Ovarian cancer is the second most common type of female reproductive cancer but the leading cause of death from gynecological cancer with a 5 year survival rate below 30%. Adult women presenting with an adnexal mass have an estimated 68% likelihood of having a benign lesion, 6% have borderline tumors, 22% invasive lesions, and 3% metastatic disease. The need for proper triage and specialty care is warranted to improve survival and health outcomes. According to ACOG, “It has been well-established that women with ovarian cancer whose care is managed by a physician who has advanced training and expertise in the treatment of women with gynecologic cancer, such as a gynecologic oncologist, have improved overall survival rates as compared with those treated without such collaboration.”
A variety of proteomic biomarkers have been studied in association with ovarian cancer. Of particular interest are tests that develop a risk score based on the results of multiple analytes. They have been investigated for use in women with adnexal masses of unknown origin, based on routine clinical and radiological evaluations. The scores can be used to estimate the probability of an underlying malignant process and may be useful in determining the pre-operative plan of care.
Several of these tests (e.g. Overa®, OVA1® and ROMA®) have been designated as Class II devices by the FDA. They are quantitative serum tests that employ specific algorithms to ascribe the risk score.
Proteomics-based testing (e.g., Overa®, OVA1® and ROMA®) for all uses, including but not limited to the following, is considered investigational:
preoperative evaluation of adnexal masses to assess for malignancy
screening for ovarian cancer
selecting patients for surgery for an adnexal mass
evaluation of patients with clinical or radiologic evidence of malignancy
evaluation of patients with nonspecific signs or symptoms suggesting possible malignancy
postoperative testing and monitoring to assess surgical outcome and/or to detect recurrent malignant disease following treatment
Any specific products referenced in this policy are just examples and are intended for illustrative purposes only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available. These examples are contained in the parenthetical e.g. statement.
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.
The 2009 submission of the OVA1® to the FDA carried the precautionary statement that it is not intended to be used as a screening test or to determine whether a patient should proceed to surgery. The evidence for use of proteomics-based testing (Overa®, OVA1® test or ROMA® test) is insufficient to determine the effects of the technology on health outcomes.
American College of Obstetricians and Gynecologists. (2016). Evaluation and management of adnexal masses. Practice Bulletin 174. Retrieved August 7, 2017 from The American College of Obstetricians and Gynecologists.
BlueCross BlueShield Association. Medical Policy Reference Manual. (12:2017). Multimarker serum testing related to ovarian cancer (2.04.62). Retrieved July 31, 2018 from BlueWeb. (30 articles and/or guidelines reviewed)
Bristow, R. E., Smith, A., Zhang, Z., Chan, D. W., Crutcher, G., & Fung, E. T. (2013). Ovarian malignancy risk stratification of the adnexal mass using a multivariate index assay. Gynecologic Oncology, 128, 252-259. (Level 2 evidence)
Coleman, R. L., Herzog, T. J., Chan, D. W., Munroe, D. G., Pappas, T. C., Smith, A., et al. (2016). Validation of a second-generation multivariate index assay for malignancy risk of adnexal masses. American Journal of Obstetrics & Gynecology, 215 (1), 82.e1-82.e11. Abstract retrieved September 30, 2016 from PubMed database.
Dayyani, F., Uhlig, S., Colson, B., Simon, K., Rolny, V., Morgensterm, D., et al. (2016, November) Diagnostic performance of risk of ovarian malignancy algorithm against CA 125 and HE4 in connection with ovarian cancer: a meta-analysis. International Journal of Gynecologic Cancer, 26 (9), 1586-1593. Abstract retrieved August 7, 2017 from PubMed database.
Goodrich, S. T., Bristow, R. E., Santoso, J. T., Miller, R. W., Smith, A., Zhang, Z., et al. (2014). The effect of ovarian imaging on the clinical interpretation of a multivariate index assay. American Journal of Obstetrics & Gynecology, 2014, 210. (Level 2 evidence)
Grenache, D., Heichman, K., Werner, T., & Vucetic, Z. (2015). Clinical performance of two multi-marker blood tests for predicting malignancy in women with an adnexal mass. Clinica Chimica Acta, 438, 358-363. Abstract retrieved August 7, 2017 from PubMed database.
Longoria, T. C., Ueland, F. R., Zhang, Z., Chan, D. W., Smith A., Fung, E. T. Clinical performance of a multivariate index assay for detecting early-stage ovarian cancer. American Journal of Obstetrics & Gynecology, 2013, 209, 1e1-1e9. (Level 3 evidence)
National Comprehensive Cancer Network. (2018, March). NCCN clinical practice guidelines in oncology (NCCN guideline®). Ovarian cancer including fallopian tube cancer and primary peritoneal cancer, V.2.2018. Retrieved July 31, 2018 from www.nccn.com.
National Institute of Health and Clinical Excellence. (2011). Ovarian cancer. Retrieved January 2, 2013 from http://www.nice.org.
Simmons, A., Clarke, C., Badgwell, D., Lu, Z., Sokoll, L., Lu, K., et al. (2016, July), Validation of a biomarker panel and longitudinal biomarker performance for early detection of cancer. International Journal of Gynecologic Cancer, 26 (6), 1070-1077. (Level 4 evidence)
Technology Evaluation Center. (2013, April). Multianalyte testing for the evaluation of adnexal masses. (Volume 27, No. 8). Retrieved June 9, 2014 from http://www.bcbs.com. (29 articles and/or guidelines reviewed)
U.S. Food and Drug Administration. (2009, September). Center for Devices and Radiological Health. 510(k) Premarket Notification Database. K081754 (Ova1®). Retrieved September 25, 2012 from http://www.accessdata.fda.gov.
U.S. Food and Drug Administration. (2011, September). Center for Devices and Radiological Health. 510(k) Premarket Notification Database. K103358 (ROMA®). Retrieved September 25, 2012 from http://www.accessdata.fda.gov.
U.S. Food and Drug Administration. (2016, March). Center for Devices and Radiological Health. 510(k) Premarket Notification Database. K150588 (Overa®). Retrieved August 7, 2017 from http://www.accessdata.fda.gov.
Winifred S. Hayes, Inc. Medical Technology Directory. (2012, December; archived January 2018). Architect HE4 assay for ovarian cancer detection. Retrieved July 31, 2018 from www.hayesinc.com. (48 articles and/or guidelines reviewed)
ORIGINAL EFFECTIVE DATE: 5/14/2011
MOST RECENT REVIEW DATE: 9/13/2018
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