Dr. Burt said.

"If they could get the DNA tests' costs down to a couple hundred dollars or if they could get the sensitivity up to 70-80%, then maybe it would get to the point where it is a usable test," Dr. Burt said. Both of those developments should take place, he added, within the next few years.

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