MEDICAL POLICY

POLICY
RELATED POLICIES
POLICY GUIDELINES
DESCRIPTION
SCOPE
BENEFIT APPLICATION
RATIONALE
REFERENCES
CODING
APPENDIX
HISTORY

Proteomics-Based Testing Related to Ovarian Cancer

Number 2.04.62

Effective Date December 27, 2013

Revision Date(s) 12/09/13; 12/11/12

Replaces N/A

Policy

All uses of the OVA1 and ROMA tests are investigational, including but not limited to

  • Preoperative evaluation of adnexal masses to triage for malignancy, or
  • Screening for ovarian cancer, or
  • Selecting patients for surgery for an adnexal mass, or
  • Evaluation of patients with clinical or radiologic evidence of malignancy, or
  • Evaluation of patients with nonspecific signs or symptoms suggesting possible malignancy, or
  • Postoperative testing and monitoring to assess surgical outcome and/or to detect recurrent malignant disease following treatment.

Related Policies

2.03.501

Serum Tumor Markers

12.04.66

Serum Biomarker Human Epididymis Protein 4 (HE4)

Policy Guidelines

OVA1 and ROMA tests are combinations of several separate lab tests and involve a proprietary algorithm for determining risk (i.e., they are what the American Medical Association’s CPT calls “Multianalyte Assays with Algorithmic Analyses” [MAAAs]).

Coding

CPT

81500

Oncology (ovarian), biochemical assays of two proteins (CA-125 and HE4), utilizing serum, with menopausal status, algorithm reported as a risk score – is specific to the ROMA test

81503

Oncology (ovarian), biochemical assays of five proteins (CA-125, apoliproprotein A1, beta-2 microglobulin, transferrin and pre-albumin), utilizing serum, algorithm reported as a risk score – is specific to OVA1

CPT instructs that these codes cannot be reported with the component tests (i.e., codes 86304 and 86305 cannot be reported with 81500, and codes 82172, 82232, 83695, 83700, 84134, 84466, and 86304 cannot be reported with 81503).

Description

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 and ROMA™ test) have now been cleared by FDA for use in women with adnexal masses as an aid to further assess the likelihood that malignancy is present.

Background

In 2009, more than 21,000 women in the U.S. were diagnosed with ovarian cancer and more than 14,000 died of this disease. (1) 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). (2) 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 recommended ovarian cancer surgery and follow-up treatment be performed by physicians with ovarian cancer disease expertise. (3) To date, dozens of articles have been published relevant to this recommendation looking at long-term outcomes, short-term outcomes, and process measures (e.g. 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. (4, 5) 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. (6) 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 (ACOG) and the Society of Gynecologic Oncologists (SGO) jointly released referral guidelines that address criteria for referring women with pelvic masses that are suspicious for ovarian cancer to gynecologic oncologists. (7) Separate criteria were developed for pre-menopausal and post-menopausal women. In premenopausal women, referral criteria included at least one of the following: elevated CA 125 (greater than 200 unites per 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 CA-125 test was used (35 units per 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.

Regulatory Status

On July 16, 2009, the OVA1TM test (Vermillion, Inc. Fremont, CA) was cleared for market by the U.S. Food and Drug Administration (FDA) as a 510(k) submission. On September 1, 2011, the Risk of Ovarian Malignancy Algorithm (ROMATM 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.

Black Box Warning: On December 10, 2011, the FDA published an amendment to the regulation for classifying ovarian adnexal mass assessment score test systems to restrict these devices so that a prescribed warning statement that addresses off-label risks be highlighted by a black box warning. (8) The warning is intended to mitigate the risk to health associated with off-label use as a screening test, stand-alone diagnostic test, or as a test to determine whether or not to proceed with surgery.

Scope

Medical policies are systematically developed guidelines that serve as a resource for Company staff when determining coverage for specific medical procedures, drugs or devices. Coverage for medical services is subject to the limits and conditions of the member benefit plan. Members and their providers should consult the member benefit booklet or contact a customer service representative to determine whether there are any benefit limitations applicable to this service or supply.

Benefit Application

N/A

Rationale

Literature Review

This policy was originally created in 2010 and was updated regularly with searches of the MEDLINE database. The most recent literature search was performed for the period October 2012 through September 30, 2013. The literature review focuses on the following three issues related to evaluation of diagnostic tests:

Assessment of a diagnostic technology typically focuses on 3 parameters: 1) technical performance; 2) diagnostic performance (sensitivity, specificity, and positive [PPV] and negative predictive value [NPV]) in appropriate populations of patients; and 3) demonstration that the diagnostic information can be used to improve patient outcomes (clinical utility).

Technical performance: This is typically assessed with 2 types of studies, those that compare test measurements with a gold standard and those that compare results taken with the same device on different occasions (test-retest).

Diagnostic performance: This is evaluated by the ability of a test to accurately diagnose a clinical condition in comparison with the gold standard. The sensitivity of a test is the ability to detect a disease when the condition is present (true -positive), while specificity indicates the ability to detect patients who are suspected of disease but who do not have the condition (true -negative). Evaluation of diagnostic performance, therefore, requires independent assessment by the 2 methods in a population of patients who are suspected of disease but who do not all have the disease.

Clinical Utility

This involves assessing the data linking use of a test to improvement in patient management and/or health outcomes. While in some cases, tests can be evaluated adequately using technical and diagnostic performance. when a test identifies a new or different group of patients with a disease; randomized trials are needed to demonstrate impact of the test on the net health outcome.

Technical Performance

Descriptions of the developmental process for the OVA1 test have been published in FDA documents and in a perspective by Fung in 2010. (9-11) candidate biomarkers were selected based on initial studies using mass spectroscopy but were converted to standard immunoassays to improve analytical performance. Seven final markers were evaluated, none of which individually appeared to be highly specific for malignant ovarian disease. However, the choice of 5 of these (CA 125, prealbumin, apolipoprotein A-1, beta 2 microglobulin, and transferrin) produced a composite profile that did appear to have discriminatory ability. The test, as cleared by FDA, is performed on a blood sample, which is to be sent to a reference laboratory for testing using the 5 immunoassays described above. Results of the 5 determinations are entered manually into an Excel® spreadsheet used by the OvaCalc software. This software contains an algorithm which combines the 5 discrete values into a single unitless numerical score from 0.0 to 10.0.

Details of the algorithm appear proprietary, but development is described as an empiric process, based on use of banked samples from academic partners, on a small prospective study of samples from Europe and using a designated subset of samples from the clinical study used to support submission to the FDA. It appears at an undisclosed point in the developmental process as a result of interaction with FDA; separate cut-points were developed for premenopausal and postmenopausal women.

A similar developmental process was described for ROMA by Moore et al. (12) They studied 9 biomarkers and chose human epididymis secretory protein 4 (HE4) and CA 125 because these markers in tandem produced the best performance. The algorithm developed was subsequently modified to include menopausal status and was independently validated. (13) Again, Separate cut-offs were used for premenopausal and postmenopausal women.

The OVA1 is a qualitative serum test that combines immunoassay results for the 5 analytes described above (CA 125, prealbumin, apolipoprotein A-1, beta 2 microglobulin, and transferrin) into a single numerical score. Analytical performance for the test demonstrated good test precision (coefficient of variation (CV) ranging from 1% to 7.4%, depending on the sample levels studied) and good reproducibility (CV from 2.8% to 8.9%). The test appears linear, reagent and samples stable, and there was no observed interference evaluating common endogenous substances (hemoglobin, bilirubin, etc.)

The ROMA test is also a qualitative serum test that combines 2 analytes HE4 EIA and the ARCHITECT CA 125, along with menopausal status into a numerical score. Analytical performance for the ROMA also exhibited good precision with a total CV ranging from 0.49% to 7.72%, depending on both sample values and menopausal status. The reproducibility of the test was acceptable, with a CV that ranged from 0.98 to 25.9%, with highest values observed in patients with low scores, as expected. The reagents are variably stable, and users are instructed to follow package inserts for stability on each analyte used. The test was unaffected by interference with hemoglobin, bilirubin, lipids, or human anti-mouse antibodies (HAMA). However, high levels of rheumatoid factor (more than 500 IU/mL) did appear to cause elevations in test values, and testing in patients with elevated rheumatoid factor is not recommended.

Section Summary

Evidence on the technical performance of these tests has been evaluated by the U.S. Food and Drug Administration (FDA) and is available through the FDA website. This information generally indicates acceptable technical performance for use in clinical care.

Diagnostic Performance

Risk scores for both tests are generated according to the specific algorithm used. In the absence of a standard for either of the risk score signals, accuracy has been defined in terms of clinical performance.

Diagnostic performance of the OVA1 test was evaluated in a single prospective, double-blind clinical study using 27 demographically mixed subject enrollment sites. The study was supported by the commercial sponsor of the test. Patients underwent a complete clinical evaluation prior to surgical intervention, and only patients with planned surgical intervention were included in the study. The pre-surgical process for identifying patients for surgery and for establishing a preliminary diagnosis as benign or malignant were not specifically described but were noted to be based on clinical assessment. The study did require at least one imaging test be performed within 12 weeks of surgery. Presumably, use of this somewhat nonstandardized diagnostic methodology provides information on how the test works in conjunction with real-world decision making. The study enrolled a total of 743 patients with 146 subjects used in the training set and 516 in the testing set. Seventy-four patients were excluded because of missing information or samples. All patients had adnexal masses and were scheduled for surgery. The final prevalence of cancer in the population was 27%.

Using pathologic diagnosis as the gold standard, test performance, when combined with presurgical assessment for benign disease, was as follows in the hands of non-gynecological oncologists:

 

Clinical assessment alone

Clinical assessment with OVA1

Sensitivity

72%*

92%

Specificity

83%

42%

Positive predictive value

61%

37%

Negative predictive value

89%

93%

* Confidence intervals not provided.

Diagnostic performance of the ROMA test was also evaluated in a prospective, blinded clinical trial that was industry-sponsored. The study was conducted at 13 demographically mixed subject enrollment sites. Patients all presented with an adnexal mass and were scheduled to undergo surgery. An Initial Cancer Risk Assessment (ICRA) was performed to determine the detection of benign versus malignant lesions before testing. The prevalence of cancer was 15%.

Using pathologic diagnosis as the gold standard, test performance, when combined with presurgical assessment for benign disease, was as follows in the hands of a mixed population of generalist and specialist physicians:

 

ICRA alone

ICRA with ROMA testing

Sensitivity

77% (66 to 86%)

91% (81 to 96%)

Specificity

84% (80 to 88%)

67% (61 to 71%)

Positive predictive value

46% (17 to 56%)

33% (26 to 40%)

Negative predictive value

96% (93 to 97%

98% (95 to 99%)

Both tests when added to pre-testing clinical assessment produced a fall in the positive predictive value of diagnosis with a small increase in the negative predictive value. The changes observed in the negative predictive value were of uncertain statistical and clinical significance.

Several prospective European studies published in 2012 and 2013 have evaluated the diagnostic accuracy of ROMA compared with other tools for distinguishing between benign and malignant pelvic masses. No similar studies have been published evaluating the diagnostic accuracy of the OVA1 test.

The study with the largest sample size was published by Karlsen and colleagues in 2012. (14) The study included 1218 women presenting with pelvic masses. Prior to diagnosis, HE4 and CA125 levels were obtained, and ROMA and the Risk of Malignancy Index (an index consisting of ultrasound findings, menopausal status and CA125 levels) were calculated. At a fixed sensitivity of 94.4%, the specificity of ROMA was 76.5% and the specificity of RMI was 81.5%. At a fixed specificity of 75%, the sensitivity of ROMA was 94.8% and the sensitivity of RMI was 96.0%. Accuracy of ROMA and RMI were not compared statistically, but appeared to be similar. In another study, Kaijser and colleagues evaluated 360 women with pelvic masses who were scheduled for surgery. (15) The study compared the diagnostic accuracy of ROMA and an ultrasound-based prediction model (LR2) developed by the International Ovarian Tumor Analysis Study (IOTA). Histology was used as the reference standard. The overall performance of LR2 (94% sensitivity and 82% specificity) was significantly better than ROMA (84% sensitivity and 80% specificity). In addition, a study by Van Gorp and colleagues found that, in the hands of radiologists at a cancer institute, subjective assessment by ultrasound was superior to ROMA in discriminating benign from malignant adnexal masses. (16)

Section Summary

The number of studies comparing diagnostic accuracy of the ROMA and OVA1 proteomic tests is small, and, other than studies performed prior to FDA approval, most published studies have been conducted outside of the U.S. Studies have found that ROMA has similar or lower accuracy to other risk prediction measures that use components of the standard workup, such as the RMI and the LR2 measures. There are fewer published studies evaluating the diagnostic accuracy of OVA1.

Clinical Utility

A TEC Assessment was completed in 2012 on “Multi-analyte testing for the evaluation of adnexal masses.” (17) The Assessment included evaluation of both the OVA1 and ROMA tests in regards to their impact on health outcomes. The following conclusions were made:

  • evidence regarding the effect of OVA1 and ROMA and effects on health outcomes is indirect, and based on studies of diagnostic performance of the tests in patients undergoing surgery for adnexal masses.
  • There are no prospective studies on the use of these tests in patients who present with an adnexal mass.
  • There are no studies that report the impact of testing on referral patterns or the impact on health outcomes
  • the studies show improvements in sensitivity and worsening of specificity with the use of the tests in conjunction with clinical assessment, there are problems in concluding that this results in improved health outcomes. The clinical assessment performed in the studies is not well characterized.
  • appears to improve sensitivity for detection of malignancy, however specificity declines so much that most patients test positive.
  • does not appear to improve the sensitivity of testing to a great extent.
  • these issues is some uncertainty regarding the benefit of initial treatment by a gynecologic oncologist beyond the need for reoperation is some cases.

No studies evaluating the clinical utility of OVA1 or ROMA were identified in subsequent literature searches. There is indirect evidence from studies of diagnostic accuracy that compare the ROMA test to other risk prediction measures that use components of the standard workup such as menopausal status, CA 125, and ultrasound results. These studies report that the accuracy risk measures using readily available information are similar or superior to the ROMA test. This evidence suggests that the ROMA test would not improve the accuracy of triage compared to existing measures, and is unlikely to result in benefits such as reduced need for second-look operations.

Section Summary

Direct evidence on the clinical utility of the proteomic tests is lacking. Indirect evidence suggests that, For patients who are considering treatment by a non-gynecologic oncologist, use of proteomic tests will decrease the likelihood that an adnexal mass is categorized as benign when it is actually malignant. This might impact referral patterns to a gynecologic oncologist and decrease the likelihood that a patient will require a second follow-up procedure for comprehensive staging, lymphadenectomy, and/or tumor debulking, but empirical evidence of this is lacking. Indirect evidence from studies of diagnostic accuracy suggest that these proteomic tests are unlikely to improve the accuracy of referral, and unlikely to improve outcomes. Because of the unknown effect on referral patterns, the effect on health outcomes is uncertain. Further prospective studies are needed for both assays to understand their proper role in patient care.

Clinical Input Received through Physician Specialty Societies and Academic Medical Centers

While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted. Results of clinical input in 2012 revealed mixed support for the use of this test as a tool for triaging patients with an adnexal mass. Reviewers agreed that the evidence was insufficient to determine the impact of these tests on referral patterns. For indications other than triaging patients with an adnexal mass, there was a lack of support for use of these tests.

Summary

The OVA1 and ROMA tests have both been analytically validated and clinical performance has been reported in prospective multi-center clinical studies. Changes in the observed sensitivity and negative predictive value of testing compared to clinical assessment has been small and of uncertain diagnostic value. Studies on the diagnostic accuracy of these tests compared to other diagnostic tools have had mixed findings, but do not report that ROMA is superior to other risk prediction tools that use standard clinical information. No studies have been performed that directly evaluated the impact on referral patterns, and no studies have evaluated the impact on health outcomes. Clinical input from academic medical centers and specialty societies did not show consensus that this test improved outcomes when used as a tool to triage patients with adnexal masses. As a result of the evidence and clinical input, these tests are considered investigational pending more information about its performance and impact on outcomes.

Clinical Practice Guidelines and Position Statements

The American Congress of Obstetricians and Gynecologists addressed the use of the OVA1 test in their guidelines on the role of the obstetrician-gynecologist in the early detection of epithelial ovarian cancer, last updated in 2011. (18, 19) This document made the following statements:

  • OVA1 test appears to improve the predictability of ovarian cancer in women with pelvic masses
  • is not a screening test, but may be useful for evaluating women with a pelvic mass
  • utility is not yet established

In May 2013, the Society for Gynecologic Oncology (SGO) issued the following statement on multiplex serum testing for women with pelvic masses: (20)

“Blood levels of five proteins in women with a known ovarian mass have been reported to change when ovarian cancer is present. Tests measuring these proteins may be useful in identifying women who should be referred to a gynecologic oncologist. Recent data have suggested that such tests, along with physician clinical assessment, may improve detection rates of malignancies among women with pelvic masses planning surgery. Results from such tests should not be interpreted independently, nor be used in place of a physician’s clinical assessment. Physicians are strongly encouraged to reference the American Congress of Obstetricians and Gynecologists’ 2011 Committee Opinion “The Role of the Obstetrician-Gynecologist in the Early Detection of Epithelial Ovarian Cancer” to determine an appropriate care plan for their patients. It is important to note that no such test has been evaluated for use as, nor cleared by, the FDA as a screening tool for ovarian cancer. SGO does not formally endorse or promote any specific products or brands.”

The National Institute for Health and Clinical Excellence (NICE) issued guidance in 2011 on the recognition and management of ovarian cancer. (21) These guidelines made the following recommendations:

  • evidence suggests that the combination of HE4 and serum CA125 is more specific, but less sensitive than either marker in isolation.
  • was no evidence to suggest that multiple tumour markers were much better than the two marker combination of serum CA125 and HE4.
  • routine use of CA 125 is recommended; the data on other serum markers is not substantial enough to recommend their use

The National Comprehensive Cancer Network (NCCN) guideline on ovarian cancer (2013, V.2) includes The following statement: (22)

  • has been suggested that specific biomarkers (serum HE4 and CA-125) along with an algorithm (Risk of Ovarian Malignancy Algorithm [ROMA]) may be useful for determining whether a pelvic mass is malignant or benign
  • FDA has approved the use of HE4 and CA-125 for estimating the risk of ovarian cancer in women with a pelvic mass. Currently, the NCCN panel does not recommend the use of these biomarkers for determining the status of an undiagnosed pelvic mass.”

Medicare National Coverage

There is no national coverage determination.

References

  1. Bristow RE, Zahurak ML, Diaz-Montes TP et al. Impact of surgeon and hospital ovarian cancer surgical case volume on in-hospital mortality and related short-term outcomes. Gynecol Oncol 2009; 115(3):334-8.
  2. du Bois A, Rochon J, Pfisterer J et al. Variations in institutional infrastructure, physician specialization and experience, and outcome in ovarian cancer: a systematic review. Gynecol Oncol 2009; 112(2):422-36. .
  3. Hoskins W, Rice L, Rubin S. Ovarian cancer surgical practice guidelines. Society of Surgical Oncology practice guidelines. Oncology (Williston Park) 1997; 11(6):896-900, 903-4.
  4. Vernooij F, Heintz P, Witteveen E et al. The outcomes of ovarian cancer treatment are better when provided by gynecologic oncologists and in specialized hospitals: a systematic review. Gynecol Oncol 2007; 105(3):801-12.
  5. Giede KC, Kieser K, Dodge J et al. Who should operate on patients with ovarian cancer? An evidence-based review. Gynecol Oncol 2005; 99(2):447-61.
  6. Van Holsbeke C, Van Belle V, Leone FP et al. Prospective external validation of the 'ovarian crescent sign' as a single ultrasound parameter to distinguish between benign and malignant adnexal pathology. Ultrasound Obstet Gynecol 2010; 36(1):81-7.
  7. Im SS, Gordon AN, Buttin BM et al. Validation of referral guidelines for women with pelvic masses. Obstet Gynecol 2005; 105(1):35-41.
  8. Medical Devices: Ovarian adnexal mass assessment score test system; Labeling; Black box restrictions. 21 CFR Part 866, Federal Register 2011;76(251):82128-82123.
  9. Fung ET. A recipe for proteomics diagnostic test development: the OVA1 test, from biomarker discovery to FDA clearance. Clin Chem 2010; 56(2):327-9.
  10. U.S. Food and Drug Administration (FDA). 510(k) substantial equivalence determination decision summary: ROMA™ test – K103358. Available online at: http://www.accessdata.fda.gov/cdrh_docs/reviews/K103358.pdf. Last accessed October, 2013.
  11. U.S. Food and Drug Administration (FDA). 510(k) Substantial Equivalence Determination Decision Summary: OVA1™ Test (K081754). Available online at: http://www.accessdata.fda.gov/cdrh_docs/reviews/K081754.pdf. Last accessed October, 2013.
  12. Moore RG, Brown AK, Miller MC et al. The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass. Gynecol Oncol 2008; 108(2):402-8.
  13. Moore RG, Miller MC, Disilvestro P et al. Evaluation of the diagnostic accuracy of the risk of ovarian malignancy algorithm in women with a pelvic mass. Obstet Gynecol 2011; 118(2 Pt 1):280-8.
  14. Karlsen MA, Sandhu N, Hogdall C et al. Evaluation of HE4, CA125, risk of ovarian malignancy algorithm (ROMA) and risk of malignancy index (RMI) as diagnostic tools of epithelial ovarian cancer in patients with a pelvic mass. Gynecol Oncol 2012; 127(2):379-83.
  15. Kaijser J, Van Gorp T, Van Hoorde K et al. A comparison between an ultrasound based prediction model (LR2) and the risk of ovarian malignancy algorithm (ROMA) to assess the risk of malignancy in women with an adnexal mass. Gynecol Oncol 2013; 129(2):377-83.
  16. Van Gorp T, Veldman J, Van Calster B et al. Subjective assessment by ultrasound is superior to the risk of malignancy index (RMI) or the risk of ovarian malignancy algorithm (ROMA) in discriminating benign from malignant adnexal masses. Eur J Cancer 2012; 48(11):1649-56.
  17. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Multi-analyte testing for the evaluation of adnexal masses. TEC Assessments 2012; Volume 27, tab C.
  18. American College of Obstetricians and Gynecologists Committee on Gynecologic Practice. Committee Opinion No. 477: the role of the obstetrician-gynecologist in the early detection of epithelial ovarian cancer. Obstetrics and Gynecology 2011; 117(3):742-6.
  19. American College of Obstetricians and Gynecologists (ACOG). The Role of the Obstetrician Gynecologist in the Early Detection of Epithelial Ovarian Cancer. Available online at: http://www.acog.org/Resources%20And%20Publications/Committee%20Opinions/Committee%20on%20Gynecologic%20Practice/The%20Role%20of%20the%20Obstetrician%20Gynecologist%20in%20the%20Early%20Detection%20of%20Epithelial%20Ovarian%20Cancer.aspx. Last accessed November 8, 2013
  20. Society of Gynecologic Oncologists. Multiplex Serum Testing for Women with Pelvic Mass (May 2013). Available online at: https://www.sgo.org/newsroom/position-statements-2/multiplex-serum-testing-for-women-with-pelvic-mass/. Last accessed November 8, 2013.
  21. National Center for Clinical Excellence (NICE). The recognition and initial management of ovarian cancer 2011. Available online at: http://guidance.nice.org.uk/CG122. Last accessed November 8, 2013.
  22. National Comprehensive Cancer Network (NCCN). Available online at: http://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf. Last accessed November 8, 2013.

Coding

Codes

Number

Description

CPT

84999

Unlisted chemistry procedure

 

81500

Oncology (ovarian), biochemical assays of two proteins (CA-125 and HE4), utilizing serum, with menopausal status, algorithm reported as a risk score (new code effective 1/1/13)

 

81503

Oncology (ovarian), biochemical assays of five proteins (CA-125, apoliproprotein A1, beta-2 microglobulin, transferrin and pre-albumin), utilizing serum, algorithm reported as a risk score (new code effective 1/1/13)

ICD-9 Procedure

   

ICD-9 Diagnosis

220

Benign neoplasm of ovary

 

236.2

Neoplasm of uncertain behavior, ovary

 

239.5

Neoplasm of unspecified nature, other genitourinary organs (includes ovary)

 

789.33, 789.34

Abdominal or pelvic swelling, mass or lump, left upper quadrant and right upper quadrant codes

ICD-10-CM
(effective 10/01/14)

D27.0 – D27.9

Benign neoplasm of ovary, code range

 

D39.10 – D39.12

Neoplasm of uncertain behavior, ovary, code range

 

D49.5

Neoplasm of unspecified nature, of other genitourinary organs (includes ovary)

 

R19.01, R19.02

Right upper quadrant abdominal swelling, mass and lump and left upper quadrant abdominal swelling, mass and lump codes

ICD-10-PCS
(effective 10/01/14)

   

HCPCS

   

Type of Service

Pathology

 

Place of Service

Laboratory

 

Appendix

N/A

History

Date

Reason

06/13/11

Add to Pathology/Laboratory Section - Reviewed by OAP on May 12, 2011. New medical policy.

12/19/12

Replace policy. Policy updated to change the use of the OVA1™ and ROMA tests from medically necessary to investigational for all indications. Rationale updated based on a literature review through September 2012, results of TEC Assessment, and results of clinical vetting. References 7, 13, 17-28 added; others renumbered or removed. New CPT codes added. Policy statement changed as noted.

03/15/13

Update Related Policies. Add 2.03.501.

10/16/13

Update Related Policies. Add 12.04.66 and remove policy 2.04.34 as it was archived.

12/27/13

Replace policy. Policy updated with literature search through September 30, 2013. References 14, 15 and 20 added; other references renumbered or removed. No change to policy statement. Title changed to Proteomic-based Testing Related to Ovarian Cancer. Clarification note added that this policy is only to be used when HE4 is included in the ROMA combination test. When HE4 is billed as an individual test, 12.04.66 – Serum Biomarker Human Epididymis Protein 4 (HE4) should be used.


Disclaimer: This medical policy is a guide in evaluating the medical necessity of a particular service or treatment. The Company adopts policies after careful review of published peer-reviewed scientific literature, national guidelines and local standards of practice. Since medical technology is constantly changing, the Company reserves the right to review and update policies as appropriate. Member contracts differ in their benefits. Always consult the member benefit booklet or contact a member service representative to determine coverage for a specific medical service or supply. CPT codes, descriptions and materials are copyrighted by the American Medical Association (AMA).
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