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Horizon BCBSNJ
Uniform Medical Policy ManualSection:Drugs
Policy Number:078
Effective Date: 05/15/2020
Original Policy Date:05/25/2010
Last Review Date:04/14/2020
Date Published to Web: 06/21/2010
Sipuleucel-T (Provenge®)



The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.

Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.


Prostate cancer is the second leading cause of cancer-related deaths among American men with an estimated incidence of 186,320 cases and an estimated number of 28,660 deaths in 2008. The majority of cases are diagnosed at a localized stage and are treated with prostatectomy or radiation therapy. Although many men experience disease control after primary therapy, approximately 20% to 40% will eventually experience disease recurrence. In these men, androgen deprivation typically achieves temporary tumor control in 80% to 85% of patients. However, virtually all patients who live long enough will eventually progress and develop metastases despite androgen deprivation. This castration-resistant or androgen-independent stage presents a significant clinical challenge. Current treatment options include secondary hormone therapy, chemotherapy, and investigational agents. At this stage of metastatic disease, docetaxel has been demonstrated to confer a survival benefit of 1.9 to 2.4 months in randomized clinical trials. Chemotherapy with docetaxel causes adverse effects in large proportions of patients, including alopecia, fatigue, neutropenia, neuropathy, and other symptoms. Because of the difficulty of treatment and its side effects, most patients defer docetaxel until the cancer recurrence is symptomatic.

Cancer immunotherapy has been investigated as a treatment which might 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 interval is thought to be relatively low, and it is thought that an effective immune response against the cancer during this time period could effectively delay or prevent progression. Such a delay could allow effective chemotherapy such as docetaxel to be deferred or delayed until necessary, thus providing an overall survival benefit.

Sipuleucel-T (Provenge®) is a new therapeutic agent used in the treatment of asymptomatic or minimally symptomatic, metastatic castrate resistant (hormone refractory) prostate cancer. It consists of specially treated dendritic cells obtained from the patient with leukapheresis. The cells are then exposed exposed ex vitro to proteins that contain prostate antigens and immunologic stimulating factors, and then reinfused back into the patient. The cells are administered as 3 intravenous (IV) infusions, each infusion given approximately 2 weeks apart. The proposed mechanism of action is that the treatment stimulates the patient’s own immune system to resist the spread of cancer.

(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance)

The requirements of the Horizon BCBSNJ Sipuleucel-T (Provenge®) Program may require a precertification/prior authorization via MagellanRx Management. These requirements are member-specific: please verify member eligibility and requirements through the Horizon Provider Portal (www.horizonblue.com/provider). Ordering clinicians should request pre-certification from MagellanRx Management at ih.magellanrx.com or call 1-800-424-4508 (when applicable).

1. Sipuleucel-T (Provenge®) is medically necessary for the FDA-approved treatment of prostate cancer in members who meet all of the following criteria:

    • The prescriber is a specialist in the area of the patient’s diagnosis (e.g. oncologist) or has consulted with a specialist in the area of the patient’s diagnosis
    • Adult men(18 years or older)
    • Androgen-independent (hormone refractory) prostate cancer has been confirmed by histology
    • Serum testosterone less than 50 ng/dL in men who have not undergone prior surgical castration
    • Radiological evidence of peripheral metastases (see Informational Note A)
    • Evidence of progressive disease based on successive radiographic studies or prostate specific antigen (PSA) progression as defined by PSA Consensus Criteria (see Informational Note B)
    • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (see Informational Note C)
    • Asymptomatic or minimally symptomatic (see Informational Note D)
    • Member has no hepatic metastases
    • Member has not previously received therapy with sipuleucel-T

      A. In clinical trials with sipuleucel-T, patients with visceral (liver, lung or brain) metastases were excluded from treatment.
      B. NCCN guidelines state that rising PSA should not be used as the sole criteria for progression, but instead an assessment of clinical and radiographic criteria should be incorporated. When PSA progression is the only evidence of progressive disease, the PSA Consensus Criteria recommend that two consecutive increases in PSA be documented over a previous reference value. The first increase in PSA should occur at a minimum of 1 week from the reference value, and should be confirmed. It is recognized that PSA fluctuations may occur, and in this situation a general trend toward increasing PSA over time will be considered as evidence of progressive disease. In either situation, the PSA should measure no less than 5 2.0 ng/mL because it is more difficult to interpret PSA changes at lower values. It is also advisable to estimate a pretreatment PSA doubling time (PSA-DT) if at least three values are available with 4 or more weeks apart, but it is not recommended to delay treatment simply to estimate PSA-DT.
      C. ECOG performance status criteria assess disease progression and its effect on daily living. The grading criteria are summarized below:
    Grade 0: Fully active, able to carry on all pre-disease performance without restriction.
        Grade 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work.
        Grade 2: Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
        Grade 3: Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
        Grade 4: Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
    Grade 5: Dead.
      D. In clinical trial with sipuleucel-T, patients were excluded if they required opioid analgesics for cancer pain, had cancer-related bone pain, required systemic corticosteroids, had visceral metastases, or received prior immunotherapy.
      E. In a study by Kantoff, et al labeled the IMPACT trial, sipuleucel-T was studied in 512 patients with castration-resistant prostate cancer. Patients in both placebo and sipuleucel-T groups underwent leukapheresis for three treatments given every two weeks. There was a relative risk reduction of 22% in the sipuleucel-T group translating to a 4.1-month improvement in survival time, however it does not decrease the tumor size or prolong time to progression of disease. A editorial review of the IMPACT trial suggests the survival improvement may be due to a flaw in the design of this trial. Because patients in the placebo group were leukapheresed as well and did not receive the full amount of their cells back (up to 65% were frozen), the patients in the placebo group may have had poorer outcomes.]
2. When sipuleucel-T (Provenge®) is considered medically necessary, it will be covered for one time only as a series of 3 infusions administered at approximately 2-week intervals.
[INFORMATIONAL NOTE: Based on the FDA approved package insert, patients should be premedicated with oral acetaminophen and an antihistamine, such as diphenhydramine, before receiving Provenge®]

3. Sipuleucel-T (Provenge®) is considered medically necessary for the following off label indications that are 2A or better recommendations on National Comprehensive Cancer Network (NCCN) compendium. Refer to National Comprehensive Cancer Network: Drugs and Biologics Compendium - Sipuleucel-T. Available at: https://www.nccn.org/professionals/drug_compendium/content/.

4. Other uses of sipuleucel-T (Provenge®) are considered investigational including, but not limited to, more than 3 complete doses for metastatic castrate-resistant prostate cancer.

Medicare Coverage

Per National Coverage Determination (NCD) for Autologous Cellular Immunotherapy Treatment 110.22, CMS has determined that autologous cellular immunotherapy treatment - sipuleucel-T; PROVENGE® will be covered for individuals with asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone refractory) prostate cancer. Novitas Solutions, Inc, the Local Medicare Carrier for jurisdiction JL, has determined that all off-label uses of autologous cellular immunotherapy treatment - sipuleucel-T; PROVENGE® for the treatment of prostate cancer, including carcinoma in situ of the prostate, are lacking sufficient scientific data to support the use and are therefore considered not reasonable and necessary. For eligibility and coverage, please refer to NCD 110.22 and LCD L35094. Available to be accessed at Novitas Solutions, Inc., Medical Policy Search page: https://www.novitas-solutions.com/webcenter/portal/MedicareJL/pagebyid?contentId=00024370

Medicaid Coverage

For Horizon NJ Health members, please follow this link for the corresponding HNJH drug policy https://services3.horizon-bcbsnj.com/ddn/NJhealthWeb.nsf


Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.


Sipuleucel-T (Provenge)
Provenge (Sipuleucel-T)
Cellular Immunotherapy for Prostate Cancer
Prostate Cancer Vaccine
Vaccine, Prostate Cancer


1. Sipuleucel-T (Provenge®) Prescribing Information. Dendreon Corporation. Seattle, WA. July 2017.

2. Higano CS, Schellhammer PF, Small EJ, et al. Integrated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer. Cancer. 2009;115(16):3670-9.

3. Small EJ, Schellhammer PF, Higano CS, et al. Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J Clin Oncol. 2006;24(19):3089-94.

4. Rini BI, Weinberg V, Fong L, et al. Combination immunotherapy with prostatic acid phosphatase pulsed antigen-presenting cells (Provenge) plus bevacizumab in patients with serologic progression of prostate cancer after definitive local therapy. Cancer. 2006;107(1):67-74.

5. Berry DL, Moinpour CM, Jiang CS, et al. Quality of life and pain in advanced stage prostate cancer: results of a Southwest Oncology Group randomized trial comparing docetaxel and estramustine to mitoxantrone and prednisone. J Clin Oncol 2006;24(18)2828-35.

6. Tannock IF, de Wit R, Berry WR et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351(15)1502-12.

7. U.S. Food and Drug Administration. Cellular, Tissue and Gene Therapies Advisory Committee Meeting, March 29, 2007. Statistical Briefing Document. Available at http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4291B1_03a.htm. Accessed January 11, 2012.

8. Bubley GJ, Carducci M, Dahut W, et al. Eligibility and Response Guidelines for Phase II Clinical Trials in Androgen-Independent Prostate Cancer: Recommendations from the Prostate-Specific Antigen Working Group. J Clin Oncol. 1999;17(11):3461-3467.

9. Oken MM, Creech RH, Tormey, DC, et al. Toxicity and Response Criteria Of The Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5:649-655.

10. Bok RA. Treatment of prostate cancer: therapeutic potential of targeted immunotherapy with APC 8015. Ther Clin Risk Manag. 2008;4(1):79-85.

11. Sipuleucel-T. MICROMEDEX® 1.0 (Healthcare Series). 2010. Available at: http://www.thomsonhc.com. Accessed February 24, 2014.

12. Sipuleucel-T. Gold Standard 2010. Available at: http://www.clinicalpharmacology.com. Accessed February 24, 2014.

13. Sipuleucel-T. National Comprehensive Cancer Network (NCCN). NCCN Drugs and Biologics Compendium. Available online at www.nccn.org. Last accessed March 21, 2020.

14. Scher HI, Halabi S, Tannock I, et al. Design and End Points of Clinical Trials for Patients With Progressive Prostate Cancer and Castrate Levels of Testosterone: Recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol. 2008;26(7):1148-1159.

15. Prostate Cancer. National Comprehensive Cancer Network (NCCN) NCCN Guidelines Version 2020. Available online at https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf. Last accessed March 30, 2020.

16. Thompson I, Thrasher JB, Aus G, et al. Guideline for the management of clinically localized prostate cancer: 2007 update. J Urol. 2007;177(6):2106–31.

17. Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. New Engl J Med. 2010;363(5): 411–422.

18. Graff JN and Chamberlain ED. Sipuleucel-T in the treatment of prostate cancer: an evidence-based review of its place in therapy. Core Evid. 2015;10:1-10.

19. Goldberg JM. Immunotherapy of sarcomas. Curr Opin Oncol. 2013;25(4):390-397.

(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)



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    Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.

    The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy