DESCRIPTION
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 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, a test has been developed that detects 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 individuals for colon cancer:
Known or suspected carriers of HNPCC 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 routines scheduled surveillance colonoscopies or during intervals between scheduled colonoscopies. Those patients testing positive for cancer-related genetic alterations could be further evaluated with colonoscopy.
In patients at average risk of colorectal cancer - In this setting, testing of fecal samples could be offered in lieu of, or in 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.
The 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.
POLICY
DNA analysis of stool samples as a screening technique for colorectal cancer in both individuals with average to moderate risk, and in individuals at high risk for colorectal cancer, is considered investigational.
IMPORTANT REMINDER
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
ADDITIONAL INFORMATION
Well-designed, randomized, controlled trials with long-term follow-up are not available to determine long-term benefits of analysis of human DNA in stool samples as a technique for colorectal cancer screening compared to alternative treatments.
SOURCES
BlueCross BlueShield Association. Medical Policy Reference Manual. (5:2007). Analysis of human DNA in stool samples as a technique for colorectal cancer screening (2.04.29). Retrieved July 23, 2008 from BlueWeb.
Complete Guide to Medicare Coverage Issues [Computer software]. (2010, April). Colorectal cancer screening tests. (NDC 210.3, p. 2-161 – 2-163). Ingenix.
Levin, B., Lieberman, D. A., McFarland, B., Smith, R. A., Brooks, D., Andrews, K. S., et al. (2008). 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 Journal for Clinicians, 58 (3), 130-160.
Technology Evaluation Center. (2006, August). Special report: fecal DNA analysis for colon cancer screening. (Vol.21, No. 6). Retrieved July 23, 2008 from: http://www.bcbs.com/blueresources/tec/vols/21/21_06.pdf. (69 articles and/or guidelines reviewed)
ORIGINAL EFFECTIVE DATE: 3/1/2003
MOST RECENT REVIEW DATE: 5/12/2011
ID_BA
Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.
This document has been classified as public information.