Key Topics

Molecular Imaging & Therapy Basics

Dr. Ulaner begins with an overview of molecular imaging and therapy: cancer cells express targets such as PSMA (Prostate Specific Membrane Antigen), which can be bound by specially designed agents. When linked to imaging isotopes, these agents allow highly sensitive PET scans to detect prostate cancer. When linked to therapeutic isotopes, they deliver radiation directly to cancer cells, shrinking disease while sparing most normal tissue.

Pluvicto and Clinical Impact

The landmark NEJM trial established that Lutetium-177 PSMA-617 (Pluvicto) improves survival compared to standard care in metastatic castration-resistant prostate cancer. While not a cure, it significantly reduces tumor burden and extends life, with median benefit of about 4–6 months on average, and in some cases years of added survival. Dr. Ulaner emphasized that individual responses vary widely.

Current and New Clinical Trials

Two key clinical trials at Hoag are highlighted:

 • Actinium-225 PSMA trial: For patients who have already received Pluvicto and progressed. Actinium delivers alpha radiation (100x stronger than beta), often with fewer systemic side effects, though salivary gland toxicity (dry mouth) is more pronounced. This option may be preferable to chemotherapy for many patients.

 • Pluvicto ± ARPI trial (newly opened): For patients who have had one prior ARPI (abiraterone, enzalutamide, darolutamide, or apalutamide) and then progressed. Patients may receive Pluvicto alone or Pluvicto plus another ARPI. Importantly, Novartis provides the medication free of charge for participants.

Practical Questions Answered

The Q&A addressed:

 • When to order PSMA PET: After prostatectomy, a PSA ≥0.2 ng/mL usually qualifies. Post-radiation, thresholds depend on PSA rise above nadir.

 • Effect on treatment decisions: PSMA PET alters management in over 50% of biochemical recurrence cases, ~⅓ of high-risk newly diagnosed cases, and 10–15% of patients being evaluated for therapy.

 • Side effects: Pluvicto is generally well tolerated compared to chemotherapy. Actinium therapy has more dry-mouth issues but often less bone marrow toxicity.

 • Access to trials: Patients from outside California can enroll if they can travel to Hoag or to other sites nationwide as they open.

 • Hip replacements: Do not interfere with PSMA therapy or imaging.

 • Quality of life: Radioligand therapies usually provide “good months of life,” with relatively mild side effects compared to chemotherapy.

Key Takeaways

 • Pluvicto is a proven life-extending therapy for advanced prostate cancer.

 • Actinium-225 PSMA offers a promising next step for patients progressing after Pluvicto.

 • New trials combining Pluvicto with ARPIs may improve outcomes, with drugs supplied at no cost.

 • PSMA PET imaging is transforming management, guiding both diagnosis and therapy selection.