Non-Discrimination Statement and Multi-Language Interpreter Services information are located at the end of this document. Coverage for services, procedures, medical devices and drugs are dependent upon benefit eligibility as outlined in the member's specific benefit plan. This Medical Coverage Guideline must be read in its entirety to determine coverage eligibility, if any. This Medical Coverage Guideline provides information related to coverage determinations only and does not imply that a service or treatment is clinically appropriate or inappropriate. The provider and the member are responsible for all decisions regarding the appropriateness of care. Providers should provide BCBSAZ complete medical rationale when requesting any exceptions to these guidelines. The section identified as Description defines or describes a service, procedure, medical device or drug and is in no way intended as a statement of medical necessity and/or coverage. The section identified as Criteria defines criteria to determine whether a service, procedure, medical device or drug is considered medically necessary or experimental or investigational. State or federal mandates, e.g., FEP program, may dictate that any drug, device or biological product approved by the U.S. Food and Drug Administration (FDA) may not be considered experimental or investigational and thus the drug, device or biological product may be assessed only on the basis of medical necessity. Medical Coverage Guidelines are subject to change as new information becomes available. For purposes of this Medical Coverage Guideline, the terms "experimental" and "investigational" are considered to be interchangeable BLUE CROSS, BLUE SHIELD and the Cross and Shield Symbols are registered service marks of the Blue Cross and Blue Shield Association, an association of independent Blue Cross and Blue Shield Plans. All other trademarks and service marks contained in this guideline are the property of their respective owners, which are not affiliated with BCBSAZ. Description: Alpha-fetoprotein-L3 (AFP-L3) is a glycoprotein that has been investigated as a biomarker for hepatocellular cancer (HCC). The Wako AFP-L3 laboratory test has received 510K marketing clearance from the Food and Drug Administration. O544.10.docx Page 1 of 5
Criteria: Evaluation of AFP-L3 biomarkers for the screening, diagnosis or monitoring of suspected or known hepatocellular cancer is considered experimental or investigational based upon: 1. Insufficient scientific evidence to permit conclusions concerning the effect on health outcomes, and 2. Insufficient evidence to support improvement of the net health outcome, and 3. Insufficient evidence to support improvement of the net health outcome as much as, or more than, established alternatives, and 4. Insufficient evidence to support improvement outside the investigational setting. Resources: Literature reviewed 05/01/18. We do not include marketing materials, poster boards and nonpublished literature in our review. The BCBS Association Medical Policy Reference Manual (MPRM) policy is included in our guideline review. References cited in the MPRM policy are not duplicated on this guideline. 1. 2.04.46 BCBS Association Medical Policy Reference Manual. Alpha-Fetoprotein-L3 for Detection of Hepatocellular (Liver) Cancer. Re-issue date 06/11/2009; issue date 04/09/2008. 2. Bertino G, Ardiri A, Malaguarnera M, Malaguarnera G, Bertino N, Calvagno GS. Hepatocellualar carcinoma serum markers. Semin Oncol. Aug 2012;39(4):410-433. 3. Chaiteerakij R, Zhang X, Addissie BD, et al. Combinations of Biomarkers and Milan Criteria for Predicting Hepatocellular Carcinoma Recurrence after Liver Transplantation. Liver Transpl. Mar 17 2015. 4. Cheng J, Wang W, Zhang Y, et al. Prognostic role of pre-treatment serum AFP-L3% in hepatocellular carcinoma: systematic review and meta-analysis. PLoS One. 2014;9(1):e87011. 5. Choi JY, Jung SW, Kim HY, et al. Diagnostic value of AFP-L3 and PIVKA-II in hepatocellular carcinoma according to total-afp. World J Gastroenterol. Jan 21 2013;19(3):339-346. 6. Gao J, Song P. Combination of triple biomarkers AFP, AFP-L3, and PIVAKII for early detection of hepatocellular carcinoma in China: Expectation. Drug discoveries & therapeutics. 2017;11(3):168-169. 7. Hayashi M, Shimizu T, Hirokawa F, et al. Clinicopathological risk factors for recurrence within one year after initial hepatectomy for hepatocellular carcinoma. Am Surg. May 2011;77(5):572-578. O544.10.docx Page 2 of 5
Resources: 8. Kitai S, Kudo M, Izumi N, et al. Validation of three staging systems for hepatocellular carcinoma (JIS score, biomarker-combined JIS score and BCLC system) in 4,649 cases from a Japanese nationwide survey. Dig Dis. 2014;32(6):717-724. 9. Kumada T, Toyoda H, Tada T, et al. High-sensitivity Lens culinaris agglutinin-reactive alphafetoprotein assay predicts early detection of hepatocellular carcinoma. J Gastroenterol. Mar 2014;49(3):555-563. 10. Li B, Li B, Guo T, et al. The Clinical Values of Serum Markers in the Early Prediction of Hepatocellular Carcinoma. BioMed research international. 2017;2017:5358615. 11. Ma H, Sun X, Chen L, et al. Multiplex Immunochips for High-Accuracy Detection of AFP-L3% Based on Surface-Enhanced Raman Scattering: Implications for Early Liver Cancer Diagnosis. Analytical chemistry. Sep 5 2017;89(17):8877-8883. 12. Moriya S, Morimoto M, Numata K, et al. Fucosylated fraction of alpha-fetoprotein as a serological marker of early hepatocellular carcinoma. Anticancer Res. Mar 2013;33(3):997-1001. 13. Nakao K, Ichikawa T. Recent topics on alpha-fetoprotein. Hepatol Res. Aug 2013;43(8):820-825. 14. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) Hepatobiliary Cancers. 02/14/2018, 2012. 15. Nguyen-Dinh SH, Do A, Pham TND, Dao DY, Nguy TN, Chen MS, Jr. High burden of hepatocellular carcinoma and viral hepatitis in Southern and Central Vietnam: Experience of a large tertiary referral center, 2010 to 2016. World journal of hepatology. Jan 27 2018;10(1):116-123. 16. Sterling RK, Wright EC, Morgan TR, et al. Frequency of elevated hepatocellular carcinoma (HCC) biomarkers in patients with advanced hepatitis C. Am J Gastroenterol. Jan 2012;107(1):64-74. 17. Toyoda H, Kumada T, Tada T. Highly sensitive Lens culinaris agglutinin-reactive alphafetoprotein: a new tool for the management of hepatocellular carcinoma. Oncology. 2011;81 Suppl 1:61-65. 18. UpToDate. Clinical features and diagnosis of primary heptacellular carcinoma. 11/20/2017, 11/16/2016. 19. Yi X, Yu S, Bao Y. Alpha-fetoprotein-L3 in hepatocellular carcinoma: a meta-analysis. Clin Chim Acta. Oct 21 2013;425:212-220. O544.10.docx Page 3 of 5
Non-Discrimination Statement: Blue Cross Blue Shield of Arizona (BCBSAZ) complies with applicable Federal civil rights laws and does not discriminate on the basis of race, color, national origin, age, disability or sex. BCBSAZ provides appropriate free aids and services, such as qualified interpreters and written information in other formats, to people with disabilities to communicate effectively with us. BCBSAZ also provides free language services to people whose primary language is not English, such as qualified interpreters and information written in other languages. If you need these services, call (602) 864-4884 for Spanish and (877) 475-4799 for all other languages and other aids and services. If you believe that BCBSAZ has failed to provide these services or discriminated in another way on the basis of race, color, national origin, age, disability or sex, you can file a grievance with: BCBSAZ s Civil Rights Coordinator, Attn: Civil Rights Coordinator, Blue Cross Blue Shield of Arizona, P.O. Box 13466, Phoenix, AZ 85002-3466, (602) 864-2288, TTY/TDD (602) 864-4823, crc@azblue.com. You can file a grievance in person or by mail or email. If you need help filing a grievance BCBSAZ s Civil Rights Coordinator is available to help you. You can also file a civil rights complaint with the U.S. Department of Health and Human Services, Office for Civil Rights electronically through the Office for Civil Rights Complaint Portal, available at https://ocrportal.hhs.gov/ocr/portal/lobby.jsf, or by mail or phone at: U.S. Department of Health and Human Services, 200 Independence Avenue SW., Room 509F, HHH Building, Washington, DC 20201, 1 800 368 1019, 800 537 7697 (TDD). Complaint forms are available at http://www.hhs.gov/ocr/office/file/index.html Multi-Language Interpreter Services: O544.10.docx Page 4 of 5
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