Original Issue Date (Created): October 1, 2014 Most Recent Review Date (Revised): May 20, 2014 Effective Date: October 1, 2014 POLICY PRODUCT VARIATIONS DESCRIPTION/BACKGROUND RATIONALE DEFINITIONS BENEFIT VARIATIONS DISCLAIMER CODING INFORMATION REFERENCES POLICY HISTORY I. POLICY Measurements of may be considered medically necessary in patients with symptoms suggestive of ovarian cancer or in those with known ovarian cancer. Measurement of may be considered medically necessary in individual patients with other gynecologic malignancies, such as endometrial cancer, in whom baseline levels of have been shown to be elevated. Measurement of is considered investigational in asymptomatic patients as a screening technique for ovarian cancer as there is insufficient evidence to support a conclusion concerning the health outcomes or benefits associated with this procedure. Cross-reference: MP-2.269 Serum Biomarkers for Human Epididydmis Protein 4 (HEA) II. PRODUCT VARIATIONS [N] = No product variation, policy applies as stated [Y] = Standard product coverage varies from application of this policy, see below [N] Capital Cares 4 Kids [N] PPO [N] HMO [N] SeniorBlue HMO [N] SeniorBlue PPO [N] Indemnity [N] SpecialCare [N] POS [Y] FEP PPO* * Refer to FEP Medical Policy Manual MP-2.04.27. The FEP Medical Policy manual can be found at: www.fepblue.org Page 1
III. DESCRIPTION/BACKGROUND is an accepted tool for monitoring patients with known ovarian cancer and other gynecologic malignancies. It has been proposed for use as a screening test in asymptomatic women. is a high-molecular-weight protein antigen that is commonly elevated in patients with known ovarian cancer. may also be elevated in other gynecologic malignancies, such as endometrial cancer, although the association is not as consistent as that with ovarian cancer. has been widely used as a technique to monitor patients with known ovarian cancer or other gynecologic malignancies that, in individual patients, are associated with elevated levels of. Frequently, a rising will be the initial sign of recurrent disease. has also been investigated as a possible screening tool for ovarian cancer, both in the general population and in patients considered at high risk of ovarian cancer. Levels of may also be elevated in nonmalignant conditions, including pregnancy, endometriosis, pelvic inflammatory disease, benign ovarian masses, and without any identifiable cause. IV. RATIONALE for Monitoring and Surveillance of Known Ovarian Cancer and Other Gynecologic Cancers The use of to monitor ovarian cancer recurrence in patients with known ovarian cancer is considered standard practice and is not further discussed. In addition, other gynecologic malignancies, particularly endometrial cancer, may also be associated with CA- 125 in individual cases. If so, levels of may be similarly monitored for cancer recurrence. as a Screening Tool for Ovarian Cancer Most ovarian cancers present in an advanced stage such that complete surgical resection is not possible. Therefore, there has been long-standing interest in developing screening techniques for ovarian cancer. Measurements of and transvaginal ultrasound have been the techniques most commonly investigated. Validation of any oncologic screening technique requires data showing that the screening is a sensitive and relatively specific technique to identify cancers early in the course of the disease, such that prompt treatment results in an improved outcome. A large randomized controlled trial, the Prostate, Lung, Colorectal and Ovarian (PLCO) trial, found that screening with and transvaginal ultrasound did not reduce the rate of ovarian cancer mortality compared with usual care. (1) The study, whose main findings were published in 2011, was conducted at 10 centers in the United States and included 78,216 Page 2
women aged 55 to 74 years-old. Women were randomized to be offered annual screening (n=39,105) or usual care (n=39,111). Women in the intervention group were screened with a blood test and transvaginal ultrasound at baseline. They then underwent annual ultrasound for another 3 years and an annual for another 5 years. The study protocol changed over time; depending on when women were enrolled, they may have been eligible for between 4 and 6 rounds of screening. A total of 28,745 (73.5%) received the baseline screening, 5,508 (14.1%) did not receive screening for a variety of reasons, and 4,852 (12.4%) were excluded because they had undergone oophorectomy. (Women who had oophorectomy were still eligible to be screened for lung cancer and colorectal cancer as part of the PLCO). The primary analysis included all 34,253 women who had not had an oophorectomy prior to study participation. Screening rates for in the usual care group ranged from 2-3% per year. By the fourth follow-up screening, 14,138 (35% of the randomized population) had been screened with. Participants were followed for a maximum of 13 years (median, 12.4 years). There were a total of 118 deaths caused by ovarian cancer in the intervention group (3.1 per 10,000 person-years of follow-up) and 110 deaths in the usual care group (2.6 per 10,000 person-years). The difference in rates was not statistically significant [adjusted mortality rate ratio (RR), 1.18; 95% confidence interval (CI): 0.82 to 1.71). During follow-up, there were 212 cases of ovarian cancer in the intervention group (5.7 per 10,000 person-years) and 176 cases in the usual care group (4.7 per 10,000 person-years). This difference in rates was also not statistically significant (RR, 1.21, 95% CI: 0.99 to 1.48). A total of 1,080 women, out of 3,285 with false-positive results, underwent surgery as part of the diagnostic work-up. Of these, 163 (15%) experienced one or more major complications; this yielded a rate of 20.6 complications for every 100 surgical procedures. Infection was the most common complication, followed by direct surgical complications. The authors noted that the study may not have been able to detect ovarian cancer at an early enough stage to impact health outcomes, as evidenced by the lack of stage shift (decrease in the number of advanced cancers detected in the intervention group compared to the control group). The authors further state that the protocol in the ongoing United Kingdom (UK) Collaborative Trial of Ovarian Cancer Screening (discussed below) might diagnose ovarian cancer earlier and thus have an impact on mortality. An earlier pilot screening trial, published in 1999, included 22,000 postmenopausal women. (2) After the initial baseline screening with, half the women were randomly selected to receive 3 more annual tests, while the other half received no further tests but were followed up by researchers. In the group assigned to receive annual screening, 468 women had elevated levels, and 29 were ultimately referred for a surgical biopsy. Of those referred for biopsy, 6 were diagnosed with ovarian cancer, while the other 23 had false-positive results. Ten more women in the screening group developed ovarian cancer during the 8 years they were followed up by the researchers. This study did not provide data on whether screening reduced the morbidity and mortality of ovarian cancer. Patients with BRCA mutations, or patients with a strong family history of ovarian cancer, are considered at higher risk of ovarian cancer. For example, in patients with a BRCA1 mutation, the risk of ovarian cancer is estimated at 26% by age 76 years. For those with BRCA2 Page 3
mutations, the risk is lower, estimated at 10% by age 70. Similarly, the risk associated with a family history will vary according to the number of affected relatives. Some have suggested that screening may be appropriate in this high-risk subset of patients. For example, in 1997, the Cancer Genetic Studies Consortium developed recommendations for the follow-up care of individuals with BRCA1 and BRCA2 mutations. (3) These recommendations included annual or semi-annual measurements of and transvaginal ultrasound. However, the Cancer Genetics Studies Consortium acknowledges that this screening method was based on expert opinion only with no demonstrated benefit as yet. Ongoing trials United Kingdom (UK) Collaborative Trial of Ovarian Cancer Screening: This study is evaluating multimodal screening, annual screening with testing interpreted with the risk of ovarian cancer algorithm and including transvaginal ultrasound as a second-line test. In addition to the multimodal screening arm, there will a transvaginal ultrasound screening arm and a usual care arm. The study includes postmenopausal women between the ages of 50 and 74 years and the estimated number of participants is 20,000 women. The primary outcome of the study is ovarian cancer mortality. The screening phase of the study will continue until December 31, 2011, and initial follow-up will be complete on December 31, 2014. (4) Summary testing to monitor ovarian cancer and other gynecologic malignancies is considered standard practice. A large published randomized trial, conducted in the United States, found that screening asymptomatic women for ovarian cancer with does not reduce ovarian cancer mortality but does result in unnecessary invasive procedures among women with falsepositive test results. An additional trial evaluating testing of asymptomatic postmenopausal women is ongoing in the U.K. Practice Guidelines and Position Statements as a Screening Tool for Ovarian Cancer National Cancer Care Network (NCCN): Their 2011 ovarian cancer guideline states, randomized data do not yet support routine screening for ovarian cancer in the general population, and routine screening is not currently recommended by any professional society. Some physicians follow women with high-risk factors (e.g. those with BRCA mutations, those with a family history) using monitoring and endovaginal ultrasound; however, prospective validation of these tests remains elusive (5) United States Preventive Services Task Force (USPSTF): Their 2004 statement on screening for ovarian cancer states recommends against routine screening for ovarian cancer (D recommendation). (6) American College of Obstetricians and Gynecologists (ACOG): A December 2002 Committee Opinion notes currently available. Page 4
V. DEFINITIONS N/A VI. BENEFIT VARIATIONS The existence of this medical policy does not mean that this service is a covered benefit under the member's contract. Benefit determinations should be based in all cases on the applicable contract language. Medical policies do not constitute a description of benefits. A member s individual or group customer benefits govern which services are covered, which are excluded, and which are subject to benefit limits and which require preauthorization. Members and providers should consult the member s benefit information or contact Capital for benefit information. VII. DISCLAIMER Capital s medical policies are developed to assist in administering a member s benefits, do not constitute medical advice and are subject to change. Treating providers are solely responsible for medical advice and treatment of members. Members should discuss any medical policy related to their coverage or condition with their provider and consult their benefit information to determine if the service is covered. If there is a discrepancy between this medical policy and a member s benefit information, the benefit information will govern. Capital considers the information contained in this medical policy to be proprietary and it may only be disseminated as permitted by law. VIII. CODING INFORMATION Note: This list of codes may not be all-inclusive, and codes are subject to change at any time. The identification of a code in this section does not denote coverage as coverage is determined by the terms of member benefit information. In addition, not all covered services are eligible for separate reimbursement. Covered when medically necessary: CPT Codes 86304 Current Procedural Terminology (CPT) copyrighted by American Medical Association. All Rights Reserved. Page 5
HCPCS Code Description ICD-9-CM Diagnosis Description Code* 182.0 Malignant neoplasm of body of uterus, corpus uteri, except isthmus 182.1 Malignant neoplasm of body of uterus, isthmus 182.8 Malignant neoplasm of body of uterus, other specified sites of body of uterus 183.0 Malignant neoplasm of ovary and other uterine adnexa, ovary 183.2 Malignant neoplasm of ovary and other uterine adnexa, Fallopian tube 183.3 Malignant neoplasm of ovary and other uterine adnexa, broad ligament 183.4 Malignant neoplasm of ovary and other uterine adnexa, Parametrium 183.5 Malignant neoplasm of ovary and other uterine adnexa, Round ligament 183.8 Malignant neoplasm of ovary and other uterine adnexa, Other specified sites of uterine adnexa 183.9 Malignant neoplasm of ovary and other uterine adnexa, Uterine adnexa, unspecified V10.3 Personal history of malignant neoplasm, breast V16.41 Family history of malignant neoplasm, Ovary *If applicable, please see Medicare LCD or NCD for additional covered diagnoses. The following ICD-10 diagnosis codes will be effective October 1, 2015: ICD-10-CM Diagnosis Description Code* C53.0-C55 Malignant neoplasm of uterus, code range C57.4 Malignant neoplasm of uterine adnexa, unspecified Z80.41 Family history of malignant neoplasm of ovary Z85.3 Family history of malignant neoplasm of ovary Z86.000 Personal history of in-situ neoplasm of the breast *If applicable, please see Medicare LCD or NCD for additional covered diagnoses. Page 6
IX. REFERENCES 1. Buys SS, Partridge E, Black A et al. for the PLCO team. Effect of screening on ovarian cancer mortality: The prostate, lung, colorectal and ovarian (PLCO) cancer screening randomized controlled trial. JAMA 2011; 305: 2295-2303. 2. Jacobs IJ, Skates SJ, MacDonald N et al. Screening of ovarian cancer: a pilot randomized controlled trial. Lancet 1999; 353(9160): 1207-10. 3. Burke W. Daly M. Garber J et al. Recommendations for follow-up care of individuals with an inherited predisposition to cancer. II. BRCA1 and BRCA2. JAMA 1997; 277(12): 997-1003. 4. United Kingdom Collaborative Trial of Ovarian Cancer Screening. Available online at: http://www.instituteforwomenshealth.ucl.ac.uk/academic_research/gynaecologicalcancer/g crc/ukctocs Last accessed September 2011. 5. National Comprehensive Cancer Network. Ovarian Cancer. Clinical practice guidelines in oncology, v2.2011. Available online at: http://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf. Last accessed September 2011. 6. U.S. Preventive Services Task Force. Screening for Ovarian Cancer: Recommendation Statement. May 2004. Available online at: http://www.uspreventiveservicestaskforce.org/3rduspstf/ovariancan/ovcanrs.htm. Last accessed August 2011. 7. The American College of Obstetricians and Gynecologists. ACOG Committee Opinion: number 280, December 2002. The role of the generalist obstetrician-gynecologist in the early detection of ovarian cancer. Obstet Gynecol 2002 Dec; 100(6):1413-6. Other: Centers for Medicare and Medicaid Services (CMS) National Coverage Determination (NCD) 190.28 Tumor Antigen by Immunoassay - CA 125 Effective 01/01/06. CMS [Website]: http://www.cms.gov/medicare-coverage-database/details/ncddetails.aspx?ncdid=130&ncdver=2&docid=190.28&searchtype=advanced&bc=ia AAAAgAAAAAAA%3d%3d& Accessed April 1, 2014. Novitas Solutions. Local Coverage Determination (LCD) L33142 Biomarkers for Oncology. Effective 1/1/14. X. POLICY HISTORY MP 2.271 CAC 5/20/14 Policy criteria removed from MP-2.212 Tumor Markers and Tumor Related Molecular Testing. References updated and rationale added. No changes to policy statements. Policy coded. Page 7
Top Health care benefit programs issued or administered by Capital BlueCross and/or its subsidiaries, Capital Advantage Insurance Company, Capital Advantage Assurance Company and Keystone Health Plan Central. Independent licensees of the BlueCross BlueShield Association. Communications issued by Capital BlueCross in its capacity as administrator of programs and provider relations for all companies. Page 8