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DESCRIPTIONThere are a variety of gene-based biomarkers that 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 have now been cleared by FDA for use in women with adnexal masses (Ova1™ test and ROMA™ test) as an aid to further assess the likelihood that malignancy is present.
In 2009, it was estimated that more than 21,000 women in the US were diagnosed with ovarian cancer and more than 14,000 died of this disease. The mortality rate depends on three variables:
In 1997, the Society of Surgical Oncology first recommended ovarian cancer surgery and follow-up treatment be performed by physicians with ovarian cancer disease expertise. To date dozens of articles and several meta-analyses or systemic reviews have been published relevant to this recommendation looking at long-term outcomes, short-term outcomes and process measures (types of treatment such as complete staging or tumor debulking).
At least two meta-analyses have been performed concluding improved outcomes in patients with ovarian cancer when treated by gynecologic oncologists. Data is most convincing for patients with advanced stage disease. Median improvements in survival for patients treated by non-gynecologic oncologists versus gynecologic oncologists have been variable but impressive with increases recently reported to be up to 8 months (12 to 21 months). In at least some reports, important differences have also been observed showing improved survival in patients with early stage disease as well when treated by gynecologic oncologists.
A recent systematic review of 198 studies addressing the role of specialty treatment by gynecologic oncologists and evaluation of other practice related factors (type of hospital, surgical volume, etc.) was more guarded in its analysis. This review noted that not all reports confirmed these findings of improved performance based on sub-specialty. It also noted that in some reports only patients presenting with certain stages of disease (in most cases advanced stage although in some cases early stage) were studied and found to exhibit treatment differences. Nevertheless, this review also concluded that the use of sub-specialists and better education of treatment options for both primary care physicians and patients was warranted.
In an analysis of predictors of comprehensive surgical treatment (meticulous and extensive disease staging, efforts at debulking of the tumor with removal of all visible lesions, lymphadenectomy) in patients with ovarian cancer, Goff et al. observed that comprehensive treatment was linked not only to physician factors but also to a number of simple demographic factors including age, race, insurance status and geographic location (urban versus rural). Optimization of treatment for ovarian cancer may clearly be complicated by these factors.
Adult women presenting with an adnexal mass have an estimated 68% likelihood of having a benign lesion. About 6% have borderline tumors, 22% invasive lesions, and 3% metastatic disease.
A majority of patients can be treated without use of surgical oncology expertise. Referral guidelines have been published by the American College of Obstetricians and Gynecologists (ACOG) and the Society of Gynecologic Oncologists (SGO) for women with pelvic masses that are suspicious for ovarian cancer who are being referred to gynecologic oncologists. (10) In these guidelines, a decision to refer in postmenopausal women was based on the presence of at least one of the following indicators: elevated CA 125, ascites, a nodular or fixed pelvic mass, evidence of abdominal or distant metastasis, or a family history of one or more first-degree relatives with ovarian or breast cancer. A decision to refer in premenopausal women was based on at least one of the following: elevated CA 125, ascites, evidence of abdominal or distant metastasis, or a positive family history.
A validation study has been performed on these criteria, suggesting a high negative predictive value ([NPV] 90% or more) in both premenopausal and postmenopausal patients but a much lower positive predictive value (PPV, as low as 34%).
Recent publications have appeared describing the use of CA 125 with a symptom index, the use of an “ovarian crescent sign” on ultrasound, the use of 3-dimensional ultrasound to provide increased diagnostic reliability in this decision-making process, and most recently the use of an algorithm based on use of key features identified by ACOG/SGO. Since many of these studies have been performed in referral centers, it is not clear how generalizable they are to use in the general population. Further independent validation of these various approaches is needed.
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 should be considered candidates for referral to a gynecologic oncologist for treatment. As described above, this treatment is likely to produce improved patient outcomes.
On July 16, 2009, the Vermillion OVA1 test was cleared for market by the FDA as a 510(k) submission. No predicate was identified and the review decision was based on the de novo (automatic classification of class III devices) 510(k) review process. The intended use carried a boxed warning: “PRECAUTION: The OVA1TM test should not be used without an independent clinical/radiological evaluation and is not intended to be a screening test or to determine whether a patient should proceed to surgery. Incorrect use of the OVA1TM test carries the risk of unnecessary testing, surgery, and/or delayed diagnosis.”
On September 1, 2011, the Risk of Ovarian Malignancy Algorithm (ROMA™ test, Fujirebio Diagnostics, Inc., Malvern, PA) was cleared by the U.S. Food and Drug Administration (FDA) as a 510(k) submission. 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.
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 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 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.
SOURCE(S)Blue Cross Blue Shield Association policy # 2.04.62
This is not an all-inclusive list of non-covered procedure codes.
All codes billed for this procedure are considered investigational and not eligible for coverage.