CurrentBlue Cross Blue Shield - South DakotaPolicy N/A

Radium Ra 223 Dichloride (Xofigo)

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Defines medical necessity, investigational uses, and clinical requirements for coverage of radium Ra 223 dichloride (Xofigo) for adults with castration-resistant prostate cancer (CRPC) who have symptomatic bone metastases and no known visceral metastatic disease; affects providers submitting claims to Blue Cross Blue Shield - South Dakota/Wellmark.

Policy Summary

PayerBlue Cross Blue Shield - South Dakota

PolicyRadium Ra 223 Dichloride (Xofigo) — coverage criteria

Policy CodePolicy N/A

Change TypeAnnual review / renewal (no material change)

Effective DateSep 1, 2017

Last ReviewSep 1, 2025

Next Review DateN/A

Key ActionDocument clinical evidence of symptomatic bone metastases, recent imaging showing no visceral disease, and baseline/pre-dose hematologic values; limit therapy to a maximum of six injections given every 4 weeks.

SourceLink

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CurrentBlue Cross Blue Shield - South DakotaPolicy N/A

Radium Ra 223 Dichloride (Xofigo)

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Policy Summary

PayerBlue Cross Blue Shield - South Dakota

PolicyRadium Ra 223 Dichloride (Xofigo) — coverage criteria

Policy CodePolicy N/A

Change TypeAnnual review / renewal (no material change)

Effective DateSep 1, 2017

Last ReviewSep 1, 2025

Next Review DateN/A

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

6max injections

≥1.5→≥1.0ANC thresholds

≥100→≥50Platelet thresholds

A9606HCPCS code

Category 1NCCN recommendation

AnnualPolicy review

Coverage and Medical Necessity Criteria

Initial Therapy / Medically Necessary

Covered when ALL of the following are met

Medically necessary coverage criteria: 1) Diagnosis of castration-resistant prostate cancer (CRPC) with bone metastases defined as serum testosterone < 50 ng/dL plus either a sequential rise in PSA or worsening/new bone metastases on bone scan within the past 60 days despite androgen-deprivation therapy; 2) Symptomatic skeletal (bone) metastases; 3) No evidence of visceral metastatic disease on imaging within the last 30 days; 4) Radium-223 will not be used concurrently with chemotherapy or biologic therapy (concomitant chemotherapy not recommended outside clinical trials); 5) Patient meets baseline hematologic parameters prior to the initial dose (ANC ≥1.5 x10^9/L, platelets ≥100 x10^9/L, hemoglobin ≥10 g/dL) and meets subsequent-dose thresholds (ANC ≥1.0 x10^9/L, platelets ≥50 x10^9/L); 6) Planned regimen does not exceed six injections given at 4-week intervals; 7) Patient may remain on androgen-deprivation therapy to maintain castrate testosterone level (<50 ng/dL).See individual criteria for hematologic and dosing thresholds

Follow FDA label and NCCN guidance; discontinue if blood counts do not recover within 6–8 weeks.

Investigational Uses

Investigational / Not covered

Investigational or not medically necessary uses: Use is considered investigational or not medically necessary when any of the following are present: indication other than CRPC with symptomatic bone metastases; concomitant use with chemotherapy or biologic therapy (outside clinical trials); prior receipt of a course of radium-223; treatment beyond six injections; use in pediatric patients or diagnoses such as osteosarcoma (refer to Off-label Drug Use policy).N/A

Insufficient evidence of net health benefit for these uses; concomitant systemic therapy may increase myelosuppression.

Coverage criteria for radium-223

Covered when ALL of the following are met

Indication and disease: Patient has castration-resistant prostate cancer with symptomatic bone metastases and no known visceral metastatic disease (e.g., no visceral metastases or lymphadenopathy >3 cm).

Supported by NCCN Category 1 and AUA/SUO guidance.

Concurrent therapy: Patient will continue androgen-deprivation therapy (ADT) to maintain castrate testosterone levels where applicable; radium-223 should not be combined with chemotherapy except in clinical trials. Concomitant denosumab or zoledronic acid is acceptable.

Avoid combination with systemic chemotherapy or other radiopharmaceuticals due to additive myelosuppression; radium-223 may increase fracture risk with abiraterone.

Prior therapy considerations: Consider prior use of docetaxel; per NICE, radium-223 may be used in patients who have had docetaxel or when docetaxel is contraindicated or unsuitable. Specific sequencing may vary by guideline and clinical context.

Local step-therapy policies may require assessment of prior docetaxel use.

Coverage is not provided for uses that do not meet the specified medical necessity criteria. Specifically, all other indications beyond castration‑resistant prostate cancer with symptomatic bone metastases are excluded. Prior receipt of a full course of radium‑223 (Xofigo®) and administration beyond six injections are considered investigational. The policy also lists combination use with chemotherapy or biologic therapy among excluded indications unless performed within the context of a clinical trial.

Use of radium‑223 (Xofigo®) in patients with known visceral metastases is excluded; the NCCN and product labeling specify the indication as symptomatic bone metastases with no known visceral metastatic disease. Concomitant use with chemotherapy or other systemic anticancer therapies (other than ongoing androgen‑deprivation therapy) is not recommended outside clinical trials because of the potential for additive myelosuppression; the FDA label and radiation therapy guidance advise against combining radium‑223 with chemotherapy except in a trial setting.

No additional explicit exclusions are stated in this excerpt beyond those already listed elsewhere in the policy and coding section. Providers should follow the documented exclusion and investigational lists when evaluating requests for coverage.

Concomitant administration of radium‑223 with chemotherapy or biologic therapies and treatment courses that exceed six injections are considered not medically necessary or investigational due to insufficient evidence of net health benefit and concern for additive bone marrow toxicity. The FDA labeling further notes that safety and efficacy of concomitant chemotherapy have not been established and that the safety and efficacy beyond six injections have not been studied.

Use of radium‑223 outside the indicated population of symptomatic, bone‑only metastatic CRPC—for example, patients with visceral metastases or asymptomatic bone metastases—is discouraged and may be deemed not medically necessary. NICE guidance additionally restricts use to patients who have received docetaxel or for whom docetaxel is contraindicated or unsuitable, highlighting clinical sequencing considerations.

Within the excerpted sections of the policy there are no additional explicit statements labelled as 'not medically necessary' beyond the conditions already identified (concomitant chemotherapy/biologic therapy and treatment beyond six injections, and use outside symptomatic bone‑only mCRPC).

Billing and Coding

Codes table referencedmixed

No codes listed

Radiopharmaceutical HCPCSHCPCSCovered

A9606

Radium RA-223 dichloride, therapeutic per microcurie.

CPT (not provided)CPT

No code(s)

No CPT codes provided in this excerpt.

Hematologic thresholds (ANC, platelets, hemoglobin) — baseline and subsequent dose thresholds

Baseline ANCAbsolute neutrophil count (ANC) ≥ 1.5 x 10^9/L prior to the first dose

Baseline plateletsPlatelet count ≥ 100 x 10^9/L prior to the first dose

Baseline hemoglobinHemoglobin ≥ 10 g/dL prior to the first dose

Subsequent-dose ANCAbsolute neutrophil count (ANC) ≥ 1.0 x 10^9/L prior to subsequent doses

Subsequent-dose plateletsPlatelet count ≥ 50 x 10^9/L prior to subsequent doses

Failure to recoverDiscontinue radium-223 if blood counts do not recover to required levels within 6–8 weeks despite supportive care

Provider Requirements, Authorization & Documentation

Note

Prior Approval

Prior approval is not applicable for radium-223 at the time of this policy; coverage is determined by meeting the medical necessity criteria and the maximum of six injections.

Prior approval: Not applicable — coverage is based on meeting medical necessity criteria and dosing limits (maximum of 6 injections).

Prior Authorization

Authorization for radium-223

Radium-223 (Xofigo®) is authorized when medical necessity criteria for castration‑resistant prostate cancer with symptomatic bone metastases and no known visceral disease are met. Authorization should confirm the indication (CRPC with symptomatic bone metastases), castrate status (ADT maintained with serum testosterone <50 ng/dL), and that there is no evidence of visceral metastases on imaging within the prior 30 days.

Indication required: CRPC with symptomatic bone-only metastases (no known visceral metastatic disease).
Documentation to support: recent imaging (≤30 days) showing no visceral metastases; documentation of symptomatic skeletal metastases; serum testosterone to confirm castrate state (<50 ng/dL).

Dosing, Administration and Limits

Regimen	Route / Rate	Schedule	Maximum # Injections	Notes
Radium-223 (Xofigo) dosing regimen	Intravenous; slow IV injection over ~1 minute	Every 4 weeks	6	Administer per FDA label; monitor hematologic parameters at baseline and prior to each dose; discontinue if counts do not recover within 6–8 weeks.

Product	Indication (coverage)	Exclusions / Concomitant Therapy	Coverage Status
Radium Ra-223 dichloride (Xofigo®)	Treatment of castration-resistant prostate cancer (CRPC) with symptomatic bone metastases and no known visceral metastatic disease	Not to be used concurrently with chemotherapy or biologic therapy outside clinical trials; avoid combination with docetaxel or other systemic therapies except ADT; do not use in patients with known visceral metastases	Covered with criteria

Topic	Guidance / Billing
Product labeling for administration	Therapeutic administration per product labeling; follow FDA-approved dosing and monitoring (hematologic checks before each dose).
Billing code	Report radium-223 per microcurie using HCPCS code A9606 on claims; use appropriate CPT, revenue, and ICD diagnosis codes as applicable.

Required Laboratory and Biomarker Thresholds

Serum testosterone — castrate status threshold

Required castrate testosterone levelSerum testosterone < 50 ng/dL is required to define castrate status for eligibility

Documentation timingTestosterone level used to confirm ongoing ADT/ castrate state per policy guidelines

Guideline alignmentMaintain ADT to keep testosterone <50 ng/dL in accordance with NCCN guidance

Hematologic thresholds (ANC, platelets, hemoglobin) — baseline and subsequent dose thresholds

Baseline ANCANC ≥ 1.5 x 10^9/L prior to the first radium-223 dose

Baseline plateletsPlatelets ≥ 100 x 10^9/L prior to the first radium-223 dose

Key Definitions

Definition — CRPC with bone metastases

DefinitionCRPC with bone metastases: serum testosterone < 50 ng/dL PLUS either sequential rise in PSA OR worsening/new bone metastases on bone scan within the past 60 days despite androgen-deprivation therapy

Castrate-state requirementSerum testosterone <50 ng/dL is required to establish castrate status

Temporal imaging criterionBone scan changes (worsening or new lesions) must be within the past 60 days to meet definition

Definition — Radium-223 (Xofigo) as an alpha-emitting radiopharmaceutical

Agent descriptionRadium Ra 223 dichloride (Xofigo) is an alpha-particle-emitting radiopharmaceutical used to treat bone metastases in CRPC

Mechanism noteAlpha-emitting radiopharmaceutical that targets bone metastases by localizing to areas of increased bone turnover (bone-seeking)

Placement in Treatment Sequence

not explicitly specified

Line of therapy not explicitly specified: Intended for individuals with CRPC and symptomatic bone metastases who have no known visceral metastatic disease; aligns with FDA approval and NCCN Category 1 recommendation. Specific numbered line (first-line versus later-line) is not explicitly defined in this policy and depends on prior therapies and clinical context.

variable

Variable sequencing: Radium-223 is a treatment option for symptomatic bone metastases in metastatic CRPC; NICE recommends use after docetaxel or when docetaxel is contraindicated or unsuitable. NCCN lists radium-223 as Category 1 for symptomatic bone metastases, so the exact sequencing (first-line versus later-line) may vary based on prior therapies and clinical judgment.

Consider prior exposure to docetaxel and other systemic therapies when selecting treatment sequencing.

primarily indicated in CRPC after progression to metastatic disease with symptomatic bone mets per ALSYMPCA trial and guidelines

Clinical Background & Evidence

Radium‑223 (Radium Ra 223 dichloride, Xofigo®) is an alpha‑emitting radiopharmaceutical that mimics calcium and selectively localizes to areas of increased bone turnover by binding to hydroxyapatite. It delivers short‑range, high‑energy alpha radiation to tumor‑involved bone, thereby targeting skeletal metastases while limiting exposure to surrounding tissues. Radium‑223 is FDA‑approved for treatment of castration‑resistant prostate cancer with symptomatic bone metastases and no known visceral metastatic disease; pivotal trials demonstrated improved overall survival compared with placebo.

Evidence, Trials and Guideline Citations

Radium-223 (Xofigo) — evidence and product labeling

Pivotal trial evidenceALSYMPCA (Parker et al., NEJM 2013) demonstrated survival benefit for radium-223 in metastatic CRPC with symptomatic bone metastases

Product labeling supportFDA prescribing information (Xofigo PI, revised May 2013) provides dosing, hematologic monitoring, and safety details supporting use

Coverage alignmentPolicy coverage and recommended regimen reflect ALSYMPCA trial findings and product labeling (6 injections at 4-week intervals)

Guideline and trial references — key citations

NCCNNCCN Drugs and Biologics Compendium: recommends radium-223 for symptomatic bone metastases without visceral disease (Category 1)

AUA/SUO

Policy History & Review

2025-09annual_reviewLatest

Policy reviewed and renewed during the September 2025 annual review.

2024-09annual_review

Policy revised following the September 2024 annual review.

2023-09annual_review

Policy Summary

PayerBlue Cross Blue Shield - South Dakota

PolicyRadium Ra 223 Dichloride (Xofigo) — coverage criteria

Policy CodePolicy N/A

Change TypeAnnual review / renewal (no material change)

Effective DateSep 1, 2017

Last ReviewSep 1, 2025

Next Review DateN/A

SourceLink

On This Page

Billing Rule

Code reporting and policy review

Report radium-223 services using appropriate coding on claims. The HCPCS code A9606 (Radium RA-223 dichloride, therapeutic, per microcurie) should be used for the drug. Include relevant CPT/HCPCS, ICD-10 diagnosis codes supporting CRPC with bone metastases, and appropriate revenue codes/places of service. This policy is reviewed annually.

HCPCS: A9606 — Radium RA-223 dichloride, therapeutic per microcurie.
Include ICD-10 diagnosis codes that reflect metastatic castration‑resistant prostate cancer with bone metastases.
Use appropriate revenue codes and outpatient place of service when applicable.
Policy reviewed annually (see Policy History).

Denial Risk

Coverage triggers and denials

Coverage will be denied when medical necessity criteria are not met, or when excluded conditions apply. Common reasons for denial include known visceral metastases, lymphadenopathy >3 cm, prior course of radium-223, treatment beyond six injections, or concurrent use with chemotherapy/biologic therapy.

Denial triggers: Known visceral metastatic disease or lymphadenopathy >3 cm.
Denial triggers: Prior receipt of a complete course of radium-223 or requests for >6 injections.
Denial triggers: Concurrent chemotherapy or biologic therapy (outside clinical trials).
Denial triggers: Failure to provide required documentation demonstrating symptomatic bone metastases and recent imaging.

Note

Docetaxel consideration

NICE and some guideline language note prior treatment with docetaxel (or docetaxel contraindicated/unsuitable) as part of clinical sequencing for radium-223 in certain health systems. This policy does not impose a formal step therapy requirement but acknowledges docetaxel may be considered per NICE guidance and clinical judgment.

Docetaxel consideration: NICE recommends radium-223 for patients who have had docetaxel, or when docetaxel is contraindicated or unsuitable.
This policy: No formal step therapy requirement is specified.
Clinical sequencing should follow specialty guidelines (NCCN, AUA/SUO) and treating clinician judgment.

Denial Risk

Visceral disease exclusion

Concomitant visceral disease is an exclusion. Therapies will not be authorized or will be denied if imaging demonstrates known visceral metastatic disease or lymphadenopathy exceeding guideline-specified thresholds.

Visceral disease exclusion: No evidence of visceral metastases on imaging within 30 days is required for coverage.
Lymphadenopathy >3 cm (per AUA/SUO) is a contraindication to radium-223 per guideline recommendations.

Billing Rule

Required coding on claims

Required coding on claims: use HCPCS A9606 for radium-223 and include supporting diagnosis codes indicating castration‑resistant prostate cancer with symptomatic bone metastases. Ensure claims include appropriate CPT/HCPCS, revenue codes, place of service, and ICD-10 codes to reflect medical necessity; missing or incorrect coding may result in denial.

HCPCS: A9606 — Radium RA-223 dichloride, therapeutic per microcurie.
Include ICD-10 codes supporting metastatic prostate cancer with bone involvement and documentation of castration‑resistant status when available.
Ensure revenue codes and outpatient place of service are included where applicable.
Claims missing A9606 or appropriate diagnosis coding risk denial.

Step Therapy

Step therapy not stated here

Step therapy: this policy does not establish a step therapy requirement for radium-223. Clinical sequencing and prior treatments (such as docetaxel) may be considered according to guidelines but are not enforced as mandatory steps in this policy.

No step therapy requirement specified in this policy.
Clinicians should follow guideline-based sequencing and document rationale when prior therapies influence treatment choice.

Documentation Required

Required clinical documentation

Required clinical documentation must be provided to support authorization and claims: evidence of symptomatic skeletal metastases, recent imaging showing absence of visceral metastases (≤30 days), serum testosterone demonstrating castrate level (<50 ng/dL), and baseline and ongoing hematologic labs per label (ANC, platelets, hemoglobin).

Documentation: symptomatic bone metastases and imaging (CT, MRI, bone scan) within 30 days showing no visceral disease.
Documentation: serum testosterone <50 ng/dL to confirm castrate status; record of ongoing ADT if applicable.
Baseline labs prior to first dose: ANC ≥1.5 x10^9/L, platelets ≥100 x10^9/L, hemoglobin ≥10 g/dL.
Prior to subsequent doses: ANC ≥1.0 x10^9/L and platelets ≥50 x10^9/L.
Discontinue or deny if documentation shows prior full course of radium-223 or request exceeds 6 injections.

Baseline hemoglobinHemoglobin ≥ 10 g/dL prior to the first radium-223 dose

Subsequent-dose ANCANC ≥ 1.0 x 10^9/L prior to subsequent doses

Subsequent-dose plateletsPlatelets ≥ 50 x 10^9/L prior to subsequent doses

Treatment discontinuation criterionDiscontinue if counts do not recover within 6–8 weeks after last administration despite supportive care

Brand nameXofigo® is the marketed product name for radium-223 dichloride

Definition — CRPC with bone mets

Disease conceptCRPC with bone mets refers to prostate cancer that progresses despite androgen-deprivation therapy (castration-resistant) and presents with skeletal metastases

Clinical contextTypically occurs while patient remains on ADT or after progression despite prior hormonal therapy

Implication for therapyIndicates candidate population for radium-223 when no known visceral metastases are present

Definition — Radium-223 (Xofigo) bone-seeking radiopharmaceutical

Bone-seeking radiopharmaceuticalRadium-223 (Xofigo) is a bone-seeking radiopharmaceutical that delivers alpha radiation to skeletal metastases

Therapeutic intentUsed therapeutically to target tumor-involved bone while minimizing exposure to surrounding tissues

Product identityRadium Ra 223 dichloride (Xofigo) references the same bone-seeking agent in product labeling and literature

Primary indication: Primarily indicated for castration-resistant prostate cancer with symptomatic bone metastases and no known visceral metastatic disease, consistent with the ALSYMPCA trial and guideline recommendations (NCCN, AUA/SUO).

AUA/SUO guideline (2023) cited as supporting use for symptomatic bone metastases in CRPC

NICE and ALSYMPCANICE guidance (2016) and ALSYMPCA trial (NEJM 2013) are cited as key references informing policy and clinical context

Policy revised following the September 2023 annual review.

2022-09annual_review

Policy revised following the September 2022 annual review.

2021-09annual_review

Policy renewed following the September 2021 annual review.

2020-09annual_review

Policy renewed following the September 2020 annual review.

2019-09annual_review

Policy renewed following the September 2019 annual review.

2018-09annual_review

Policy revised following the September 2018 annual review.

2017-09establishment

Policy created (New Policy) in September 2017.