3 Things You Should Know About PSMA-Directed Imaging and Radioligand Therapy in Prostate Cancer

LEARNING OBJECTIVES

Upon successful completion of this activity, you should be better prepared to:

• Evaluate the diagnostic and prognostic value of prostate-specific membrane antigen (PSMA) PET imaging and integrate imaging results into treatment planning for patients with advanced prostate cancer

• Develop evidence-based sequencing strategies incorporating PSMA radioligands alongside androgen receptor pathway inhibitors, chemotherapy, and novel investigational agents

• Identify real-world logistical, operational, and access-related barriers to PSMA-targeted imaging and therapy, and propose collaborative, multidisciplinary solutions to overcome them

RELEASE DATE: February 1, 2026

EXPIRATION DATE: February 1, 2027

Accreditation/Credit Designation

Physicians’ Education Resource^®, LLC, is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Physicians’ Education Resource^®, LLC, designates this enduring material for a maximum of 0.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Acknowledgement of Commercial Support

This activity is supported by an educational grant from Novartis Pharmaceuticals Corporation.

Off-Label Disclosure and Disclaimer

This activity may or may not discuss investigational, unapproved, or off-label use of drugs. Learners are advised to consult prescribing information for any products discussed. The information provided in this activity is for accredited continuing education purposes only and is not meant to substitute for the independent clinical judgment of a health care professional relative to diagnostic, treatment, or management options for a specific patient’s medical condition. The opinions expressed in the content are solely those of the individual faculty members, and do not reflect those of PER^® or any company that provided commercial support for this activity.

INSTRUCTIONS FOR PARTICIPATION AND HOW TO RECEIVE CREDIT

1. Read this activity in its entirety.

2. Go to https://www.gotoper.com/cfs25psma-postref to access and complete the posttest.

3. Answer the evaluation questions.

4. Request credit using the drop-down menu.

YOU MAY IMMEDIATELY DOWNLOAD YOUR CERTIFICATE.

Prostate specific membrane antigen (PSMA)-directed imaging and radioligand therapy have transformed prostate cancer care across disease stages. PSMA PET/CT improves diagnostic precision and frequently alters management, while PSMA-directed radionuclide therapies have demonstrated meaningful clinical benefit for appropriately selected patients with advanced disease. As ongoing trials explore earlier disease settings, combination strategies, and next-generation radioligands, continued education will be essential to keep pace with the rapidly evolving PSMA-directed therapeutic landscape. Here are 3 things you should know about PSMA-directed imaging and radioligand therapy in prostate cancer.

1) PSMA is a cornerstone of modern prostate cancer care, but its clinical utility depends on heterogeneity and context

PSMA is a type II transmembrane glycoprotein that is markedly overexpressed in advanced prostate cancer, particularly as tumors transition to castration resistance. Its biologic characteristics have enabled PSMA to function as both a high-sensitivity diagnostic biomarker and a therapeutic target, forming the foundation of modern theranostic strategies.^1,2 From a diagnostic perspective, PSMA-targeted PET/CT imaging has demonstrated superior sensitivity and specificity compared with conventional imaging modalities. PSMA PET consistently outperforms bone scans and CT for initial staging and for detecting biochemical recurrence, enabling earlier identification of metastatic disease and more precise treatment planning.^3-5

PSMA-targeted radionuclide therapy uses a PSMA-binding ligand linked to a β-emitting radionuclide such as lutetium-177 to bind PSMA-expressing tumor cells, undergo receptor-mediated internalization, and deliver focused radiation to malignant tissue. This targeted mechanism allows preferential cytotoxicity while limiting exposure to most surrounding normal tissues.^6,7 However, PSMA is not uniformly expressed across all tumors or disease sites. Inter- and intrapatient heterogeneity of PSMA expression has direct implications for both imaging interpretation and therapeutic efficacy.^8,9 A subset of patients demonstrate PSMA-low or PSMA-negative disease, which may limit benefit from PSMA-directed strategies.

Why PSMA Matters

PSMA should be viewed as a powerful, yet imperfect biomarker. Optimal use requires understanding disease biology, correlating imaging findings with clinical context, and recognizing scenarios in which additional imaging or biopsy may be warranted.

2) PSMA PET has redefined diagnostic precision and frequently modifies management

PSMA PET/CT has fundamentally shifted the diagnostic paradigm in prostate cancer by offering substantially greater sensitivity and accuracy than conventional imaging modalities, including CT, MRI, and bone scans. It is particularly valuable for frontline staging of unfavorable intermediate-, high-, and very high–risk disease.^3,10

In the randomized proPSMA trial, PSMA PET/CT demonstrated approximately 27% higher diagnostic accuracy than conventional imaging (92% vs 65%) and significantly improved detection of pelvic nodal and distant metastatic disease.³ Similar advantages have been demonstrated across multiple prospective and real-world studies.^11,12

The benefits of PSMA PET are especially pronounced in biochemical recurrence. Compared with earlier tracers such as choline and fluciclovine, PSMA PET detects disease at lower prostate-specific antigen (PSA) levels and with greater anatomic precision, often resulting in clinically meaningful stage migration.^4,5,13,14

Importantly, PSMA PET frequently changes management decisions rather than simply confirming known disease. Thus, in routine practice, PSMA PET should be considered for: (1) initial staging of intermediate- to high-risk disease, (2) localization of recurrence at low PSA levels, and (3) confirming eligibility for PSMA-directed radioligand therapy. Clinicians must also remain mindful of limitations. False-positive uptake can occur in benign structures such as sympathetic ganglia, healing fractures, hemangiomas, or Paget disease.¹⁵ Accurate interpretation relies on reader expertise and standardized reporting frameworks such as PSMA-RADS (reporting and data system) and PROMISE (prostate cancer molecular imaging standardized evaluation).¹⁶

PSMA PET as a decision-changing tool

Early integration of PSMA PET can redefine staging, uncover occult disease, and directly alter management strategies. Taken together, advances in PSMA biology, high-precision molecular imaging, and targeted radioligand therapy have established an integrated theranostic approach to prostate cancer care. PSMA functions as a unifying biomarker that links diagnostic staging, disease characterization, and treatment selection across the disease continuum from initial risk stratification to advanced metastatic settings. Understanding how these components intersect and the team required to implement effective care is essential for translating PSMA-directed strategies into meaningful, real-world clinical decisions (Figure 1).^17-19

3) PSMA-targeted radioligand therapy is highly effective, but success depends on patient selection, multidisciplinary care, and operational readiness

Lutetium Lu 177 vipivotide tetraxetan (¹⁷⁷Lu–PSMA-617) is an FDA-approved PSMA-targeted radioligand therapy for patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) following androgen receptor pathway inhibitor (ARPI) therapy, including patients who are appropriate to delay taxane‑based chemotherapy and those who have previously received taxane‑based chemotherapy.²⁰

In the phase 3 VISION trial (NCT03511664), the addition of ¹⁷⁷Lu-PSMA-617 to standard of care significantly improved overall survival (15.3 vs 11.3 months) and radiographic progression-free survival compared with standard care alone.⁷ The PSMAfore trial (NCT04689828) further demonstrated improved radiographic progression-free survival in taxane-naive patients who had progressed on one prior ARPI. No difference in overall survival was found, but results were confounded by significant crossover from the control arm.²¹ These data support the use of radioligand therapy earlier in the mCRPC disease course.

Appropriate patient selection extends well beyond confirmation of PSMA positivity on PET imaging. Disease burden, metastatic pattern, prior therapies, performance status, and laboratory markers all influence outcomes. High baseline PSMA uptake has been associated with improved response and survival, whereas liver metastases, particularly when PSMA-negative, consistently predict poorer prognosis.^7,14,17

There are a number of PSMA-directed radionuclide therapies in development. Treatment requires proactive patient counseling regarding expected toxicities, including xerostomia, dry eyes, fatigue, nausea, and cytopenias, which reflect off-target uptake in normal tissues.^{1,2,7,14,19-21}

Real-world implementation introduces additional complexity. Successful delivery requires close coordination among medical oncology, nuclear medicine, pharmacy, nursing, and radiation safety teams (Figure 1). Establishing a radioligand therapy program involves regulatory compliance, infrastructure investment, and workflow redesign.^17-19 Short radiopharmaceutical shelf life and advance ordering requirements further complicate scheduling and access.¹⁸

Delivering radioligand therapy successfully in practice

Maximizing benefit from PSMA-directed radionuclide therapies requires careful patient selection, multidisciplinary coordination, and operational preparedness.

Key References

3. Hofman MS, Lawrentschuk N, Francis RJ, et al. Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study. Lancet. 2020;395(10231):1208-1216. doi:10.1016/s0140-6736(20)30314-7

7. Sartor O, de Bono J, Chi KN, et al. Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021;385(12):1091-1103. doi:10.1056/NEJMoa2107322

13. Fendler WP, Eiber M, Beheshti M, et al. PSMA PET/CT: joint EANM procedure guideline/SNMMI procedure standard for prostate cancer imaging 2.0. Eur J Nucl Med Mol Imaging. 2023;50(5):1466-1486. doi:10.1007/s00259-022-06089-w

For FULL References List, visit
https://www.gotoper.com/cfs25psma-postref

CME Posttest Questions

1. A man aged 68 years with newly diagnosed high-risk prostate cancer undergoes staging with conventional imaging, which shows no metastases. His physician orders a prostate-specific membrane antigen (PSMA) PET/CT for further assessment. Which of the following best describes a clinical advantage of PSMA PET/CT in the evaluation of patients with prostate cancer?

A. It provides higher sensitivity than conventional CT in detecting metastatic disease but requires confirmatory bone scan given its lower specificity.

B. It detects micrometastatic disease with significantly higher accuracy than conventional imaging, often leading to stage migration and changes in management.

C. It has demonstrated superior sensitivity and specificity for identifying local recurrence but has limited value for initial staging.

D. It has demonstrated superior sensitivity and specificity for assessing treatment response but has limited value for initial staging.

2. A man aged 72 years with metastatic castration-resistant prostate cancer previously treated with androgen deprivation therapy and an androgen receptor (AR) pathway inhibitor presents with PSMA-positive lesions on PET/CT and no evidence of PSMA-negative disease. He is chemotherapy eligible but prefers to delay docetaxel. Based on current evidence, which approach is most appropriate?

A. Counsel patient that starting docetaxel now would likely maximize his overall survival.

B. Switch to a different AR pathway inhibitor.

C. Assess microsatellite stability and add immunotherapy if microsatellite instability–high.

D. Initiate PSMA-directed β-emitting radioligand therapy.

3. Which multidisciplinary strategy most effectively addresses real-world barriers to implementing PSMA-targeted imaging and therapy?

A. Establishing dedicated theranostic teams with nuclear medicine, oncology, radiopharmacy, and nursing expertise

B. Expanding oncology-led practices with selective nuclear medicine consultation to increase local treatment capacity

C. Implementing decentralized delivery models led by local imaging centers to expand geographic access

D. Referring all patients to tertiary centers

Claim Your CME Credit at: https://www.gotoper.com/cfs25psma-postref

To learn more about this topic, including information on clinical application, emerging strategies, and real-world barriers, go to https://www.gotoper.com/cfs25psma-activity

CME Provider Contact Information

Physicians’ Education Resource^®, LLC
259 Prospect Plains Road, Building H, Cranbury, NJ 08512
Toll-Free: 888-949-0045
Local: 609-378-3701
Fax: 609-257-0705
info@gotoper.com