test (Vermillion, Inc., Fremont, CA) is a qualitative serum test that combines
immunoassay results for 5 analytes (CA 125, prealbumin, apolipoprotein A-1,
beta2 microglobulin, and transferrin) into a single numerical score. It
is intended to be used in women with adnexal masses who are planning to have
surgery by a non-gynecologic oncologist for disease considered benign using
routine clinical and radiologic evaluation. In this patient subset, the test
serves as an aid to further assess the likelihood that malignancy is present.
This test will be covered only for this patient subset.
In 2009, it was estimated that more than 21,000 women in the U.S. were diagnosed
with ovarian cancer and more than 14,000 died of this disease (Bristow, 2009).
The mortality rate depends on three variables: 1) characteristics of the
patient; 2) the biology of the tumor (grade, stage and type); and 3) the quality
of treatment (nature of staging, surgery and chemotherapy used) (du Bois, 2009).
In particular, comprehensive staging and completeness of tumor resection
appear to have a positive impact on patient outcome.
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 (Hoskins, 1997). 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) (Tingulstad, 2003). 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 (Giede, 2005).
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 (duBois, 2009). 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) (Goff, 2007).
Optimization of treatment for ovarian cancer may clearly be complicated by these
Adult women presenting with an adnexal mass have an estimated 68% likelihood of
having a benign lesion (Van Holsbeke, 2010). About 6% have borderline tumors,
22% invasive lesions, and 3% metastatic disease.
Obviously a majority of patients can be treated without use of surgical oncology
expertise. To date no existing diagnostic modalities have been identified to
discriminate reliably between benign and malignant lesions. Recent publications
have appeared describing the use of CA 125 with a symptom index (Anderson,
2009), the use of an “ovarian crescent sign” on ultrasound (Van Holsbeke, 2010),
and the use of three-dimensional ultrasound (Alcazar, 2009) to provide increased
diagnostic reliability in this decision-making process, but all of these appear
to require further validation before being considered for routine clinical use.
The OVA1™ is a new proteomic test that has been developed specifically to triage
patients thought to have benign adnexal masses with planned treatment by a
non-gynecologic-oncologist physician. 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
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
not intended to be a screening test or to determine whether a
patient should proceed to surgery. Incorrect use of the OVA1™ test carries the
risk of unnecessary testing, surgery, and/or delayed diagnosis.”