Blue Cross Blue Shield - Iowa Radium-223 Coverage

Coverage and Medical Necessity Criteria

Initial and dosing criteria

Covered when ALL of the following are met

Medically necessary criteria for up to 6 injections: Patient has castration-resistant prostate cancer with symptomatic skeletal (bone) metastases

FDA indication and policy requirement

No visceral disease: No evidence of visceral metastases on imaging within the last 30 days

Imaging requirement to exclude visceral metastatic disease

Concurrent therapy restriction: Radium-223 will not be used concurrently with other chemotherapy or biologic therapy

Concurrent systemic cytotoxic or biologic therapy contraindicated per policy

Hematologic baseline and subsequent thresholds: Patient meets baseline hematologic criteria (ANC ≥1.5 x10^9/L, platelets ≥100 x10^9/L, hemoglobin ≥10 g/dL) and meets pre-dose criteria for subsequent injections (ANC ≥1.0 x10^9/L, platelets ≥50 x10^9/L)maximum 6 injections

Follow label guidance for holding/discontinuing if counts do not recover

Androgen-deprivation therapy: Patient may remain on androgen-deprivation therapy to maintain castrate testosterone level (<50 ng/dL)

Per NCCN guidance

Initial therapy coverage

Covered when ALL of the following are met

Indication and disease state: Patient has castration-resistant prostate cancer with symptomatic bone metastases and no known visceral metastatic disease

Supported by AUA/SUO, NCCN, and FDA indications

Continuation of ADT: Patient is continuing androgen-deprivation therapy as indicated to maintain castrate testosterone (<50 ng/dL)

Document serum testosterone per guideline when applicable

Sequencing considerations: Consider prior docetaxel use or suitability per NICE guidance (radium-223 may be used after docetaxel or when docetaxel is contraindicated or not suitable)

Guideline-informed sequencing; not an absolute requirement in this policy

Safety monitoring and long-term risks:

The policy designates radium‑223 (Xofigo®) as investigational when it is used outside the specified coverage criteria. Examples of such investigational uses include: concomitant use with chemotherapy or biologic therapy, administration beyond six injections, and repeat courses after a prior radium‑223 treatment. Other indications not meeting the criteria in this policy are also considered investigational. These points are explicitly listed in the policy’s investigational section and align with the FDA prescribing information noting that safety and efficacy beyond six injections and with concomitant chemotherapy have not been established.

Radium‑223 is indicated for patients with castration‑resistant prostate cancer who have symptomatic bone metastases and no known visceral metastatic disease. The AUA/SUO guideline specifies use for patients without known visceral disease or lymphadenopathy >3 cm. NCCN guidance states radium‑223 should not be used in patients with visceral metastases and recommends against combining it with docetaxel or other systemic therapies except for androgen‑deprivation therapy (ADT). The FDA label also cautions against concomitant chemotherapy because of additive myelosuppression and notes concomitant use with other systemic therapies (outside ADT) is not recommended except in clinical trials.

There are no additional explicit exclusions listed in the provided excerpt beyond the investigational and contraindicated combinations noted elsewhere. The policy cites multiple guideline and trial references (AUA/SUO, NCCN, NICE, ALSYMPCA trial and product prescribing information) to support the coverage criteria and safety considerations, but detailed exclusion lists beyond those referenced are not provided in this excerpt.

Any use that does not meet the stated coverage criteria may be considered investigational and is subject to denial. Examples called out by the policy include treatment in the presence of visceral metastases, concurrent administration with chemotherapy or biologic therapy, receipt of a prior radium‑223 course, and administration beyond the maximum of 6 injections. Providers should ensure documented medical necessity and adherence to the listed eligibility criteria to avoid denial.

The policy and cited guidance advise against combining radium‑223 with docetaxel or other systemic therapies apart from continued ADT except within clinical trials. This recommendation reflects concerns about additive myelosuppression and the absence of demonstrated safety/efficacy for these combinations outside research settings. Concomitant use with bone‑protecting agents such as denosumab or zoledronic acid is permitted per guidance and does not negate radium‑223’s survival benefit.

The provided excerpt does not enumerate conditions explicitly labeled as 'not medically necessary' beyond stating that uses not meeting the policy’s coverage criteria are investigational and may be denied. Detailed medical‑necessity adjudication is managed per the full policy language and payer procedures; however, the excerpt makes clear that nonconforming uses (for example, concurrent chemotherapy, visceral metastases, prior course, or >6 injections) are considered investigational.

Coding, Billing, and Laboratory Requirements

Codes table referencedmixed

No codes listed

Drug/Agent (narrative)mixed

Radium Ra 223 dichloride

FDA-indicated agent for treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases, and no known visceral metastatic disease (as described in document).

Radiopharmaceutical HCPCSHCPCSCovered

A9606

Radium RA-223 dichloride, therapeutic per microcurie.

CPT (not specified)CPT

No code(s)

CPT entries in document are blank/not specified.

Service and placemixed

Radiopharmaceuticals Oncology	Type of Service
Outpatient	Place of Service

Hematologic thresholds — pre-dose and subsequent lab minimums

Baseline ANC≥ 1.5 x 10^9/L prior to first dose

Baseline platelets≥ 100 x 10^9/L prior to first dose

Baseline hemoglobin≥ 10 g/dL prior to first dose

Subsequent-dose ANC≥ 1.0 x 10^9/L prior to each subsequent dose

Subsequent-dose platelets≥ 50 x 10^9/L prior to each subsequent dose

Action if counts do not recoverDiscontinue radium-223 if counts do not return to required levels within 6–8 weeks despite supportive care

Documentation, Authorization, and Billing Actions for Providers

Prior Authorization

Prior Authorization Required

Prior approval is not required for Radium Ra 223 dichloride (Xofigo®); however, clinical criteria must be met for medical necessity and documentation must be submitted with the request.

Prior Authorization: Not applicable — prior approval not required, but criteria below must be met and documented.

Billing Rule

Billing and Coding for Radium-223

Radium RA-223 dichloride should be reported using HCPCS code A9606. Include appropriate place-of-service and revenue codes on the claim and retain clinical documentation to support medical necessity.

Billing code: HCPCS A9606 — Radium RA-223 dichloride, therapeutic, per microcurie.

Dosing, Administration, and Regimen Details

Regimen	Details
Administration schedule	Six injections given at 4‑week intervals (total of 6 doses); administered as a slow intravenous injection over ~1 minute.
Monitoring	Hematologic evaluation at baseline and prior to every dose to monitor for bone marrow suppression (ANC, platelets, hemoglobin).
Hematologic thresholds	Before first dose: ANC >1.5 x10^9/L, platelets >100 x10^9/L, hemoglobin >10 g/dL. Before subsequent doses: ANC >1.0 x10^9/L, platelets >50 x10^9/L. If values do not recover within 6–8 weeks despite supportive care, discontinue further radium‑223.
Maximum courses	Safety and efficacy beyond 6 injections have not been studied; additional treatment beyond 6 injections is not supported by the label.

Indication	Coverage-relevant guidance
FDA/NCCN/AUA indication	Monotherapy for adults with castration‑resistant prostate cancer and symptomatic bone metastases with no known visceral metastatic disease.
Concurrent systemic therapy	Not recommended in combination with docetaxel or other systemic therapies except androgen‑deprivation therapy (ADT); concomitant denosumab or zoledronic acid is acceptable. Concomitant chemotherapy generally not recommended outside clinical trials due to additive myelosuppression.
Visceral metastases	Should not be used in patients with known visceral metastases.
Safety consideration	Radium‑223 may increase fracture risk when given with abiraterone; follow guideline cautions and consider bone‑protecting agents per recommendations.

Source / context	Policy note
Prescribing information (Xofigo) - dosing and monitoring	Radium Ra‑223 dichloride is indicated for treatment of bone metastases from castration‑resistant prostate cancer; label specifies 6 injections at 4‑week intervals, IV administration, and required hematologic monitoring prior to each dose.
Label safety statements	Safety and efficacy beyond six injections have not been studied; safety and efficacy of concomitant chemotherapy with radium‑223 have not been established; concomitant use with chemotherapy is not recommended outside clinical trials.
Investigational / alternative uses	Uses in other solid tumors and osteosarcoma are discussed in the literature but are investigational and not established by the prescribing information.

Therapy Line and Sequencing

informational

Informational: Radium-223 is an alpha-emitting radiopharmaceutical that targets bone metastases by forming complexes with hydroxyapatite and delivering localized alpha-particle radiation; FDA approved May 2013 for CRPC with symptomatic bone metastases and no known visceral disease.

Background clinical mechanism and approval context

not_specified

Not specified: Specific line-of-therapy placement is not explicitly defined in this policy; guideline sources (NCCN, AUA/SUO, NICE) provide context for sequencing and use.

See guidelines for local sequencing decisions

salvage

Laboratory and Biomarker Thresholds

Biomarker thresholds — key lab/biomarker requirements

Biomarker: TestosteroneSerum testosterone < 50 ng/dL required to define CRPC (castrate level)

Biomarker: PSA trendSequential rise in PSA may indicate castration resistance when testosterone <50 ng/dL

Imaging requirementBone scan within past 60 days showing new or worsening bone metastases supports CRPC with bone mets

Key Terms and Definitions

CRPC with bone metastases — definition and criteria summary

DefinitionCastration-resistant prostate cancer (CRPC) with symptomatic bone metastases: serum testosterone <50 ng/dL plus either sequential PSA rise or new/worsening bone mets on bone scan

Visceral disease exclusionNo known visceral metastatic disease on imaging within the past 30 days

Treatment contextCandidates should be receiving or remain on androgen-deprivation therapy to maintain castrate testosterone when applicable

radium-223 — Radium Ra 223 dichloride (Xofigo)

Agent nameRadium Ra 223 dichloride (Xofigo)

Dosing schedule6 intravenous injections given at 4-week intervals (slow IV over ~1 minute)

Clinical Background and Rationale

Radium‑223 is an alpha‑emitting radiopharmaceutical that behaves like calcium and localizes to areas of increased bone turnover by binding to bone mineral (hydroxyapatite). Its alpha emissions deliver highly localized cytotoxic radiation to bone metastases, contributing to symptomatic benefit and overall survival benefit demonstrated in pivotal trials.

OpenPayer

Radium Ra 223 Dichloride (Xofigo) — Coverage Criteria