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Detection of genetic abnormalities associated with colorectal cancer (CRC) in stool samples has been proposed as a screening test for CRC. This technology is another potential alternative to currently available screening approaches such as fecal occult blood testing, fecal immunochemical testing (FIT), or colonoscopy.
Several genetic alterations have been associated with colorectal cancer. In the proposed multistep model of carcinogenesis, the tumor suppressor gene p53 and the proto-oncogene K-ras are most frequently altered. Mutations in APC (adenomatous polyposis coli) genes and epigenetic markers (e.g., hypermethylation of specific genes) have also been detected. Colorectal cancer is also associated with DNA replication errors in microsatellite sequences (termed microsatellite instability or MSI) in patients with Lynch syndrome (formerly known as hereditary nonpolyposis colorectal cancer [HNPCC]) and in a subgroup of patients with sporadic colon carcinoma. Tumor-associated gene mutations and epigenetic markers can be detected in exfoliated intestinal cells in stool specimens. Since cancer cells are shed into stool, tests have been developed that detect these genetic alterations in the DNA from shed colorectal cancer cells isolated from stool samples. This has been proposed for use in screening two populations of patients for colon cancer:
1. Known or suspected carriers of Lynch syndrome mutations, considered at high risk of developing colorectal cancer.
In this setting, testing of fecal samples could be used to monitor patients over time for development of colorectal cancer. The test could be used either in lieu of routinely scheduled surveillance colonoscopies or during intervals between scheduled colonoscopies. Those patients testing positive for cancer-related genetic alterations could be further evaluated with colonoscopy.
2. In patients at average risk of colorectal cancer
In this setting, testing of fecal samples could be offered in lieu of, or as an adjunct to, other recommended colorectal cancer screening tests, including fecal occult blood testing, flexible sigmoidoscopy, colonoscopy, or double contrast barium enema.
Several types of tests have been evaluated in studies and some have been marketed. One of these, PreGen-Plus™, tests for 21 different mutations in the p53, APC, and K-ras genes; the BAT-26 MSI marker; and incorporates the DNA Integrity Assay (DIA®). PreGen-Plus™ has not been cleared by the U.S. Food and Drug Administration (FDA). Although the scientific studies that are the basis of the PreGen-Plus™ test were conducted or funded by Exact Sciences, LabCorp is identified as the test developer. LabCorp is regulated under the Clinical Laboratory Improvement Amendments (CLIA) of 1988 and is certified as qualified to perform high-complexity testing. As a result, LabCorp may develop tests in-house and offer them as laboratory services (i.e., laboratory-developed tests). Historically, the FDA has not regulated laboratory-developed tests. However, on January 13, 2006, the FDA sent correspondence to LabCorp indicating that PreGen-Plus™ may be subject to FDA regulation as a medical device. As a consequence, and as a result of studies showing better performance of other tests, this test is no longer offered. On August 12, 2014, Exact Sciences received FDA premarket approval for its latest automated fecal DNA testing product, Cologuard™. Cologuard™ is intended for the qualitative detection of colorectal neoplasia associated DNA markers and for the presence of occult hemoglobin in human stool. A positive result may indicate the presence of CRC or advanced adenoma and should be followed by diagnostic colonoscopy. Cologuard™ is indicated to screen adults of either sex, 50 years or older, who are at average risk for CRC. Cologuard™ is not a replacement for diagnostic colonoscopy or surveillance colonoscopy in high-risk individuals.
Another currently available test is called ColoSure™, developed by OncoMethylome, which detects aberrant methylation of the vimentin (hV) gene. This test is offered as a laboratory-developed test, not subject to FDA regulation.
POLICYDNA analysis of stool samples is considered investigational as a screening technique for colorectal cancer in both patients with average to moderate risk and in patients considered at high risk for colorectal cancer.
POLICY EXCEPTIONSFederal Employee Program (FEP) may dictate that all FDA-approved devices, drugs or biologics may not be considered investigational and thus these devices may be assessed only on the basis of their medical necessity.
Investigative service is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized by certifying boards and/or approving or licensing agencies or published peer review criteria as standard, effective medical practice for the treatment of the condition being treated and as such therefore is not considered medically necessary.
The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.
POLICY HISTORY8/2002: Approved by Medical Policy Advisory Committee (MPAC)
11/5/2003: Code Reference section completed
10/13/2004: Code Reference section updated, CPT code 87999 effective deletion date and note added, ICD-9 diagnosis code 154.0, 197.5, 230.4, V76.41, V76.51 deleted, HCPCS S3890 added
5/2/2006: Policy reviewed, no changes
9/25/2007: Policy reviewed, no changes
04/22/2010: Policy description updated regarding available tests. Policy statement unchanged. FEP verbiage added to the Policy Exceptions section. Deleted outdated references from the Sources section. Deleted CPT code 87999 from the codes table as HCPCS S3890 is the specific code for this test.
02/23/2011: Policy reviewed; no changes
01/17/2012: Policy reviewed; no changes
03/13/2013: Policy reviewed; no changes
03/07/2014: Policy reviewed; no changes
12/31/2014: Added the following new 2015 HCPCS code to the Code Reference section: G0464.
06/15/2015: Policy title changed from "Fecal DNA Testing for Colorectal Cancer Screening and Monitoring" to "Analysis of Human DNA in Stool Samples as a Technique for Colorectal Cancer Screening." Policy description updated regarding tests. Policy statement unchanged.
07/20/2015: Code Reference section updated for ICD-10.
SOURCE(S)Blue Cross Blue Shield Association medical policy #2.04.29
CODE REFERENCEThis may not be a comprehensive list of procedure codes applicable to this policy.