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A variety of gene-based biomarkers have been studied in association with ovarian cancer. Of particular interest have been tests that integrate results from multiple analytes into a risk score to predict the presence of disease. Two tests based on this principle (OVA1™ test, ROMA™ test) have been cleared by FDA for use in women with adnexal masses as an aid to further assess the likelihood that malignancy is present.
More than 21,000 women in the U.S. are diagnosed each year with ovarian cancer and approximately 14,000 died of this disease. The mortality rate depends on three variables:
In 1997, the Society of Surgical Oncology recommended ovarian cancer surgery and follow-up treatment be performed by physicians with ovarian cancer disease expertise. To date, dozens of articles have been published on the application of this recommendation looking at long-term outcomes, short-term outcomes, and process measures (eg, types of treatment such as complete staging or tumor debulking). At least two meta-analyses have concluded that outcomes are better in patients with ovarian cancer when they are treated by gynecologic oncologists. Data have been most convincing for patients with advanced-stage disease.
Adult women presenting with an adnexal mass have an estimated 68% likelihood of having a benign lesion. About 6% have borderline tumors, 22%, invasive malignant lesions, and 3% metastatic disease. Clinicians generally agree that women with masses that have a high likelihood of malignancy should undergo surgical staging by gynecologic oncologists. However, women with clearly benign masses do not require referral to a specialist. Criteria and tests that help differentiate benign from malignant pelvic masses are thus desirable.
In 2005, the American College of Obstetricians and Gynecologists and the Society of Gynecologic Oncologists jointly released referral guidelines that address criteria for referring women with pelvic masses that are suspicious for ovarian cancer to gynecologic oncologists. Separate criteria were developed for premenopausal and postmenopausal women. In premenopausal women, referral criteria included at least one of the following: elevated CA125 (>200 U/mL), ascites, evidence of abdominal or distant metastasis, or a positive family history. The referral criteria in postmenopausal women were similar, except that a lower threshold for an elevated CA125 test was used (35 U/mL) and nodular or fixed pelvic mass was an additional criterion.
Two proteomic tests have now been cleared by the U.S. Food and Drug Administration (FDA) with the intended use to triage patients with adnexal masses. A suggested use of the test is to identify women with a positive test who have a higher likelihood of malignant disease and may benefit from referral to a gynecologic-oncology specialist. Patients with positive results may be considered candidates for referral to a gynecologic oncologist for treatment. The tests have been developed and evaluated only in patients with adnexal masses who are going on to have surgical removal. Other potential uses, such as selecting patients to have surgery, screening asymptomatic patients, and monitoring treatment have not been investigated. Furthermore, the tests are not intended to be used as stand-alone tests, but are intended to be used in conjunction with clinical assessment.
On July 16, 2009, the OVA1™ test (Vermillion Inc. Fremont, CA) was cleared for marketing by the FDA as a 510(k) process. On September 1, 2011, the Risk of Ovarian Malignancy Algorithm (ROMA™ test, Fujirebio Diagnostics, Malvern, PA) was cleared for marketing by the U.S. Food and Drug Administration (FDA) through the 510(k) process. Because the OVA1 test had been found to be a class II medical device by virtue of the July 2009 clearance, ROMA was found to be substantially equivalent to that predicate device. Intended use of OVA1 is as an aid to further assess the likelihood that malignancy is present when the physician’s independent clinical and radiological evaluation does not indicate malignancy. Intended use of ROMA is as an aid, in conjunction with clinical assessment, in assessing whether a premenopausal or postmenopausal woman who presents with an ovarian adnexal mass is at high or low likelihood of finding malignancy on surgery. Neither test is FDA-cleared as a screening or stand-alone diagnostic assay.
Black Box Warning
For additional information regarding proteomic tests for other cancers, refer to the Analysis of Proteomic Patterns in Serum to Identify Cancer medical policy.
POLICYAll uses of the OVA1 and ROMA tests are investigational, including but not limited to:
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.
POLICY GUIDELINESInvestigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.
The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.
POLICY HISTORY07/22/2010: Approved by Medical Policy Advisory Committee
06/21/2011: Policy reviewed; no changes.
02/20/2013: Policy description updated to add information regarding the ROMA test. Policy statement revised to delete the following medically necessary policy statement: The proteomics-based OVA1TM test may be considered medically necessary as an aid to further assess the likelihood that malignancy is present when the physician’s (other than gynecological oncologist) independent clinical and radiological pre-operative evaluations do not indicate malignancy in a patient with an ovarian (adnexal) mass. This testing is now considered investigational for all indications. The Code Reference section changed from Covered to Non-Covered. Added CPT codes 81500 and 81503 to the Code Reference section as non-covered. Deleted 84999, 220, 236.2, 239.5, and 620.2 from the Code Reference section.
03/25/2014: Policy title changed from "Proteomics-based Testing for the Evaluation of Ovarian (Adnexal) Masses" to "Proteomics-Based Testing Related to Ovarian Cancer." No changes to policy statement.
01/09/2015: Policy description revised and updated regarding devices. Policy statement unchanged.
08/14/2015: Code Reference section updated for ICD-10.
12/21/2015: Policy description updated regarding proteomic tests. Policy statement unchanged. Investigative definition updated in policy guidelines section.
SOURCE(S)Blue Cross Blue Shield Association policy # 2.04.62
CODE REFERENCEThis may not be a comprehensive list of procedure codes applicable to this policy.