|MP 2.01.66||Immunochemical Fecal Occult Blood Testing (Archived)|
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Our medical policies are designed for informational purposes only and are not an authorization, or an explanation of benefits, or a contract. Receipt of benefits is subject to satisfaction of all terms and conditions of the coverage. Medical technology is constantly changing, and we reserve the right to review and update our policies periodically.
Immunochemical fecal occult blood tests (iFOBT) are proposed for colorectal cancer screening as an alternative to guaiac-based FOBT. iFOBT does not have dietary or drug restrictions prior to sample collection, and possibly simpler sampling instructions, which may lead to higher patient compliance.
Colorectal cancers and some precancerous adenomas often bleed periodically. Consequently, small amounts of blood in the stool (fecal occult blood) in the absence of other explanatory conditions is a marker for neoplasia. Immunochemical fecal occult blood tests (iFOBT) are used for colorectal cancer screening by employing antibodies to detect the globin portion of human hemoglobin in stool. Because globin is degraded during passage through the upper GI tract, the iFOBT is specific for bleeding that is limited to the colon and rectum.
The primary risk factor for colorectal cancer is age; more than 90% of cases are diagnosed in adults over age 50. It is estimated that at age 50 a person has about a 5% remaining lifetime risk of being diagnosed with colorectal cancer. About 20% of cases occur in persons with specific risk factors (e.g., inflammatory bowel disease), and about 6% arise from persons with uncommon genetic syndromes such as familial adenomatous polyposis. The incidence also is increased in individuals with a personal or family history of colorectal cancer or polyps.
Colorectal cancer in the early stages is largely asymptomatic and frequently cured by surgery alone. Survival rates are much better when diagnosed and treated at an early stage. Thus, annual screening for early colorectal cancer is recommended beginning at age 50 for those with no risk factors other than age. Guaiac fecal occult blood testing (gFOBT) has been the standard test used for screening but requires complicated dietary and drug restrictions prior to testing and sampling instructions may limit patient compliance. iFOBTs offer testing without dietary or drug restrictions and may offer simpler sampling instructions.
A number of iFOBTs have been approved by the U.S. Food and Drug Administration (FDA) for marketing in the U.S. These are InSure™ (Enterix, Inc.), Instant-View® (Alpha Scientific Designs, Inc.), immoCARE (Care Products, Inc.), and MonoHaem® (Chemicon International, Inc.). The tests require sample collection from 1 (Instant-View®, immoCARE), 2 (InSure™), or 3 stools (MonoHaem®). The test formats for several iFOBTs require minimal processing and involve developing a test strip with controls and reading a color reaction. In the case of the InSure™ iFOBT, all tests are developed by Quest Diagnostic Laboratories through an exclusive arrangement. For InSure™, a dry stool specimen is not required and the sample may be collected by brushing the surface of the stool while in the toilet bowl water, which may be more agreeable to the patient.Review of the FDA website indicated that a number of additional iFOBTs have been cleared through the 510(k) process. Some (not the entire list) of these include Hema-Screen Specific (Immunostics), Innovacon Flipcard Fecal Occult Blood Test (Innovacon), OC Auto Micro FOB Test (Polymedco and Eiken), FlexSure OBT (SmithKline Diagnostics), Teco Rapid FOB Card Test (TECO Diagnostics), and inSure II (Enterix, Inc.). In addition, the iScreen FOB is noted to be cleared by FDA and waived under Clinical Laboratory Improvement Amendments (CLIA), and thus available for point-of-care testing.
Immunochemical fecal occult blood testing is considered medically necessary for colorectal cancer screening.
The iFOBTs approved for marketing in the United States are categorized as waived under Clinical Laboratory Improvement Amendments of 1988 (CLIA) regulation and may be developed in any laboratory, such as a physician’s office lab, with a CLIA license for waived tests. Tests may be waived from regulatory oversight if they meet certain requirements established by the statute. Minimal scientific and technical knowledge, training, and experience are required to perform waived tests.
BlueCard/National Account Issues
Specific contractual exclusions for screening tests may affect coverage eligibility for iFOBT as a screening test for colorectal cancer.
The InSure™ iFOBT, is developed by Quest Diagnostic Laboratories through an exclusive arrangement and may require out-of-network processing.
A 2004 TEC Assessment found no reported prospective, controlled trials of iFOBT screening and colorectal cancer incidence or mortality outcomes and concluded that the evidence is insufficient for drawing conclusions on the clinical performance of iFOBTs. (1)
At this time, there are no randomized clinical trials of iFOBT for the prevention of colon cancer mortality. However a large body of indirect evidence has been published and it has been reviewed in recent guideline documents from the U.S. Preventive Services Task Force (USPSTF) and the joint guideline from the American Cancer Society and U.S. Multi-Society Task force on Colorectal Cancer. (2, 3) Most of these studies compare various types of FOBTs in comparison to a reference standard of colonoscopy or sigmoidoscopy along with clinical follow-up for a single episode of screening. Measures of sensitivity and specificity can be calculated from these types of studies, but it is difficult to ascertain the effectiveness of an overall screening program which would consist of annual or other time interval screening.
The recommendation of the U.S. Preventive Services Task force regarding iFOBT appears to be an endorsement of iFOBT. The clinical summary section of the document states that high-sensitivity FOBT receives a Grade A recommendation. iFOBT is not specifically mentioned in the guideline statement. However, in the accompanying systematic review, the abstract states that four fecal immunochemical tests “have superior sensitivity… and some have similar specificity... to the Hemoccult II fecal occult blood test….” (4) Later in the abstract it states that “Fecal tests with better sensitivity and similar specificity are reasonable substitutes for traditional fecal occult blood test.” However, it appears that the traditional (non-high sensitivity) fecal occult blood test is not recommended. In a qualitative ranking of the various tests, iFOBT was considered less than or equal in sensitivity than Hemoccult SENSA (a high-sensitivity guaiac-based FOBT) and more specific.
The American Cancer Society/Multi-Society Task Force reviewed 6 studies that compared different iFOBT with Hemoccult SENSA, since SENSA has the highest sensitivity of currently marketed guaiac-based FOBT. (3) Their overall conclusion was that there was no clear pattern of superior performance in overall test characteristics between the two tests. Their joint guideline contains an unambiguous endorsement of iFOBT, along with endorsements of high-sensitivity guaiac-based FOBT and stool DNA tests. (3)
The U.S. Preventive Services Task Force systematic review found 9 fair- or good-quality cohort studies evaluating iFOBT in over 86,000 persons. (4) This review tends to compare various iFOBT to traditional guaiac-based (non-high sensitive) FOBT. Overall iFOBT’s had higher sensitivity for colorectal cancer (61% to 91%) than had been reported for Hemoccult II (25% to 38%) in another systematic review. Estimated specificity varied across types of tests, from 91% to 98%, which was lower than the specificity of Hemoccult II. They note that the different iFOBT tests cannot be clearly analyzed as a class. Several of the studies reviewed were of tests that are not marketed in the U.S.
A study by Allison (included in the ACS and USPSTF reviews) of the FlexSure OBT, which is available and marketed in the U.S., showed a sensitivity of 82% and specificity of 97% for left-sided (i.e., detectable by sigmoidoscopy) colorectal cancer, which was better for both characteristics than Hemoccult Sensa (64% and 90%, respectively), a high-sensitivity test, in the same patients. (5) However, sensitivity of the iFOBT was worse for large adenomas (29.5% versus 41.3%), although specificity was better. In this study, predictive values and likelihood ratios were better for FlexSure; but as noted elsewehere, these performance characteristics cannot be assumed for all iFOBTs. (The USPSTF report noted that estimated specificity varied (91% to 98%) across fecal immunochemical tests.) The study by Allison also reported higher sensitivities than some other studies, which the authors felt was due at least in part to collecting three specimens, instead of one.
In summary, based on published studies and recommendations from national organizations such as the USPSTF, iFOBT may be considered medically necessary in screening for colorectal cancer.
The policy was updated with a literature search based on the MEDLINE database for the period January 2009 through January 2010.
There continue to be studies comparing different iFOBT. Hundt and colleagues conducted a prospective multicenter screening study in Germany that evaluated the performance of 6 iFOBT and a guiaic-based FOBT. (6) The iFOBT evaluated were Bionexia FOBplus (DIMA, Germany), Bionexia Hb/Hp Complex (DIMA, Germany), PreventID CC (Preventis, Germany), ImmoCARE-C (CAREdiagnostica Germany), FOB advanced (Ultimed, Germany) and QuickVue iFOB (Quidel, San Diego, CA). Only the QuickVue test has been approved by the FDA. The study included average-risk individuals (i.e., no inflammatory bowel disease, visible rectal bleeding or other conditions indicating possible increased risk) who returned stool samples by the date of their colonoscopy appointment. Colonoscopy served as the gold standard test; these were conducted by physicians blinded to FOBT results. A total of 1319 patients met eligibility criteria and were included in the analysis; 405 (30.7%) had a positive colonoscopy result (detection of any adenoma). An advanced adenoma was detected in 130 (10%) of participants. There was a wide range in the sensitivities and specificities of the iFOBT. Sensitivity for the detection of any adenoma ranged from 11.4% (95% confidence interval [CI] = 8.4-14.9%) for ImmoCARE-C to 58.0% (95% CI =53.1-62.9%) for Bionexia Hb/Hp Complex. Sensitivity for the detection of advanced adenomas (the authors did not define what they meant by advanced) ranged from 25.4% (95% CI =18.2-33.8%) for ImmoCARE-C to 71.5% (95% CI =63.0-79.1%) for Bionexia Hb/Hp Complex. Specificities ranged from 58.5% to 96.7%; only 2 tests (ImmunoCareC and FOB advanced) had specificities above 90%. QuickVue, a test cleared by the U.S. FDA, had a sensitivity of 45.2 (95% CI =40.3-50.2%) for detecting any adenoma and 56.2 (95% CI =47.2-64.8%) for detecting an advanced adenoma and a specificity of 70.2% (95% CI =67.2%-83.2%). The guiaic-based test had a lower sensitivity than any of the iFOBT e.g., 5.4% (95% CI =3.4-5.8%) for any adenoma and a specificity of 95.9% (95% CI =94.4-97.1%) which was higher than all but one of the iFOBT.
Results of the new study identified for this update support the findings of previous studies that iFOBT generally have high sensitivities and that there are large differences in the diagnostic performance of iFOBT. Thus, the policy statement remains unchanged; iFOBT may be considered medically necessary for colorectal cancer screening.
Technology Assessments, Guidelines and Position Statements
U.S. Preventive Services Task Force: In October 2008, issued a Grade A recommendation, “The USPSTF recommends screening for colorectal cancer (CRC) using fecal occult blood testing, sigmoidoscopy, or colonoscopy, in adults, beginning at age 50 years and continuing until age 75 years. The risks and benefits of these screening methods vary.” (2)
American Cancer Society/ US Multi-Society Task Force on Colorectal Cancer/ American College of Radiology: In May/June, 2008, published a guideline that included, as options for colorectal cancer screening, guaiac FOBT with high sensitivity for cancer (annual), immunochemical FOBT with high sensitivity for cancer (annual) or a stool DNA test with high sensitivity for cancer (interval unknown). (3)
American College of Gastroenterology: In 2009, updated guidelines on colorectal cancer screening were published. The guidelines included the statement that the preferred strategy is colonoscopy since this is a prevention test as well as a cancer detection test. When colonoscopy is not possible, or when a patient declines colonoscopy, the preferred cancer detection test is annual iFOBT. (7)
Medicare National Coverage
Effective January 1, 2004, there was Medicare coverage for screening for early detection of colorectal cancer by using immunochemical FOBT as an alternative to guiaic-based FOBT. Medicare coverage continued to allow one FOBT per year for beneficiaries aged 50 and over.
- 2004 TEC Assessments; Tab 5.
- U.S. Preventive Services Task Force. Screening for colorectal cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2008; 149(9):627-637.
- Levin B, Lieberman DA, McFarland B et al. Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. CA Cancer J Clin 2008; 58(3):130-60. Accessible online at: http://caonline.amcancersoc.org/cgi/reprint/58/3/130.
- Whitlock EP, Lin JS, Liles E et al. Screening for colorectal cancer: a targeted, updated systematic review for the US Preventive Services Task Force. Ann Intern Med 2008; 149(9):638-58.
- Allison JE, Sakoda LC, Levin TR et al. Screening for colorectal neoplasms with new fecal occult blood tests: update on performance characteristics. J Natl Cancer Inst 2007; 99(19):1462-70. Accessible online at: http://jnci.oxfordjournals.org/cgi/reprint/99/19/1462.
- Hundt S, Haug U, Brenner H et al. Comparative evaluation of immunochemical fecal occult blood tests for colorectal adenoma detection. Ann Intern Med 2009; 150(3):162-9.
- Rex DK, Johnson D, Anderson JC et al. American College of Gastroenterology guidelines for colorectal cancer screening 2008. Am J Gastroenterol 2009; 104(3):739-50.
|Blood, occult, by fecal hemoglobin determination by immunoassay, qualitative, feces, 1-3 simultaneous determinations|
|82270||Blood, occult, by peroxidase activity(eg, guaiac), qualitative, feces, consecutive collected specimens with single determination, for colorectal neoplasm screening (ie, patient was provided three cards or single triple card for consecutive collection)|
|ICD-9 Diagnosis||V76.51||Screening for malignant neoplasm of colon or colorectal|
|154.0||Malignant neoplasm, colon with rectum|
|HCPCS||G0328||Colorectal cancer screening; fecal-occult blood test, 1-3 immunoassay, 1-3 simultaneous determinations|
|Type of Service||Pathology/Laboratory|
|Place of Service||Laboratory/Physician’s office|
Immunochemical Fecal Occult Blood Testing
Fecal Occult Blood Testing, Immunochemical
|07/15/04||Add to Medicine section||New policy|
|05/23/05||Replace policy||Policy updated with literature search; no changes in policy statement|
|07/20/06||Replace policy||Policy updated with literature search; added a sentence to the Rationale section on the ACS position on fecal occult blood testing. No changes in policy statement|
|10/13/06||Policy revision||Policy updated, allowed in lieu of 82274|
|1/08/09||Replace policy||Policy updated with literature review and revised extensively. Reference list revised extensively. Policy statement changed to indicate testing may be considered medically necessary.|
|03/11/10||Replace policy -ARCHIVED||Policy updated with literature search; no change in policy statement. Reference numbers 6 and 7 added. Policy archived.|