Cellular Immunotherapy for Prostate Cancer

POLICY NUMBER

A.8.01.53

DESCRIPTION

Sipuleucel-T (Provenge) is a therapeutic agent used to treat asymptomatic or minimally symptomatic, castration-resistant, metastatic prostate cancer. The agent comprises specially treated dendritic cells obtained from the patient through leukapheresis. The cells are then exposed in vitro to proteins that contain prostate antigens and immunologic-stimulating factors and reinfused into the individual. The proposed mechanism of action is that the treatment stimulates the individual's own immune system to resist cancer spread.

Prostate Cancer

Prostate cancer is the second leading cause of cancer-related deaths among American men, with an estimated incidence of 313,780 cases and an estimated 35,770 deaths in 2025. In most cases, prostate cancer is diagnosed at a localized stage and is treated with prostatectomy or radiotherapy. However, some patients are diagnosed with metastatic or recurrent disease after treatment of localized disease.

Treatment

Androgen ablation is the standard treatment for metastatic or recurrent disease. Most patients who survive long enough eventually develop androgen-independent (castration-resistant) prostate cancer. At this stage of metastatic disease, docetaxel, a chemotherapeutic agent, has demonstrated a survival benefit of 1.9 to 2.4 months in randomized clinical trials. Chemotherapy with docetaxel causes adverse events in large proportions of patients, including alopecia, fatigue, neutropenia, neuropathy, and other symptoms. Trials evaluating docetaxel included both asymptomatic and symptomatic patients, and results have suggested a survival benefit for both groups. Because of the burden of treatment and its adverse events, most patients defer docetaxel treatment until cancer recurrence is symptomatic.

Cancer immunotherapy has been investigated as a treatment that could be instituted at the point of detection of androgen-independent metastatic disease before significant symptomatic manifestations have occurred. The quantity of cancer cells in the patient during this time is thought to be relatively low, and it is thought that an effective immune response to cancer during this interval could effectively delay or prevent progression. Such a delay could allow a course of effective chemotherapy, such as docetaxel, to be deferred or delayed until necessary, thus providing an overall survival benefit.

In 2010, the U.S. Food and Drug Administration approved Provenge® (sipuleucel-T; Dendreon Corp) under a biologics licensing application for "the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone refractory) prostate cancer." Approval was contingent on the manufacturer conducting a postmarketing study, based on a registry design, to assess the risk of cerebrovascular events in 1,500 menwith prostate cancer who receive sipuleucel-T.

Also, see the Genetic and Protein Biomarkers for the Diagnosis and Cancer Risk Assessment of Prostate Cancer medical policy.

POLICY

Sipuleucel-T therapy (Provenge®) may be considered medically necessary in the treatment of asymptomatic or minimally symptomatic, androgen-independent (castration-resistant) metastatic prostate cancer.

Sipuleucel-T therapy (Provenge®) is considered investigational in all other situations, including but not limited to, treatment of hormone-responsive prostate cancer, treatment of those with moderate-to-severe symptomatic metastatic prostate cancer, and treatment of visceral (liver, lung or brain) metastases.

POLICY EXCEPTIONS

Federal Employee Program (FEP) may dictate that all FDA-approved devices, drugs or biologics may not be considered investigational and thus these devices may be assessed only on the basis of their medical necessity.

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

A.  consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

B.  appropriate with regard to standards of good medical practice; and

C.  not solely for the convenience of the Member, his or her Provider; and

D.  the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of medical necessity, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.

Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.

POLICY HISTORY

07/22/2010: Approved by Medical Policy Advisory Committee.

09/28/2011: Policy reviewed; no changes.

09/27/2012: Policy reviewed; no changes.

05/07/2013: Added HCPCS code Q2043 to the Code Reference section.

11/06/2013: Policy reviewed; no changes.

09/04/2014: Policy reviewed; description updated. Investigational policy statement revised to change "those with" to "treatment of." Intent of policy statement unchanged.

08/26/2015: Medical policy revised to add ICD-10 codes.

10/27/2015: Policy description updated regarding estimated data for 2015. Medically necessary policy statement updated to change "hormone-refractory" to "castration-resistant." Policy guidelines updated to add medically necessary and investigative definitions.

05/26/2016: Policy number A.8.01.53 added.

08/14/2017: Policy description updated. Policy statements unchanged.

08/15/2018: Policy description updated regarding estimated data for prostate cancer in 2018. Policy statements unchanged. Policy Guidelines updated.

08/21/2019: Policy reviewed; no changes.

09/03/2020: Policy reviewed; no changes.

12/03/2021: Policy description updated. Policy statements unchanged. Policy Guidelines updated to change "Nervous/Mental Conditions" to "Mental Health Disorders" and "Medically Necessary" to "medical necessity."

08/25/2022: Policy description updated. Policy statements unchanged.

08/15/2023: Policy description updated regarding new data for prostate cancer. Policy statements unchanged.

08/15/2024: Policy description updated regarding new data for prostate cancer. Policy statements unchanged.

09/16/2025: Policy description updated regarding new data for prostate cancer. Policy statements unchanged.

SOURCE(S)

1. Blue Cross Blue Shield Association policy # 8.01.53

2. (Provenge®) Prescribing Information

3. www.fda.gov

   - Provenge® Questions and Answers

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.     

The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.

Covered Codes

CPT copyright American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.