Latest Review Date: January 2024

Category:  Surgery                                                                

POLICY:

Autologous or allogeneic hematopoietic stem-cell transplantation is considered investigational to treat advanced stage epithelial ovarian cancer.

POLICY GUIDELINES:

Cord blood transplantation is discussed in greater detail in policy # 439 Placental/Umbilical Cord Blood as a Source of Stem Cells.

Stem cell transplantation to treat germ cell tumors of the ovary is considered separately in policy #412 Hematopoietic Cell Transplantation in the Treatment of Germ-Cell Tumors.

DESCRIPTION OF PROCEDURE OR SERVICE:

Epithelial Ovarian Cancer

Several types of malignancies can arise in the ovary; epithelial carcinoma is the most common. Epithelial ovarian cancer is the fifth most common cause of cancer death in women. New cases and deaths from ovarian cancer in the United States for 2023 were estimated at 19,710 and 13,270, respectively. Most ovarian cancer patients present with extensive disease, and the National Cancer Institute Surveillance, Epidemiology and Results Program reported a 50.8 % 5-year survival for all cases between 2013 and 2019.

Treatment

Currently, management for advanced epithelial ovarian cancer includes cytoreductive surgery and chemotherapy. Approximately 75% of patients present with International Federation of Gynecology and Obstetrics stage III to IV ovarian cancer and are treated with paclitaxel plus a platinum analogue (e.g., cisplatin), the preferred regimen for the newly diagnosed advanced disease. Use of platinum and taxanes has improved progression-free survival and overall survival in advanced disease to between 16 and 21 months and 32 and 57 months, respectively. However, cancer returns in most women, and they die of the disease due to the chemotherapy drug resistance that leads to uncontrolled cancer growth.

Hematopoietic Cell Transplantation

HCT is a procedure in which hematopoietic stem cells are infused to restore bone marrow function in cancer patients who receive bone-marrow-toxic doses of drugs with or without whole body radiotherapy. Hematopoietic stem cells may be obtained from the transplant recipient (autologous HCT) or a donor (allogeneic HCT). They can be harvested from bone marrow, peripheral blood, or umbilical cord blood and placenta shortly after delivery of neonates. Although cord blood is an allogeneic source, the stem cells in it are antigenically “naive” and thus are associated with a lower incidence of rejection or graft-versus-host disease. The use of cord blood is discussed in Medical Policy #439: Placental/Umbilical Cord Blood as a Source of Stem Cells.

HCT is an established treatment for certain hematologic malignancies; however, its use in solid tumors in adults is largely experimental.

KEY POINTS:

The most recent update covered the period through December 29, 2023.

Summary of Evidence

For individuals who have advanced-stage epithelial ovarian cancer who receive HCT, the evidence includes randomized trials and data from case series and registries. Relevant outcomes are overall survival, disease-specific survival, change in disease status, and treatment related mortality and morbidity. Although some of the observational studies have reported longer survival in subsets of patients with advanced epithelial ovarian cancer than patients treated with standard chemotherapy, none of the randomized trial evidence has shown a benefit from HCT in this population. Overall, the evidence has not shown that HCT improves health outcomes in treating epithelial ovarian cancer, including survival, compared with conventional standard doses of chemotherapy. The evidence is insufficient to determine the effects of the technology on health outcomes.

Practice Guidelines and Position Statements

National Comprehensive Cancer Network (NCCN) Guidelines

The current NCCN guidelines on ovarian cancer including fallopian tube cancer and primary peritoneal cancer (v.2.2023) do not address HCT for epithelial ovarian cancer for either newly diagnosed patients, nor for patients with relapsed or refractory disease. However, use of high-dose chemotherapy with HCT received a category 2B recommendation for individuals with certain malignant germ cell tumors demonstrating abnormal tumor markers and definitive recurrent disease and a category 2A recommendation in those with persistently elevated markers and definitive residual disease. NCCN notes that "patients with potentially curable recurrent germ cell disease should be referred to a tertiary care institution for HCT consultation and potentially curative therapy."

Accordingly, NCCN guidelines on HCT (v.3.2023) only reference ovarian germ cell tumors.

U.S. Preventive Services Task Force Recommendations

Not Applicable.

KEY WORDS:

High-Dose Chemotherapy, Ovarian, Epithelial, HCT, hematopoietic cell transplant, epithelial ovarian cancer, autologous, allogeneic

APPROVED BY GOVERNING BODIES:

The FDA regulates human cells and tissues intended for implantation, transplantation or infusion through the Center for Biologics Evaluation and Research, under Code of Federal Regulation (CFR) title 21, parts 1270 and 1271. Hematopoietic stem cells are included in these regulations.

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits.  Group-specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply

FEP: Special benefit consideration may apply. Refer to member’s benefit plan. 

CURRENT CODING:

CPT Codes:

HCPCS:

REFERENCES:

1. American Cancer Society. Cancer Facts & Figures 2023. Atlanta, GA: American Cancer Society; 2023. www.cancer.org/research/cancerfactsstatistics/.
2. Donato ML, Aleman A, Champlin RE, et al. Analysis of 96 patients with advanced ovarian carcinoma treated with high-dose chemotherapy and autologous stem cell transplantation.  Bone Marrow Transplant. Jun 2004; 33(12):1219-1224.
3. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
4. Ledermann JA, Herd R, Maraninchi D, et al. High-dose chemotherapy for ovarian carcinoma: long-term results from the Solid Tumour Registry of the European Group for Blood and Marrow Transplantation (EBMT). Ann Oncol. May  2001; 12(5):693-699.
5. Mobus V, Wandt H, Frickhofen N, et al. Phase III trial of high-dose sequential chemotherapy with peripheral blood stem cell support compared with standard dose chemotherapy for first-line treatment of advanced ovarian cancer: Intergroup trial of the AGO-Ovar/AIO and EBMT. J Clin Oncol. Sep 20 2007; 25(27):4187-4193.
6. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Hematopoietic Cell Transplantation (HCT): Pre-Transplant Recipient Evaluation and Management of Graft-Versus-Host Disease. Version 3.2023. www.nccn.org/professionals/physician_gls/pdf/hct.pdf. 
7. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Ovarian Cancer Including Fallopian Tube Cancer and Primary Peritoneal Cancer. Version 2.2023. www.nccn.org/professionals/physician_gls/PDF/ovarian.pdf.
8. National Cancer Institute, Surveillance Epidemiology and End Results Program. Cancer Stat Facts: Ovarian Cancer. n.d.; https://seer.cancer.gov/statfacts/html/ovary.html. 
9. Papadimitriou C, Dafni U, Anagnostopoulos A, et al. High-dose melphalan and autologous stem cell transplantation as consolidation treatment in patients with chemo sensitive ovarian cancer: Results of a single-institution randomized trial. Bone Marrow Transplant. Mar 2008; 41(6):547-554.
10. Sabatier R, Goncalves A, Bertucci F et al. Are there candidates for high-dose chemotherapy in ovarian carcinoma? J Exp Clin Cancer Res. Oct 16 2012; 31(1):87.
11. Stiff PJ, Veum-Stone J, Lazarus HM, et al. High-dose chemotherapy and autologous stem-cell transplantation for ovarian cancer: an autologous blood and marrow transplant registry report. Ann Intern Med Oct 03 2000; 133(7):504-515.
12. Stiff PJ, Bayer R, Kerger C, et al. High-dose chemotherapy with autologous transplantation for persistent/relapsed ovarian cancer: a multivariate analysis of survival for 100 consecutively treated patients. J Clin Oncol. April 1997; 15(4):1309-1317.

POLICY HISTORY:

Medical Policy Group, January 2010 (2)

Medical Policy Administration Committee, January 2010

Available for comment January 26-March 11, 2010

Medical Policy Group, November 2010 (1): Description updated, Key Points updated, no policy change

Medical Policy Group, December 2011 (3): 2012 Code Updates: Verbiage update to Codes 38208, 38209 & 38230; Added Code 38323

Medical Policy Group, February 2012 (2): Updated Description and Key Points

Medical Policy Group, January 2013 (2): 2013 Update to Key Points. No change in the policy statement.

Medical Policy Panel, November 2013

Medical Policy Group, November 2013 (3):  Update to Description, Key Points and References; no change in policy statement

Medical Policy Panel, November 2014

Medical Policy Group, November 2014 (3): Updates to Description, Key Points and Approved Governing Bodies. No Policy change.

Medical Policy Panel, January 2016.

Medical Policy Group, February 2016 (2): Updates to Description, Key Points, Approved Governing Bodies, Key Words, and References.  No change to policy statement.

Medical Policy Panel, January 2017

Medical Policy Group, January 2017 (7): Updates to Title, Description, added Key Points. No new References added. No change to policy statement.

Medical Policy Group, December 2017. Annual Coding Update 2018. Added new CPT code 38222 effective 1/1/18 to the Current Coding section.  Updated verbiage for revised CPT codes 38220 and 38221.

Medical Policy Panel, January 2018

Medical Policy Group, January 2018 (7): 2018 Updates to Description, Key Points and References. Policy statement clarified to add “advanced stage” associated with epithelial ovarian cancer; no change in intent.

Medical Policy Panel, January 2019

Medical Policy Group, February 2019 (3): Updates to Key Points and References. No change to policy statement or intent.

Medical Policy Panel, January 2020

Medical Policy Group, January 2020 (3): 2020 Updates to Key Points and References. Policy Guidelines section added. No changes to policy statement or intent.

Medical Policy Panel, January 2020

Medical Policy Group, January 2020 (3): Updates to Description, Key Points, and References.

Medical Policy Panel, January 2022

Medical Policy Group, January 2022 (3): 2022 Updates to Description, Key Points, and Practice Guidelines and Position Statements. No changes to policy statement or intent.

Medical Policy Panel, January 2023

Medical Policy Group, January 2023 (3): 2023 Updates to Description, Key Points, Practice Guidelines and Position Statements, and References. No changes to policy statement or intent.

Medical Policy Panel, January 2024

Medical Policy Group, January 2024 (3): Updates to Description, Key Points, Benefit Application and References. No changes to policy statement or intent.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.