Immunochemistry Tops Guaiac Test for Detecting Fecal Occult Blood

OAKLAND, Calif., Sept. 25 -- An immunochemistry test for fecal occult blood is significantly more accurate in detecting left-sided colorectal cancer than conventional testing, investigators here reported.

The fecal immunochemistry test had 82% sensitivity for left-sided colorectal cancer versus 64.3% with an enhanced-sensitivity guaiac test, James E. Allison, M.D., of Kaiser Permanente Northern California Region, and colleagues reported in the Sept. 25 issue of the Journal of the National Cancer Institute.

Combining the two tests yielded an overall accuracy that was no better than that of the guaiac test. The immunochemistry test and guaiac test both had a specificity exceeding 90%, and the immunochemistry test's specificity approached 100%.

"The superior sensitivity for cancer demonstrated by [a fecal immunochemistry test] has important implications for current and future screening program recommendations because a program of annual testing with the less sensitive guaiac test and sigmoidoscopy every 5 years has been shown to be as effective-regardless of cost-as a program of colonoscopy screening at the individual patient level," the authors stated.

"Therefore, annual fecal occult blood testing alone with an [immunochemistry test] that is as sensitive [as the one used in this study] might also be competitive with a colonoscopy screening program," they added.

Although fecal occult blood screening decreases the incidence and mortality of colorectal cancer, the currently used unrehydrated guaiac test has a sensitivity of only 24% for advanced colonic neoplasms, the authors noted. Moreover, the test is frequently not used as recommended in primary care settings.

The unrehydrated test detects peroxidase activity of heme, which is found in abundance in red meat, and many types of vegetables have substantial peroxidase activity, the researchers noted. Consequently, the unrehydrated guaiac test has considerable potential for false-positive results.

The search for a better fecal occult blood test led to the development of a sensitive guaiac test that could detect lower levels of peroxidase activity compared with the unrehydrated test. The search also has produced several fecal immunochemistry tests, which use antibodies specific to human hemoglobin, albumin, or other blood components.

But the relative accuracy of the sensitive guaiac test and immunochemistry tests had not been extensively evaluated in head-to-head comparisons.

So, in the current study, investigators prospectively screened 5,841 patients with an average risk for colorectal cancer. Each patient was screened with all three tests: the fecal immunochemistry test, the sensitive guaiac test, and both tests together.

Patients with positive test results from any of the screens were advised to have a colonoscopy. For those with negative results, flexible sigmoidoscopy was recommended.

The primary endpoint of the study was the sensitivity and specificity of the tests for detecting advanced neoplasms in the left colon within two years of screening (14 cancers, 128 adenomas). During follow-up, 139 patients were diagnosed with advanced colorectal cancer within two years of their initial fecal occult blood test.

In addition to its superior sensitivity, the immunochemistry test had a sensitivity of 96.9% versus about 90% for the sensitive guaiac test and 98% for combination testing. Sensitivity for detecting advanced colorectal adenomas was 41.3% for the sensitive guaiac, 29.5% for the immunochemistry test, and 22.8% for the combination.

In an editorial that accompanied the study report, Jack S. Mandel, Ph.D., of Emory University in Atlanta, noted that several fecal immunochemistry tests are commercially available, and the best choice among them, if one exists, has yet to be determined.

Even so, he added, the results show that "an immunochemical test is probably better than a guaiac test for screening for colorectal cancers."

Durado D. Brooks, M.D., director of prostate and colorectal cancer at the American Cancer Society in Atlanta, noted that immunochemical tests for fecal occult blood have been "recognized and recommended as a testing option by the American Cancer Society in our colorectal cancer screening guidelines since 2003."

"The current study adds important information to the literature around colorectal cancer screening with stool tests for occult blood through a head-to-head comparison of one type of fecal immunochemical test against a sensitive guaiac-based test," Dr. Brooks added.

"This is the largest trial of this type in a true screening population, and is also the largest such study to examine the possible utility of CRC screening utilizing a combination of different types of fecal occult blood tests," he said.