Therapeutic Radiopharmaceuticals for Prostate Cancer

POLICY NUMBER

A.5.01.43

DESCRIPTION

Prostate cancer is the second leading cause of cancer-related deaths among American men with 299,010 new cases and 35,250 disease-related deaths estimated for 2024. About 6 in 10 cases of prostate cancer are diagnosed in men who are 65 years of age or older, and the disease is rare in men under 40 years of age. Prostate cancer disproportionally affects African American men and Caribbean men of African ancestry compared to men of other races. The disease is less common in Asian American, Hispanic, and Latino men than in non-Hispanic White men. The reasons for these racial and ethnic differences are not well understood. Typically, prostate cancer is typically suspected based on increased levels of prostate-specific antigen (PSA) upon screening.

Grading

Clinical staging is based on the digital rectal exam and biopsy results. T1 lesions are not palpable while T2 lesions are palpable but appear to be confined to the prostate. T3 lesions extend through the prostatic capsule, and T4 lesions are fixed to or invade adjacent structures. The most widely used grading scheme for a prostate biopsy is the Gleason system. It is an architectural grading system ranging from 1 (well-differentiated) to 5 (poorly differentiated); the score is the sum of the primary and secondary patterns. A Gleason score of 6 or less is low-grade prostate cancer that usually grows slowly; 7 is an intermediate grade; 8 to 10 is a high-grade cancer that grows more quickly. A revised prostate cancer grading system has been adopted by the National Cancer Institute and the World Health Organization. A cross-walk of these grading systems are shown in the table below.

Prostate Cancer Grading Systems

Treatment

Early localized disease can usually be treated with surgery and radiotherapy, although active surveillance may be adopted in men whose prostate cancer is unlikely to cause major health problems during their lifespan or for whom the treatment might be dangerous. In patients with inoperable or metastatic disease, treatment consists of hormonal therapy and possibly chemotherapy. Androgen deprivation therapy (ADT) is generally the initial treatment for patients with advanced prostate cancer. Unfortunately, while ADT is effective at producing tumor response and improving quality of life, most patients' disease will eventually progress on ADT.

Castration-Resistant Prostate Cancer

Prostate cancer that progresses while the patient is on ADT is referred to as castration-resistant prostate cancer (CRPC). Androgen pathways are important in the progression of CRPC, therefore, even after progression, continued ADT is generally used in conjunction with other treatments. Several drugs have been developed that either inhibit enzymes involved in androgen production or inhibit the androgen receptor, such as abiraterone and enzalutamide. Taxane chemotherapy with docetaxel or cabazitaxel may also be used after progression. Immunotherapy (sipuleucel-T) or radium 223 are additional options for select men.

Prostate-Specific Membrane Antigen–Positive Metastatic Castration-Resistant Prostate Cancer

Prostate-specific membrane antigen (PSMA) is a transmembrane glutamate carboxypeptidase that is highly expressed on prostate cancer cells and high PSMA expression is an independent biomarker of poor prognosis. Metastatic lesions are PSMA-positive in most patients with metastatic CRPC (mCRPC) and high expression has been independently associated with reduced survival. More recently, radioligand therapies such as lutetium Lu 177 vipivotide tetraxetan (Lu-177-PSMA-617) have demonstrated the ability to selectively target prostate cancer cells in patients who have PSMA-positive mCRPC.

Radionuclide Therapy: Lutetium Lu 177 vipivotide tetraxetan

Lu-177-PSMA-617 is a radioligand therapeutic agent with 2 components: a drug that delivers the therapy to cancer cells and a radioactive particle. In the case of Lu-177-PSMA-617, the delivery vehicle is PSMA-617 and the radioactive component is lutetium-177. Upon binding of Lu-177-PSMA-617 to PSMA-expressing cells, the beta-minus emission from lutetium-177 delivers radiation to PSMA-expressing cells, as well as to surrounding cells, and induces DNA damage which can lead to cell death. Patients should be selected for treatment with Lu-177-PSMA-617 using gallium Ga 68 gozetotide or an approved PSMA-11 imaging agent based on PSMA expression in tumors.

On March 23, 2022, Lu-177-PSMA-617 (Pluvicto™) was approved by the U.S. Food and Drug Administration (FDA) for use in adults with PSMA-positive mCRPC who have been treated with androgen receptor (AR) pathway inhibition and taxane-based chemotherapy.

On March 23, 2022, gallium Ga 68 gozetotide (Locametz®) was approved by the U.S. FDA as a radioactive diagnostic agent indicated for positron emission tomography (PET) of PSMA-positive lesions in men with prostate cancer: 1) with suspected metastasis who are candidates for initial definitive therapy; or 2) with suspected recurrence based on elevated serum PSA level; or 3) for selection of patients with metastatic prostate cancer, for whom lutetium Lu 177 vipivotide tetraxetan PSMA-directed therapy is indicated.

On May 26, 2022, piflufolastat F 18 (Pylarify®) was approved by the U.S. FDA as a radioactive diagnostic agent indicated for PET of PSMA-positive lesions in men with prostate cancer with: 1) suspected metastasis who are candidates for initial definitive therapy or 2) suspected recurrence based on elevated serum PSA level.

On December 17, 2021, gallium Ga 68 gozetotide (Illuccix®) was approved by the U.S. FDA as a radioactive diagnostic agent indicated for PET of PSMA-positive lesions in men with prostate cancer with: 1) suspected metastasis who are candidates for initial definitive therapy or 2) suspected recurrence based on elevated serum PSA level. The labeling was updated in March 2023 to include selection of patients with metastatic prostate cancer for whom treatment with Lu-177-PSMA-617 is indicated.

Related medical policies –

• Oncologic Applications of Positron Emission Tomography (PET) Scanning

• Therapeutic Radiopharmaceuticals for Neuroendocrine Tumors

POLICY

Therapeutic radiopharmaceuticals for prostate cancer using Lutetium (Lu) 177 vipivotide tetraxetan (Lu-177-PSMA-617), may be considered medically necessary for the treatment of adults with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) and with 1 or more PSMA-positive lesions and/or metastatic disease that is predominately PSMA-positive and with no dominant PSMA-negative metastatic lesions, who have been treated previously with androgen receptor-directed therapy and a taxane-based chemotherapy.

Therapeutic radiopharmaceuticals for prostate cancer using Lu-177-PSMA-617 is considered investigational for the treatment of prostate cancer when the above criteria are not met.

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.

Lutetium Lu 177 vipivotide tetraxetan

Lutetium Lu 177 vipivotide tetraxetan (Lu-177-PSMA-617) is a radiopharmaceutical and should be used by or under the control of physicians who are qualified by specific training and experience in the safe use and handling of radiopharmaceuticals, and whose experience and training have been approved by the appropriate governmental agency authorized to license the use of radiopharmaceuticals.

The recommended dose of Lu-177-PSMA-617 (Pluvicto™) is 7.4 GBq (200 mCi) every 6 weeks for up to 6 doses.

Patients should be well-hydrated during treatment.

Refer to the prescribing information for Lu-177-PSMA-617 for recommended dosage modifications for adverse reactions. The management of adverse reactions may require temporary dose interruption (extending the dosing interval from every 6 weeks up to every 10 weeks), dose reduction, or permanent discontinuation of treatment with Lu-177-PSMA-617. The dose of Lu-177-PSMA-617 may be reduced by 20% to 5.9 GBq (160 mCi) once; the dose should not be re-escalated.

Lu-177-PSMA-617 should be discontinued permanently if the patient develops any of the following:

• Recurrent Grade 3 or higher myelosuppression after one dose reduction

• Grade 3 or higher renal toxicity

• Recurrent renal toxicity after one dose reduction

• Recurrent Grade 3 dry mouth after one dose reduction

• Recurrent Grade 3 or higher gastrointestinal toxicity after one dose reduction

• Aspartate aminotransferase or alanine aminotransferase greater than 5 times the upper limit of normal in the absence of liver metastases

• Any unacceptable toxicity

• Any serious adverse reaction that requires treatment delay of greater than 4 weeks

• Any recurrent Grade 3 or 4 or persistent and intolerable Grade 2 adverse reaction after one dose reduction

The table below describes the grading of severity used in the Common Toxicity Criteria for Adverse Events (version 4.03).

Common Toxicity Criteria for Adverse Events, Version 4.03

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

08/01/2023: New policy added. Approved by the Medical Policy Advisory Committee.

09/22/2023: Policy description updated regarding new data for prostate cancer and treatment indications. Medically necessary policy statement and Policy Guidelines updated with minor wording changes.

01/10/2025: Policy description updated to remove information regarding radiopharmaceuticals. Added new data regarding prostate cancer. Policy statements unchanged.

SOURCE(S)

Blue Cross Blue Shield Association policy # 5.01.43

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.

Medically Necessary Codes

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