Stool Testing
Guaiac-Based Fecal Occult Blood Testing (gFOBT) Annually
There are currently two commercially available methods for testing stool for occult blood: the guaiac-based tests (gFOBT) and immunochemical-based tests (FIT). Guaiac-based tests detect hemoglobin through the pseudoperoxidase activity of heme. Therefore, these tests are not specific for lower intestinal bleeding or even for human blood. The immunochemical-based tests react to human globin and therefore do not require the same dietary restrictions recommended for the guaiac-based fecal occult blood testing. Stool tests for occult blood are designed to detect cancers that may bleed periodically. The goal is to detect these cancers at an early stage that is amenable to therapy and thereby decrease mortality from colorectal cancer. Stool tests are not particularly effective in detecting precancerous polyps, particularly those under 1 cm to 2 cm in size.
There have been prospective randomized controlled trials demonstrating that guaiac-based tests reduce mortality from colorectal cancer by 15% to 33% [A]. The Minnesota Colon Cancer Control Study [A] also noted a 20% decline in the incidence of colorectal cancer after 18 years of follow-up, presumably because of the detection and removal of polyps in those undergoing colonoscopy for evaluation of a positive stool guaiac test.
There is considerable variability reported in the literature on the sensitivity and specificity of available guaiac-based stool tests. The reported sensitivity for detecting colorectal cancer with a single guaiac-based stool test ranges from 12.9% to 79.4% [C]. Tests with high sensitivity (such as Hemoccult SENSA) are preferred over lower sensitivity tests (such as Hemoccult II) to detect as many occult colorectal cancers as possible. Rehydration of guaiac-based fecal occult blood testing is not recommended because of the increase in false-positives and the impact hydration has on the ability to accurately read the test. Testing stool obtained on rectal exam is not an acceptable form of colorectal cancer screening as this has the potential to miss over 90% of colorectal cancers [C].
Patients using a high sensitivity guaiac-based fecal occult blood tests are generally instructed to avoid non-steroidal anti-inflammatory medications and more than one aspirin per day for seven days prior to testing. To avoid false-positive results from dietary factors the manufacturer of Hemoccult SENSA also recommends patients avoid red meat (beef, lamb and liver) for three days prior to testing and on the day of testing. In addition, vitamin C in excess of 250 mg per day should not be consumed for three days prior to testing or on the day of testing. Vitamin C can interfere with the pseudoperoxidase reaction, resulting in a false-negative test. Patients are instructed to collect two samples from three separate bowel movements for testing.
Advantages of guaiac-based fecal occult blood test are that it is readily available in most clinical settings and there is minimal risk to the patient when performing the test. Providers and patients need to be aware that studies demonstrating a reduction in colorectal cancer mortality with guaiac-based fecal occult blood testing followed a program of annual testing over an extended period of time with colonoscopic evaluation of all positive results. Patients choosing to do guaiac-based fecal occult blood test for colorectal cancer screening should do this annually and be willing to have a colonoscopy if any guaiac-based fecal occult blood testing is positive. Repeat stool testing after a positive guaiac-based fecal occult blood testing is not appropriate nor is follow up with a test other than colonoscopy.
Fecal Immunochemical Testing (FIT) Annually
Immunochemical stool tests to detect occult blood in stool use one or more monoclonal antibodies to human globin. These tests were developed to try to improve the specificity of stool testing for occult blood and to eliminate the need for dietary restrictions recommended for guaiac-based tests. Because human hemoglobin is digested in the stomach and small intestine, fecal immunochemical testing is more selective for colonic bleeding than are the guaiac-based tests.
The fecal immunochemical testing does not require dietary modification for patients and as with the guaiac-based test, is readily available in most clinical settings. These tests do not involve significant risk to the patient. However, just as with the guaiac-based tests, adherence to annual testing is necessary and patients with a positive test need to undergo colonoscopy.
This test employs immunochemical methods to test for blood in the stool. As it detects human globulin, this test is more specific and has low false-positive rates compared to the guaiac-based fecal occult blood test. For the same reason, the fecal immunochemical test does not yield false-negative results in the presence of high-dose vitamin C supplementation and is more specific for lower gastrointestinal bleeding [C].
Stool Deoxyribonucleic Acid Testing (sDNA) Interval Unknown
Cells from the mucosal surface of the colon are shed into the lumen of the colon, and DNA alterations seen in colorectal cancer and in adenomas can be detected using a multitargeted DNA assay. Currently there is only one commercial stool DNA test for colorectal cancer in the U.S.: PreGen-Plus, available through Laboratory Corporation. This test is a second version of the original test; the majority of studies looking at the sensitivity and specificity of stool DNA were done with the first version of the test [C]. The sensitivity for detecting colorectal cancer in these studies was 52% to 91% and the specificity was 93% to 97%. There is currently a single study using the second version of the test that reports a sensitivity of 70% for detecting colorectal cancer [C].
Patients choosing this option for colorectal cancer screening need to be aware that one complete bowel movement is collected and needs to be stored in the refrigerator or frozen until returned to the lab in a collection container supplied by the manufacturer. Stool sample sizes of less than 30 grams are not sufficient and the stool needs to reach the lab within 72 hours of the collection time. This test is currently not Food and Drug Administration (FDA) approved and reimbursement by insurers may be variable. The manufacturer recommends an interval of five years for stool DNA testing, but there is not a consensus regarding the testing interval. Any positive test needs to be evaluated with colonoscopy. It is currently unknown how to manage patients who have a positive stool DNA test but a negative colonoscopy [R].
Neoplastic cells contained in layered DNA are continuously shed into the large bowel lumen. This test employs the detection of such cells in the stool with known DNA alterations leading to carcinogenesis. This test has statistically better sensitivity than the guaiac-based fecal occult blood test [C]. This test is not widely available, and there are still several unanswered questions related to its use: How frequently should the test be repeated after an initial negative one? What is the significance of a positive test, with a negative colonoscopy [R]?