ModifiedPremera BluecrossPolicy 6.01.525

Therapeutic Radiopharmaceuticals in Oncology

Defines medical necessity, documentation, dosing, and limits for specific therapeutic radiopharmaceuticals (Lutathera, Pluvicto, Xofigo) and describes required provider documentation for authorization.

Policy Summary

PayerPremera Bluecross

PolicyTherapeutic Radiopharmaceuticals in Oncology

Policy CodePolicy 6.01.525

Change TypeMaterial updates to indications, performance status equivalency, and Pluvicto eligibility

Effective Date

Next Review Date

Key ActionObtain prior authorization with documentation of receptor-positive imaging, prior therapies when required, and confirmation of adequate organ function.

SourceLink

POLICY UPDATE CHANGES

FDA expanded approval of Lutathera (lutetium 177 dotatate) to pediatric individuals 12 years and older.

Added ECOG Performance Status score of 2 or less as equivalent to Karnofsky score ≥60.

Updated Pluvicto (lutetium Lu 177 vipivotide tetraxetan) coverage criteria to include treatment of certain individuals who have not received prior taxane-based chemotherapy.

3radiopharmaceuticals addressed

4max Lutathera doses

6max Pluvicto doses

Category 1

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NCCN recommendation for Lu-177-PSMA-617

ECOG ≤2performance status equivalency

Coverage Criteria

Initial therapy — Lutathera

Lutathera is considered medically necessary when ALL of the following are met:

Age: Patient aged >= 12 years>=12 years

Documented FDA expansion to pediatric individuals 12 years and older supports this age criterion.

Tumor grade and type: Documented low- or intermediate-grade (Ki-67 <= 20%) locally advanced or metastatic gastroenteropancreatic neuroendocrine tumor (foregut, midgut, or hindgut)Ki-67 <=20%

Policy and NCCN-aligned eligibility require well-differentiated NETs.

Receptor expression: Somatostatin receptor expression confirmed by SSTR-based imaging (68Ga-dotatate/68Ga-Dotatoc or 64Cu-Dotatate PET, or somatostatin receptor scintigraphy) with uptake greater than liverSSTR uptake > liver

Preferred PET tracers listed in policy.

Progression on SSA: Documented disease progression while on long-acting somatostatin analog therapy (octreotide LAR or lanreotide) as shown on CT or SSTR-PET

Progression while on SSA is required prior to PRRT initiation.

SSA washout and timing: Not receiving long-acting somatostatin analogues for at least 4 weeks prior to initiation; short-acting octreotide discontinued at least 24 hours before first dose; long-acting octreotide 30 mg IM may be given 4–24 hours after each Lutathera dose

Operational dosing timing recommended to avoid receptor competition.

Renal function: No severe renal impairment: creatinine clearance >= 40 mL/min>=40 mL/min

Cockcroft-Gault calculation with actual body weight referenced for discontinuation thresholds.

Hematologic and hepatic function: Adequate bone marrow and hepatic function as determined by the treating physician

Policy requires assessment of marrow and liver function prior to treatment.

Performance status: Karnofsky Performance Status >= 60 or equivalent ECOG <= 2

ECOG <=2 accepted as equivalent to Karnofsky >=60 per policy history.

Initial therapy — Pluvicto

Pluvicto is considered medically necessary when ALL of the following are met:

Age: Patient is an adult (>=18 years)>=18 years

Policy states Pluvicto is for adults with PSMA-positive mCRPC.

Diagnosis: Metastatic castration-resistant prostate cancer (mCRPC)

Indication aligned with FDA approval and policy statements.

PSMA status: PSMA-positive disease demonstrated by Ga-68 PSMA-11 or F-18 piflufolastat PET

Corresponding diagnostic agents (Locametz/Illuccix, Pylarify) are listed for PET selection.

Prior therapy:

Initial therapy — Xofigo

Xofigo is considered medically necessary when ALL of the following are met:

Age: Patient is an adult (>=19 years)>=19 years

Policy lists adults 19 years or older for Xofigo eligibility.

Diagnosis: Castration-resistant prostate cancer with symptomatic bone metastases and no known visceral metastatic disease (e.g., lungs, liver, large lymph nodes)

Xofigo indication requires symptomatic bone mets without visceral disease.

Lu-177-PSMA-617 (Pluvicto) — coverage criteria

Covered when ALL of the following are met

Pluvicto indication and administration: Adult with PSMA-positive metastatic castration-resistant prostate cancer who meets prior-therapy requirements; therapy administered by physicians qualified in radiopharmaceutical use; follow recommended dosing of 7.4 GBq (200 mCi) every 6 weeks for up to 6 doses; individuals should be well-hydrated during treatment; refer to prescribing information for dose modifications and discontinuation criteria.7.4 GBq (200 mCi) every 6 weeks; up to 6 doses

Dose may be reduced once by 20% to 5.9 GBq (160 mCi); dosing interval may be extended to up to 10 weeks for treatment interruptions; permanent discontinuation criteria and toxicity-based stopping rules are specified in prescribing guidance.

Lutetium-177 dotatate (Lutathera) — coverage criteria

Covered when ALL of the following are met

Lutetium-177 dotatate indication: Radiolabeled somatostatin analogue therapy for somatostatin receptor–positive neuroendocrine tumors (peptide receptor radionuclide therapy) administered by physicians qualified in radiopharmaceutical use per product guidance.

Policy references use for somatostatin receptor–positive NETs with documented receptor expression and treatment per product dosing schedule (7.4 GBq every 8 weeks for a total of 4 doses).

Covered Indications aligned with evidence and guidelines

Covered when criteria and guideline-aligned indications are met

Lu-177-dotatate for gastroenteropancreatic NET: Individuals with treatment-refractory gastroenteropancreatic neuroendocrine tumors who meet somatostatin receptor–positive imaging and adequate organ function criteria; randomized trial evidence demonstrates improved response rate, progression-free survival, and overall survival with Lu-177-dotatate compared to long-acting octreotide.Requires somatostatin receptor–positive tumor on imaging and adequate bone marrow, renal, and hepatic function

Supported by randomized controlled trial evidence and NCCN guideline eligibility criteria.

Lu-177-dotatate for other NETs: Use in bronchopulmonary/thymic NETs and select rare NETs (including consideration for pheochromocytoma/paraganglioma) may be considered in select circumstances; evidence is less robust and NCCN/other guidance encourage clinical trial enrollment or cautious use for rare NETs.Somatostatin receptor–positive imaging recommended

Evidence for non-gastroenteropancreatic NETs is limited and often derived from retrospective data.

Agent-specific coverage

Coverage is agent- and indication-specific and requires meeting FDA-labeled indications, applicable guideline-supported criteria, and documented performance status.

Lutathera (Lu-177 DOTATATE) coverage: Covered for somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors in adults and pediatric individuals 12 years and older per FDA approval when policy clinical criteria (including performance status and organ function) are met.FDA indication and documented performance status

Policy references FDA approval (including pediatric expansion), NCCN eligibility, and product dosing guidance.

Pluvicto (Lu-177-PSMA-617) coverage: Covered for adult individuals with PSMA-positive metastatic castration-resistant prostate cancer who meet policy criteria; coverage criteria were updated to allow certain individuals who have not received prior taxane-based chemotherapy in select circumstances when policy criteria are satisfied.FDA indication and policy-specific eligibility

Policy emphasizes prior AR-pathway inhibition and taxane chemotherapy historically but allows documented reasons to delay taxane or recent exceptions per policy history updates.

Use of therapeutic radiopharmaceuticals beyond the total dose limits specified in this policy is considered investigational. Specifically, Lutathera (lutetium-177 dotatate) given greater than a total of 4 doses, Pluvicto (lutetium Lu‑177 vipivotide tetraxetan) given greater than a total of 6 doses (administered once every 6 weeks), and Xofigo (radium‑223 dichloride) given greater than a total of 6 doses are investigational and do not meet coverage criteria. The policy also states that Lutathera is investigational for indications not meeting the policy’s Lutathera criteria, including pheochromocytoma and paraganglioma when those Lutathera-specific criteria are not satisfied.

Before approval of lobenguane I‑131, lutetium‑177 dotatate was used off‑label to treat pheochromocytoma and paraganglioma in some patients. Available evidence in this population is limited and consists mainly of case series, registries, and single‑arm studies; as a result, off‑label Lu‑177‑dotatate use for these indications is considered investigational unless it meets specific policy criteria or is within an FDA‑labeled indication.

Guideline and consensus statements provide limited support for Lu‑177‑dotatate in certain rare neuroendocrine tumor (NET) subtypes. NCCN lists consideration of Lu‑177‑dotatate for select bronchopulmonary/thymic NETs and for unresectable or metastatic pheochromocytoma/paraganglioma with somatostatin receptor positivity but notes data are limited and encourages clinical trial participation. Similarly, the North American Neuroendocrine Tumor Society suggests restricting Lu‑177‑dotatate use in pheochromocytoma/paraganglioma to clinical trials or select cases due to limited evidence.

Diagnostic-only radiopharmaceuticals and products withdrawn from commercial supply are not therapeutic options addressed by this policy. For example, iobenguane 123 (AdreView) is a diagnostic agent and is not a therapeutic treatment. AZEDRA (iobenguane 131), although FDA‑approved for certain pheochromocytoma/paraganglioma indications, had manufacturer production discontinued in August 2023 and is not further addressed as an active therapeutic option in this policy.

Treatments and indications that do not meet the policy’s specified coverage criteria are considered investigational and not medically necessary. This includes any use that exceeds the policy’s stated total dose limits (e.g., >4 total Lutathera doses; >6 total Pluvicto doses; >6 total Xofigo doses) as well as uses outside the agent‑specific criteria outlined in the policy.

The use of lutetium‑177 dotatate for pheochromocytoma and paraganglioma remains off‑label in many cases and is supported by limited and low‑quality evidence (systematic reviews of single‑arm studies, registries, and case series). The policy therefore treats Lu‑177‑dotatate for these indications as investigational or not medically necessary unless specific criteria or supporting evidence consistent with policy requirements are documented.

Overall evidence for some uses of Lu‑177‑dotatate outside gastroenteropancreatic NETs is insufficient to determine net health benefit. Meta‑analyses and small series report response rates in pheochromocytoma/paraganglioma but lack randomized comparative data; guideline groups therefore recommend caution and often limit routine use to clinical trials or selected cases.

Lutathera coverage is limited to somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors (foregut, midgut, hindgut) and to patients meeting the policy’s clinical eligibility criteria, including documented somatostatin receptor positivity, appropriate performance status, and adequate organ function. Uses of Lutathera for other tumor types or indications not meeting FDA labeling and the policy’s clinical criteria (for example, routine treatment of pheochromocytoma/paraganglioma outside trial settings) are not covered.

Coding and Dosing

Covered HCPCS CodesHCPCSCovered

A9513	Lutetium lu 177, dotatate; therapeutic; mCi (Lutathera)
A9606	Radium RA-223 dichloride, therapeutic; per UCI (Xofigo)
A9607	Lutetium lu 177 vipivotide tetraxetan, therapeutic, mCi (Pluvicto)

Referenced agents (no billing codes listed in this section)mixed

No codes listed

Therapeutic radiopharmaceutical agents mentionedmixed

Lu-177-PSMA-617	lutetium Lu 177 vipivotide tetraxetan therapeutic radioligand (agent name as listed)
Lu-177-dotatate	lutetium-177 dotatate (Lutathera) therapeutic radioligand
Ra-223	radium Ra 223 (Xofigo) therapeutic radiopharmaceutical

Policy-related HCPCS codes (historical additions/removals)HCPCS

A9590	HCPCS code previously added (specific descriptor not provided in excerpt)
A9593	HCPCS code previously added (specific descriptor not provided in excerpt)
A9594	HCPCS code previously added (specific descriptor not provided in excerpt)
A9595	HCPCS code previously added (specific descriptor not provided in excerpt)
A9596	HCPCS code previously added (specific descriptor not provided in excerpt)
A9606	HCPCS code previously added (specific descriptor not provided in excerpt)
A9607	HCPCS code previously added (specific descriptor not provided in excerpt)
A9800	HCPCS code previously added (specific descriptor not provided in excerpt)
A9699	HCPCS code removed in a prior update

inv-20: Dosing schedule — Lutathera and Pluvicto

Lutathera per-dose activity7.4 GBq (200 mCi) per administration

Lutathera dosing intervalEvery 8 weeks

Lutathera total administrations allowedTotal of 4 doses

Pluvicto per-dose activity7.4 GBq (200 mCi) per administration

Pluvicto dosing intervalEvery 6 weeks (see Pluvicto block for allowable extension)

inv-21: Pluvicto dosing interval

Provider Actions and Authorization

Prior Authorization

Prior Authorization Required

Prior authorization is required for Lutathera, Pluvicto (Lu-177-PSMA-617), and Xofigo. Approvals are limited to durations and total dose counts consistent with the policy and FDA prescribing information; requests exceeding dose limits will be considered investigational / not medically necessary.

Initial and non‑formulary exception approvals may be issued for up to 12 months.
Dose limits: Lutathera — up to 4 total doses; Pluvicto — up to 6 total doses (administered once every 6 weeks); Xofigo — up to 6 total doses (typically every 4 weeks).
Requests for treatment greater than the specified total doses are investigational / not medically necessary.

Prior Authorization

Prior Authorization and Indication Note

These radiopharmaceutical therapies are specialized and require coordination of diagnostic PSMA or somatostatin receptor imaging, prior systemic therapies where applicable, and documentation of organ function and performance status. Prior authorization requests should reference the specific indication and supporting diagnostic imaging used to select patients (e.g., Ga‑68 PSMA‑11 or F‑18 piflufolastat for Pluvicto; 68Ga-/64Cu‑dotatate or somatostatin receptor scintigraphy for Lutathera).

Background

Therapeutic radiopharmaceuticals deliver targeted radiation by combining a radionuclide with a tumor‑directing molecule. Examples addressed in this policy include Lutathera (lutetium‑177 dotatate) for somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors, Pluvicto (lutetium‑177 PSMA‑617) for PSMA‑positive metastatic castration‑resistant prostate cancer, and Xofigo (radium‑223) for symptomatic bone‑predominant castration‑resistant prostate cancer. These agents require specialist oversight (e.g., nuclear medicine or radiation oncology), targeted imaging to confirm receptor expression, and adherence to agent‑specific dosing and safety criteria.

Definitions

inv-42: SSTR-positive definition

DefinitionSSTR-positive: Uptake on somatostatin receptor (SSTR) PET in measurable lesions greater than liver uptake

Preferred imaging modalitiesSSTR-PET radiotracers: Ga-68 dotatate, Ga-68 dotatoc, or Cu-64 dotatate; SPECT only if PET unavailable

Use caseRequired to confirm eligibility for Lu-177-dotatate (Lutathera) therapy

inv-43: PSMA-positive definition

DefinitionPSMA-positive: Demonstrated by PSMA PET imaging (e.g., Ga-68 PSMA-11/Locametz or F-18 piflufolastat/Pylarify)

Use caseRequired to select individuals for Lu-177-PSMA-617 (Pluvicto) therapy

Policy Summary

PayerPremera Bluecross

PolicyTherapeutic Radiopharmaceuticals in Oncology

Policy CodePolicy 6.01.525

Change TypeMaterial updates to indications, performance status equivalency, and Pluvicto eligibility

Effective Date

Next Review Date

Key ActionObtain prior authorization with documentation of receptor-positive imaging, prior therapies when required, and confirmation of adequate organ function.

SourceLink

On This Page

Previously treated with an androgen receptor (AR) pathway inhibitor and a taxane-based chemotherapy OR a documented reason to delay taxane chemotherapy

Policy requires prior AR-pathway inhibition and taxane chemotherapy unless appropriateness to delay taxane is documented; recent updates allow certain exceptions.

Lu-177-PSMA-617 for PSMA-positive mCRPC: Individuals with PSMA-positive metastatic castration-resistant prostate cancer who have progressed on AR-directed therapy and taxane chemotherapy have demonstrated improved overall survival and radiographic PFS with Lu-177-PSMA-617 plus SOC versus SOC alone; ensure appropriate PSMA PET imaging and absence of dominant PSMA-negative lesions.PSMA-positive lesions on appropriate PET imaging; prior therapies per guideline when applicable

NCCN provides a category 1 recommendation for selected patients; monitor for increased Grade 3+ adverse events.

Radium-223 for symptomatic bone metastases in CRPC: Radium-223 is indicated for castration-resistant prostate cancer with symptomatic bone metastases without known visceral disease and is administered per standard dosing by experienced physicians.Symptomatic bone metastases without visceral metastatic disease

Approved agent with defined dosing schedule (50 kBq/kg IV every 4 weeks for a total of 6 injections).

AZEDRA (iobenguane 131) and diagnostic agents: Although AZEDRA had FDA approval for certain pheochromocytoma/paraganglioma, manufacturer discontinued production and AZEDRA and diagnostic-only agents (e.g., iobenguane 123) are not addressed as active treatment coverage in this policy excerpt.N/A

Operational note: withdrawn production limits policy focus for AZEDRA.

Standard Pluvicto intervalEvery 6 weeks

Allowed interruption extensionDosing interval may be extended up to every 10 weeks for temporary dose interruptions

Hydration noteIndividuals should be well-hydrated during treatment per prescribing information

inv-22: Maximum Pluvicto administrations

Maximum number of Pluvicto dosesUp to 6 doses

Allowed single dose reductionMay be reduced once by 20% to 5.9 GBq (160 mCi); dose should not be re-escalated

Discontinuation triggersPermanent discontinuation for specified recurrent Grade 3+ toxicities or other severe adverse events per prescribing information

inv-23: radium-223 dosing schedule

Radium-223 dose50 kBq/kg (1.35 microcurie/kg) IV per administration

Radium-223 dosing intervalEvery 4 weeks

Radium-223 total administrationsTotal of 6 injections

inv-24: Performance status (Karnofsky >=60 or ECOG <=2)

Karnofsky thresholdKarnofsky Performance Status score of 60 or greater

ECOG equivalencyECOG Performance Status score of 2 or less is accepted as equivalent

Documentation requirementPerformance status must be documented in the medical record prior to treatment

Pluvicto requires demonstration of PSMA‑positive disease by an approved PET agent (e.g., Locametz, Illuccix, Pylarify).
Lutathera requires somatostatin receptor expression confirmed by receptor‑based imaging (68Ga‑dotatate, 64Cu‑Dotatate, 68Ga‑Dotatoc PET or somatostatin receptor scintigraphy).
Prior systemic therapy requirements for Pluvicto: previous treatment with an androgen‑receptor (AR) pathway inhibitor and a taxane‑based chemotherapy (or documentation that deferring taxane chemotherapy is appropriate).

Documentation Required

Imaging, Prior Therapy, and Organ Function Documentation

Documentation expectations for prior authorization include diagnostic imaging reports confirming target receptor expression, records of prior therapies received, and laboratory/organ function results demonstrating adequate marrow, renal, and hepatic function. Absence of required imaging or prior therapy documentation may result in denial.

Imaging: PET/CT reports showing PSMA‑positive or somatostatin receptor–positive lesions as appropriate.
Prior therapy: medical records confirming prior AR pathway inhibitor and taxane chemotherapy for Pluvicto (or clinical justification to delay taxane).
Organ function: recent creatinine clearance (Cockcroft‑Gault), complete blood count, liver function tests, and performance status (Karnofsky ≥60 or ECOG ≤2).
Adverse event history: documentation showing no recurrent Grade 3–4 hematologic or nonhematologic toxicities that would preclude retreatment.

Billing Rule

Prior Authorization and HCPCS Coding

Billing and coding must use the appropriate HCPCS codes for the specific radiopharmaceutical when submitting authorization or claims. Use up‑to‑date HCPCS coding consistent with the policy history and payer updates.

HCPCS: A9513 — Lutetium Lu‑177 dotatate (Lutathera).
A9607 — Lutetium Lu‑177 vipivotide tetraxetan (Pluvicto).
A9606 — Radium Ra‑223 dichloride (Xofigo).
Verify current HCPCS codes at the time of claim submission; codes have changed over prior updates and removals.

Denial Risk

Dose Limits Trigger Noncoverage

Dose limits described in the policy are enforced. Requests for dosing beyond the FDA‑recommended total number of administrations will be considered investigational and are not covered.

Lutathera: recommended 7.4 GBq (200 mCi) every 8 weeks for total of 4 doses; >4 doses = investigational.
Pluvicto: recommended 7.4 GBq (200 mCi) every 6 weeks for up to 6 doses; >6 doses = investigational.
Xofigo: typically given every 4 weeks for up to 6 doses; >6 doses = investigational.

Denial Risk

Triggers for Permanent Discontinuation of Lu‑177 Therapies

Specific triggers require permanent discontinuation of therapy with Lu‑177 agents. Authorization and clinical management should reflect these safety stop rules from the prescribing information.

Lu‑177 dotatate (Lutathera): permanently discontinue for hepatotoxicity (bilirubin >3× ULN) or hypoalbuminemia <30 g/L with prothrombin ratio <70%, or renal toxicity defined as creatinine clearance <40 mL/min (Cockcroft‑Gault).
Lu‑177‑PSMA‑617 (Pluvicto): permanently discontinue for recurrent Grade ≥3 myelosuppression after one dose reduction; Grade ≥3 renal toxicity; recurrent renal toxicity after one dose reduction; recurrent Grade 3 dry mouth after one dose reduction; recurrent Grade ≥3 gastrointestinal toxicity after one dose reduction; AST/ALT >5× ULN in absence of liver metastases; any unacceptable or serious adverse reaction requiring >4 weeks treatment delay; recurrent Grade 3–4 or persistent/intolerable Grade 2 adverse reaction after one dose reduction.

Documentation Required

Required Documentation for Initial Treatment

Initial treatment authorization must be supported by specified clinical documents. For continuation or reauthorization, provide interval imaging, toxicity assessments, and justification for further dosing within policy limits.

Initial documentation: history & physical supporting diagnosis, pathology verification, and receptor‑based imaging confirming target expression.
Laboratories: creatinine clearance, CBC demonstrating adequate marrow reserve, and liver function tests prior to initiation.
Performance status: documented Karnofsky ≥60 or ECOG ≤2.
For reauthorization: evidence of clinical benefit or stability, absence of disqualifying toxicities, and adherence to dose and interval limits.

Documentation Required

Administration and Documentation Expectations

Administration and dosing should follow the FDA prescribing information and established procedural steps for radiopharmaceuticals. Dose modifications, interruptions, or permanent discontinuation should follow guidance for adverse reactions and documented in the medical record.

Lutathera: withhold long‑acting somatostatin analogues 4–6 weeks prior to each dose; stop short‑acting agents 24 hours prior and resume 4–24 hours after treatment.
Pluvicto: individuals should be well‑hydrated; dose may be reduced once by 20% (to 5.9 GBq / 160 mCi) and should not be re‑escalated; dosing interval may be extended up to every 10 weeks for toxicity management.
Radiopharmaceuticals must be used by or under supervision of physicians qualified in safe handling and administration of radiopharmaceuticals and within a quality management program.

Documentation Required

Required Clinical Documentation

Required clinical documentation to support medical necessity includes pathology confirmation, imaging of target receptor expression, prior therapy verification, organ function tests, and performance status.

Pathology report confirming diagnosis and tumor grade (e.g., Ki‑67 ≤20% for neuroendocrine tumors).
Imaging reports: somatostatin receptor PET for Lutathera; PSMA PET for Pluvicto.
Medical records verifying prior AR pathway inhibitor and taxane chemotherapy for Pluvicto (or clinical rationale for deferring taxane).
Recent labs: CBC, creatinine clearance (Cockcroft‑Gault), LFTs; documentation of no prohibitive toxicities (see safety criteria).

Note

Prescribing Information and Exception Durations

Policy follows FDA dosing and administration prescribing information. Non‑formulary exception authorizations may be approved up to 12 months consistent with policy history; any exception durations shorter or longer than standard prescribing intervals should be justified in the record.

Approvals (including non‑formulary exception reviews) may be issued up to 12 months.
Follow prescribing information for dosing schedules and recommended dose modifications.
Document any deviations and clinical rationale when requesting exceptions to standard dosing or duration.

Step Therapy

Step Therapy Context and Therapy Sequencing

Step therapy context and typical sequencing: these radiopharmaceuticals are generally used after specified prior systemic therapies and occupy a later line of treatment for mCRPC and neuroendocrine tumors per guideline recommendations.

For mCRPC, Pluvicto is typically used after progression on androgen‑receptor pathway inhibitors and taxane chemotherapy (per NCCN and clinical trial eligibility).
For neuroendocrine tumors, Lutathera is used for somatostatin receptor–positive, progressive disease after somatostatin analogue therapy.
No specific step‑therapy program is specified in this excerpt, but clinical sequencing expectations should be documented in the authorization request.

Note

Medicare Coverage Gap

Medicare coverage gap: there is currently no Medicare National Coverage Determination (NCD) for these therapies; this policy does not by itself establish Medicare coverage. Providers should verify local Medicare administrative contractor (MAC) determinations and payer‑specific requirements.

No national coverage determination exists for these agents.
This policy does not establish Medicare coverage; check MAC or local coverage articles for Medicare billing and coverage guidance.

Gallium Ga-68 PSMA-11 (Locametz, Illuccix) or piflufolastat F-18 (Pylarify)

inv-44: PRRT definition

DefinitionPeptide receptor radionuclide therapy (PRRT): Therapy using radiolabeled peptides (e.g., lutetium-177 dotatate) that bind somatostatin receptors, are internalized, and deliver radiation to induce tumor cell damage

Example agentLutetium-177 dotatate (Lutathera) is a PRRT agent for somatostatin receptor–positive NETs

Administration contextDelivered by physicians qualified in radiopharmaceutical use and handling per product guidance

inv-45: Lu-177-PSMA-617 (Pluvicto) definition

Agent nameLu-177-PSMA-617 (Pluvicto) — lutetium Lu 177 vipivotide tetraxetan

MechanismPSMA-targeted radioligand: PSMA-617 ligand delivers lutetium-177 to PSMA-expressing prostate cancer cells to emit beta radiation and induce DNA damage

Indication summaryFDA-approved for adult PSMA-positive metastatic castration-resistant prostate cancer (historically after AR-pathway inhibition and taxane chemotherapy)

inv-46: PSMA acronym definition

Acronym expansionPSMA = Prostate-Specific Membrane Antigen

Biologic roleA transmembrane glutamate carboxypeptidase highly expressed on prostate cancer cells and used as a target for imaging and radioligand therapy

Clinical relevanceHigh PSMA expression helps select patients for PSMA-targeted therapies like Lu-177-PSMA-617

inv-47: Lu-177-PSMA-617 brief description

CompositionLu-177-PSMA-617 (vipivotide tetraxetan) combines the PSMA-617 ligand with lutetium-177 radioactive component

ActionBinds PSMA-expressing cells and delivers beta-minus radiation causing DNA damage to tumor cells and nearby cells

Selection criteriaIndividuals should be selected using PSMA PET imaging (e.g., Ga-68 gozetotide or approved PSMA-11/F-18 agents)

inv-48: Lu-177-dotatate description

Agent nameLutetium-177 dotatate (Lutathera)

MechanismRadiolabeled somatostatin analogue that binds somatostatin receptor–expressing tumor cells, internalizes, and delivers beta radiation to induce cellular damage

Indication summaryFDA-approved for somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors; dosing 7.4 GBq (200 mCi) every 8 weeks for 4 doses

inv-49: Radium-223 (Xofigo) description

Agent nameRadium-223 (Xofigo)

MechanismAlpha-emitting radiopharmaceutical that delivers alpha radiation to bone metastases with limited surrounding tissue damage

Indication and dosingFor castration-resistant prostate cancer with symptomatic bone metastases and no known visceral disease; 50 kBq/kg IV every 4 weeks for 6 injections

inv-50: Lutathera definition

Agent nameLutathera (lutetium 177 dotatate)

FDA statusApproved for somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors in adults; FDA approval expanded to pediatric individuals 12 years and older (April 23, 2024)

Clinical requirementsRequires documented somatostatin receptor positivity on SSTR imaging and adequate organ function per policy

inv-51: Pluvicto definition

Agent namePluvicto (lutetium Lu 177 vipivotide tetraxetan)

FDA statusApproved March 23, 2022 for adult individuals with PSMA-positive mCRPC who have been treated with AR-pathway inhibition and taxane chemotherapy

Dosing summaryRecommended dosing: 7.4 GBq (200 mCi) every 6 weeks for up to 6 doses; dose reduction and discontinuation rules per prescribing information

inv-52: AZEDRA definition and market status

Agent nameAZEDRA (iobenguane 131)

Regulatory statusFDA-approved for certain pheochromocytoma/paraganglioma patients (approval July 30, 2018) but manufacturer discontinued production in August 2023; not further addressed in policy

Clinical implicationProduction discontinuation removes active policy treatment focus for the agent; diagnostic iobenguane 123 (AdreView) is not therapeutic