DESCRIPTION
Hematopoietic stem-cell transplantation (HSCT) refers to a procedure in which hematopoietic stem cells are infused to restore bone marrow function in cancer patients who receive bone-marrow-toxic doses of cytotoxic drugs with or without whole body radiation therapy. Hematopoietic stem cells may be obtained from the transplant recipient (autologous HSCT) or from a donor (allogeneic HSCT). They can be harvested from bone marrow, peripheral blood, or umbilical cord blood shortly after delivery of neonates.
Germ-cell tumors are composed primarily of testicular neoplasms (seminomas or nonseminomatous tumors) but also include ovarian and extragonadal germ-cell tumors (e.g., retroperitoneal or mediastinal tumors). Germ-cell tumors are classified according to their histology, stage, prognosis, and response to chemotherapy.
Histologies include seminoma, embryonal carcinoma, teratoma, choriocarcinoma, yolk sac tumor, and mixed germ-cell tumors. Seminomas are the most common; all other types are collectively referred to as nonseminomatous germ-cell tumors. Tumors with mixed histology or seminomas with elevated alpha fetoprotein (due to mixture with nonseminomatous components) are categorized as nonseminomatous tumors.
Germ-cell tumors prognostic factor categories are based on histology, site, and extent of primary tumor, and on serum marker levels. Markers used for germ-cell tumors include human beta-chorionic gonadotropin (hCG), lactate dehydrogenase (LDH), and alpha fetoprotein (AFP).
Good-risk pure seminomas can be at any primary site, in the absence of non pulmonary visceral metastases or marker elevations.
Good-risk nonseminoma tumors are testicular or retroperitoneal tumors in the absence of non pulmonary visceral metastases with slightly raised levels of marker elevation (S-1).
Intermediate-risk pure seminomas have non pulmonary visceral metastases with or without elevated HCG and/or LDH.
Intermediate risk nonseminoma tumors or those with mixed histology are testicular or retroperitoneal tumors in the absence of non pulmonary visceral metastases with moderate levels (S-2) of marker elevation.
There are no poor-risk pure seminomas.
Poor-risk nonseminoma tumors or those with mixed histology have mediastinal primary tumors, or non pulmonary visceral metastases, or the highest level (S3) of marker elevations.
Therapy for germ-cell tumors is generally dictated by stage, risk, subgroup, and tumor histology. The probability of long-term continuous complete remission diminishes with each successive relapse.
This medical policy only addresses the use of hematopoietic stem cell transplantation for germ cell tumors, including testicular tumors. For the use of tandem high dose chemotherapy with hematopoietic stem cell support for other conditions/diseases refer to Tandem High Dose Chemotherapy with Hematopoietic Stem Cell Support.
POLICY
Single autologous hematopoietic stem-cell transplantation as salvage therapy for germ-cell tumors is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Tandem or sequential autologous hematopoietic stem-cell transplantation for the treatment of testicular tumors is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Autologous hematopoietic stem-cell transplantation as a component of first-line treatment for germ-cell tumors is considered investigational.
Tandem or sequential autologous hematopoietic stem-cell transplantation to treat germ-cell tumors of any stage, (except as noted above for treatment of certain testicular tumors), is considered investigational.
Allogeneic hematopoietic stem-cell transplantation to treat germ-cell tumors, including, but not limited to its use as therapy after prior failed autologous hematopoietic stem-cell transplantation is considered investigational.
See also:
Autologous Hematopoietic Stem-Cell Transplantation for Malignant Astrocytomas and Gliomas
Hematopoietic Stem-Cell Transplantation for Miscellaneous Solid Tumors in Adults
Pancreas / Pancreas-Kidney / Pancreatic Islet Cell Transplantation
Tandem High Dose Chemotherapy with Hematopoietic Stem Cell Support
MEDICAL APPROPRIATENESS
Hematopoietic stem-cell transplantation for treatment of germ cell tumors is medically appropriate if ANY ONE of the following criteria are met
Single autologous transplant used as salvage therapy in an individual with germ-cell tumors and ANY ONE of the following:
The individual has favorable prognostic factors and has failed a previous course of conventional dose salvage chemotherapy
The HSCT is initial treatment of first relapse (i.e., without a course of conventional-dose salvage chemotherapy) in individuals with unfavorable prognostic factors
The individual has platinum-refractory disease.
Tandem or sequential transplantation for the treatment of an individual with testicular tumors and ANY ONE of the following:
The treatment is salvage therapy
The individual has platinum-refractory disease
IMPORTANT REMINDER
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.
ADDITIONAL INFORMATION
The overall cure rates for testicular germ cell tumors of 95% (80% for metastatic disease) have been achieved through accurate risk stratification and sequential well-designed studies. Some patients who are refractory to initial treatments are experiencing improved survival benefit from second or third-line salvage therapy with high-dose chemotherapy and autologous stem-cell support.
The International germ cell consensus classification: A prognostic factor based staging system for metastatic germ cell cancers has provided the staging classification used by NCCN and ASCO.
The 2010 NCCN guideline for the treatment of testicular cancer states that high-dose chemotherapy with autologous stem cell support is the preferred option in relapsing individuals and in those with incomplete response to conventional chemotherapy. Patients with unfavorable prognostic factors for conventional salvage therapy and those requiring third line salvage therapy are also candidates for HDCT with stem cell support. The guidelines do not address the use of tandem or sequential HSCT in the treatment of testicular tumors.
The role of tandem or sequential therapy has been investigated in one Phase II study, one randomized study, and two retrospective studies. The research has found improved survival and decreased mortality in refractory patients and those with metastatic disease.
There is scant data in the literature to support the use of allogeneic HSCT in the treatment of germ-cell tumors.
SOURCES
American Society of Clinical Oncology. (2007, February). International germ cell consensus classification: A prognostic factor based staging system for metastatic germ cell cancers. Retrieved July 14, 2010 from http://jco.ascopubs.org/cgi/content/abstract/15/2/594.
BlueCross BlueShield Association. Medical Policy Manual. (4:2010). Hematopoietic stem cell transplantation in the treatment of germ cell tumors (8.01.35). Retrieved June 10, 2010 from Blue Web. (13 articles and/or guidelines reviewed)
Cancer Care Ontario. (2009, January). Stem cell transplantation in adults: Recommendations. Retrieved July 15, 2009 from http://www.guideline.gov/content.aspx?id=14435&search=cancer+care+ontario+stem+cell+transplantation+in+adults
Complete Guide to Medicare Coverage Issues [Computer software]. (2007, November) Stem cell transplantation (NCD 110.8.1, p. 2-54 to 2-55). Ingenix.
Einhorn, L., Williams, S., Chamness, A., Brames, M., Perkins, S., & Abonour, R. (2007).High-dose chemotherapy and stem-cell rescue for metastatic germ-cell tumors. New England Journal of Medicine, 357 (4), 340-348. (Level 3 Evidence - Independent)
Feldman, D., Bosl, G., Sheinfeld, J., & Motzer, R. (2008) Medical treatment of advanced testicular cancer. JAMA. 299 (6), 672-684. (Level 2 Evidence - Independent)
Lazaus, H., Stiff, P., Carreras, J., Logan, B., Akar, L., Bolwell, B., et al. (2007). Utility of single versus tandem autotransplants for advanced testes/germ cell cancer: A center for international blood and marrow transplant analysis. Biology of Blood and Marrow Transplantation. 13 (7), 778-789. (Level 2 Evidence - Industry sponsored)
Motzer, R., Nichols, C., Margolin, K., Bacik, J., Richardson, P., Vogelzang, N., et al. (2007). Phase III randomized trial of conventional dose chemotherapy with or without high dose chemotherapy and autologous hematopoietic stem cell rescue as first line treatment for patients with poor prognosis metastatic germ cell tumors. Journal of Clinical Oncology. 25 (3), 247-256. (Level 2 Evidence - Industry sponsored)
Muller, A., Ihorst, G., Waller, C., Dolken, G., Finke, J., & Engelhardt, M. (2006). Intensive chemotherapy with autologous peripheral blood stem-cell transplantation during a 10-year period in 64 patients with germ-cell tumor. Biology of Blood and Marrow Transplantation. 12 (3), 355-365. (Level 3 Evidence - Independent)
National Comprehensive Cancer Network. (2010, April). NCCN clinical practice guidelines in oncology™. Testicular cancer (V.2.2010). Retrieved June 11, 2010 from http://www.nccn.org/professionals/physician_gls/PDF/testicular.pdf.
Tennessee Code Annotated. §56-7-2504 (1995). Policyholders/Part 25 Mandated Insurer or Plan Options. Cancer treatment. Retrieved August 23, 2010 from http://www.michie.com/tennessee/lpext.dll?f=templates&fn=main-h.htm&cp=tncode.
ORIGINAL EFFECTIVE DATE: 12/11/2010
MOST RECENT REVIEW DATE: 12/11/2010
ID_BA
Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.
This document has been classified as public information.