Prostate Cancer: Imaging and Therapy Options from an Oncology Perspective

Authored By: Juliet Roldan, MBA, CNMT, RT(CT)ARRT

Prostate cancer is the most common noncutaneous malignancy among men in the United States. Accurate staging, restaging and therapy sequencing are essential to optimize outcomes across disease states.

Advanced imaging and theranostic approaches have rapidly migrated from academic centers into community oncology due to expanded U.S. Food and Drug Administration (FDA) approvals, improved tracer distribution and standardized guidance.^1,2 This review summarizes prostate-specific membrane antigen (PSMA)‑targeted diagnostics and therapies with an emphasis on pragmatic adoption in community settings.

Imaging Modalities

Multiparametric magnetic resonance imaging (mpMRI) supports diagnosis, local staging (e.g., extracapsular
extension, seminal vesicle invasion) and treatment planning within risk‑stratified pathways.^1,2 PSMA Positron Emission Tomography (PET) complements mpMRI by improving sensitivity for nodal and distant disease, informing initial staging, recurrence evaluation and downstream therapy selection.^1,2

PET Imaging for Prostate Cancer

Two 68Ga‑PSMA‑11 kits — Illuccix® (Telix) and Locametz® (Novartis/AAA) — are FDA‑approved for preparing gallium Ga‑68 gozetotide injection to identify PSMA‑positive lesions at initial staging and in biochemical recurrence.^3,4

Gozellix® (TLX007‑CDx; 68Ga gozetotide) received FDA approval in March 2025 with U.S. launch in June 2025.^5,6 18F‑DCFPyL (Pylarify®, Lantheus) is an FDA‑approved 18F‑labeled PSMA PET agent with centralized production and broad distribution for detection of suspected metastasis or recurrence.⁷

Flotufolastat F 18 (18F‑rhPSMA‑7.3; Posluma®, Blue Earth/Bracco) received FDA approval in 2023 supported by SPOTLIGHT and LIGHTHOUSE phase 3 trials, enabling use in recurrence and initial staging.^8-10

While the science clearly supports PSMA PET as the superior imaging tool in prostate cancer, payer coverage and local availability often dictate whether a patient receives PSMA PET or defaults to conventional imaging. Particularly for initial staging, coverage policies vary. Some require evidence of high-risk features (e.g., Gleason ≥ 8, PSA > 20, or locally advanced disease) while others limit approval until after biochemical recurrence.

In practice, access is determined less by clinical evidence and more by reimbursement policy and infrastructure – a gap that directly impacts patient outcomes. Operational considerations include tracer availability and scheduling. 18F agents
(Pylarify, Posluma) offer regional distribution and scheduling flexibility, whereas 68Ga kits (Illuccix, Locametz, Gozellix) require an on‑site generator or nearby radiopharmacy for synthesis.^3-8

Radiopharmaceutical Therapy

Lutetium Lu‑177 vipivotide tetraxetan (Pluvicto®; 177Lu‑PSMA‑617) was FDA‑approved in 2022 for PSMA‑positive mCRPC after androgen receptor pathway inhibitor (ARPI) and taxane therapy and, on March 28, 2025, received an expanded indication permitting treatment after ARPI in adults appropriate to delay taxane chemotherapy.^11-12,22

Hematologic monitoring is required and sequencing relative to Ra‑223 warrants attention to marrow reserve.¹³ Radium‑223 dichloride (Xofigo®) is indicated for mCRPC with symptomatic bone metastases and no known visceral disease; dosing is every four weeks for six injections, with long‑term safety supported by post‑marketing data.^13-14

Table 1: PSMA PET agents and operational considerations

Systemic Therapies (Context for Sequencing)

Androgen‑receptor pathway inhibitors (ARPIs) and androgen‑deprivation therapy (ADT) remain foundational across disease stages. Darolutamide (Nubeqa®) carries indications for nonmetastatic CRPC and metastatic hormone‑sensitive prostate cancer (with or without docetaxel per 2025 labeling), informing sequencing before or alongside radiopharmaceuticals.¹⁵

Consistent with National Comprehensive Cancer Network (NCCN) v2.2025, ARPIs with ADT remain first‑line for metastatic hormone‑sensitive disease, while 177Lu radioligand therapy is positioned in mCRPC after ARPI and may be considered before taxane chemotherapy in appropriate patients.^11,12,22

Implementation by Oncology Practices

• Build supply pathways with regional radiopharmacies for 68Ga kits and 18F agents.^3-8
• Define PSMA PET referral triggers at diagnosis and biochemical recurrence.^1,2
• Establish a multidisciplinary team. The NCCN and Society of Nuclear Medicine and Molecular Imaging (SNMMI) both emphasize that a team-based infrastructure is not only essential for clinical excellence but also for safety, compliance, patient access and therapy utilization.
• Develop a Lu‑177 radioligand therapy workflow (eligibility, labs, radiation safety, infusion and logistics) and a separate Ra‑223 pathway for bone‑
  predominant disease and patients without visceral metastases.^11,13,22
• Align reporting and interpretation to SNMMI/EANM PSMA PET/CT standards¹ and to NCCN pathways to support payer authorization and documentation consistency.²²

Factors Determining Drug Selection

• Patient factors: Goals and preferences include survival vs. symptom control, route (oral vs. infusion), clinic time and quality‑of‑life impact.²
• Comorbidities and risks — cardiovascular disease, diabetes/obesity, osteoporosis, seizure risk, thromboembolism — guide agent selection and monitoring.²
• Organ function and labs (renal/hepatic
  function, marrow reserve, QTc, electrolytes)
  and performance status affect eligibility for radioligand therapy and systemic agents.^11,13
• Concomitant medications and interactions (e.g., CYP3A4/P‑gp) should be reviewed when selecting ARPIs; reproductive considerations and adherence supports may modify choices.¹⁵
• Disease factors:
• Stage and phenotype — hormone‑sensitive vs. castration‑resistant, visceral vs. bone‑predominant disease, symptom burden — shape therapy sequencing.²
• Biomarkers such as PSMA positivity
  determine eligibility for Lu‑177 therapy; MSI‑H or DDR alterations may inform non‑radiopharmaceutical options.¹¹ The NCCN Guidelines also emphasize the importance of BRCA1/2, ATM and other homologous recombination repair in determining eligibility for PARP inhibitor therapy. Incorporating genomic testing into clinical pathways ensures that patients who stand to benefit from targeted therapies are appropriately identified and treated. ²²
• Prior therapies, resistance patterns and urgency of control (e.g., threatened organ function) inform systemic vs. radiopharmaceutical choice.^1,2

Table 2: Multilevel considerations for therapy selection

Drug factors

Efficacy evidence for the indication (overall survival, radiographic progression‑free survival) and toxicity profile (hematologic, hepatic, renal, metabolic, neurologic) should be weighed alongside route, schedule and complexity.^9,10,12

Interactions/contraindications, boxed warnings and radiation safety requirements must be addressed before initiation.^15,11,13

System and access factors

Availability and logistics — radiopharmacy/generator access, dosimetry capacity, isolation and waste handling — often determine tracer and therapy choices in community practice.^3-8 Cost, coverage, prior authorization and supply chain reliability (including tracer half‑life and distribution networks) affect timely care.^7-8 Concordance with society guidelines and shared decision‑making should be documented.^1-2

NCCN Guidelines

Recent updates in radionuclide therapy have expanded FDA indications for both radium-223 (Xofigo) and lutetium-177 vipivotide tetraxetan (Pluvicto), though the NCCN Guidelines have not yet fully reflected these changes. NCCN guideline (v2.2026) updates now indicate Pluvicto for patients with PSMA-positive mCRPC who have been previously treated with both an androgen receptor pathway inhibitor (ARPI) and taxane-based chemotherapy.²²

Xofigo remains recommended for men with symptomatic mCRPC with bone metastases and no visceral disease, typically after prior lines of therapy, despite emerging evidence from the PEACE III trial suggesting benefit in combination with enzalutamide in earlier settings.²⁴

Pluvicto, originally limited to patients with prior ARPI and taxane chemotherapy, received FDA approval in March 2025 for use after ARPI but before chemotherapy, based on the PSMAfore trial. However, NCCN v1.2025 still lists it only for post-chemotherapy use.^23,25

Emerging Clinical Trials
(Selected, 2023–2025)

• Novartis: α‑therapy pipeline with 225Ac‑PSMA‑617 (phase 1) and 225Ac‑PSMA‑R2 (phase I/II) aimed at extending PSMA‑targeted therapy beyond β‑emitters.^16,17
• Telix: ProstACT Global (phase 3)
  evaluates 177Lu‑TLX591 plus standard of care vs. standard of care in PSMA‑
  positive mCRPC progressing on ARPI.¹⁸
• Lantheus/POINT Biopharma: 177Lu‑PNT2002 (PSMA‑I&T) SPLASH phase 3 reported improved rPFS and supports ongoing regulatory interactions.¹⁹
• Bayer: combinations of radium‑223 with ARPIs presented at The American
  Society of Clinical Oncology 2025 suggest rPFS improvement (peer‑review publication pending).²⁰

Juliet Roldan, MBA, CNMT, RT(CT)ARRT, is Administrative Director of Imaging and Theranostics Services at Oncology Consultants in Houston.

AI Acknowledgment: This article was drafted with assistance from ChatGPT (GPT‑5 Thinking).²¹ All content was verified against FDA labels, professional guidelines and peer‑reviewed sources cited; final fact‑check and edits were completed by the author.

References

1. Fendler WP, Eiber M, Calais J, et al. PSMA PET/CT: joint EANM procedure guideline/SNMMI procedure standard for prostate cancer imaging 2.0. J Nucl Med. 2023;64(3):410-425. doi:10.2967/jnumed.122.264089.
2. Eastham JA, Auffenberg GB, Barocas DA, et al. Clinically localized prostate cancer: AUA/ASTRO/SUO guideline. J Urol. 2022;208(4):558-568. doi:10.1097/JU.0000000000002757.
3. Illuccix (gallium Ga‑68 gozetotide) [prescribing information]. US Food and Drug Administration; 2023. Accessed August 15, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/214032s001lbl.pdf.
4. Locametz (gallium Ga‑68 gozetotide) [prescribing information]. US Food and Drug Administration; 2022. Accessed August 15, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215841s000lbl.pdf.
5. Gozellix (TLX007‑CDx; gallium Ga‑68 gozetotide) [prescribing information]. US Food and Drug Administration; 2025. Accessed August 15, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/219592s000lbl.pdf.
6. Telix Pharmaceuticals. FDA approves new prostate cancer imaging agent Gozellix. Press release. March 21, 2025. Accessed August 15, 2025. https://telixpharma.com/news-views/fda-approves-new-prostate-cancer-imaging-agent-gozellix/.
7. Piflufolastat F 18 (Pylarify) [prescribing information]. US Food and Drug Administration; 2021. Accessed August 15, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214793s000lbl.pdf.
8. Posluma (flotufolastat F 18) [prescribing information]. US Food and Drug Administration; 2023. Accessed August 15, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216023s000lbl.pdf.
9. Jani AB, Surasi DS, Eiber M, et al. Diagnostic performance, and safety of 18F‑rhPSMA‑7.3 in men with suspected prostate cancer recurrence (SPOTLIGHT). J Urol. 2023;210(2):299-311. doi:10.1097/JU.0000000000003493.
10. Surasi DS, Maurer T, Preston MA, et al. Diagnostic performance of 18F‑rhPSMA‑7.3 (LIGHTHOUSE). Eur Urol. 2023;84(4):361‑370. doi:10.1016/j.eururo.2023.06.018.
11. US Food and Drug Administration. FDA expands Pluvicto’s mCRPC indication. March 28, 2025. Accessed August 15, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-pluvictos-metastatic-castration-resistant-prostate-cancer-indication.
12. Herrmann K, Rahbar K, Eiber M, et al. 177Lu‑PSMA‑617 (Pluvicto): the first FDA‑approved PSMA‑targeted radioligand therapy. Pharmaceuticals (Basel). 2022;15(10):1292‑1302. doi:10.3390/ph15101292.
13. Xofigo (radium Ra‑223 dichloride) [prescribing information]. US Food and Drug Administration; 2019. Accessed August 15, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/203971s016lbl.pdf.
14. Long‑term data support radium‑223 safety in mCRPC (REASSURE). Urology Times. June 2, 2025. Accessed August 15, 2025. https://www.urologytimes.com/view/long-term-data-support-radium-223-safety-in-mcrpc.
15. Nubeqa (darolutamide) [prescribing information]. US Food and Drug Administration; 2025. Accessed August 15, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/212099s008lbl.pdf.
16. ClinicalTrials.gov. NCT04597411 — 225Ac‑PSMA‑617 dose‑escalation. Accessed August 15, 2025. https://clinicaltrials.gov/study/NCT04597411.
17. Novartis. ClinicalTrials.gov: NCT05983198 — [225Ac] Ac‑PSMA‑R2. Accessed August 15, 2025. https://www.novartis.com/clinicaltrials/study/nct05983198.
18. ClinicalTrials.gov: NCT06520345 — 177Lu‑TLX591 plus SoC vs SoC. Accessed August 15, 2025. https://clinicaltrials.gov/study/NCT06520345.
19. Lantheus & POINT Biopharma. Positive Topline Results: SPLASH Phase 3 (177Lu‑PNT2002). December 18, 2023. Accessed August 15, 2025. https://lantheusholdings.gcs-web.com/news-releases/news-release-details/lantheus-and-point-biopharma-announce-positive-topline-results.
20. Bayer. XOFIGO combination data at ASCO 2025. May 28, 2025. Accessed August 15, 2025. https://www.bayer.com/en/us/news-stories/xofigo-combination-data.
21. OpenAI. ChatGPT (GPT‑5). OpenAI; 2025. Accessed August 18, 2025. https://chat.openai.com.
22. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: prostate cancer. Version 2.2025. Accessed August 18, 2025. https://www.nccn.org.
23. National Comprehensive Cancer Network. Prostate Cancer. Version 1.2025. NCCN Clinical Practice Guidelines in Oncology. Published December 4, 2024. Accessed August 18, 2025. https://www.nccn.org.
24. Bayer. Xofigo Combination Data from PEACE III Trial. Published 2024. Accessed August 18, 2025. https://www.bayer.com.
25. Novartis. FDA Approves Novartis Radioligand Therapy Pluvicto® for Earlier Use in PSMA-Positive mCRPC. Published March 2025. Accessed August 18, 2025. https://www.novartis.com.