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PEER-TO-PEER CLINICAL CONVERSATIONS |
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Adaptive Dosing of Lutetium PSMA Based on Imaging and PSA Response
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Louise Emmett, MD, MBChB, FRACP, FAANMS
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| Louise Emmett discusses lutetium-177 PSMA therapy optimization. In the ENZA-p trial, 68% of patients showed PSMA upregulation within 15 days of starting enzalutamide; those with upregulation had a six-month progression-free survival on enzalutamide alone, compared to 13 months in those without upregulation.
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Combination Approaches in Lutetium PSMA Therapy in mCRPC
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Michael Hofman, MBBS, FRACP, FAANMS, FICIS, GAICD
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| Michael Hofman reviews limitations of lutetium-177 PSMA-617 and combination strategies. In the TheraP trial comparing lutetium to cabazitaxel, PSA-50 response rates were 66% versus 37% and objective CT response rates were 49% versus 24%, yet overall survival was similar, which Dr. Hofman attributes to lutetium's lesser effect on preventing new metastasis formation.
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Clinical Scenario and Patient Preference Guide Radium-223 Use in mCRPC
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Daniel Heinrich, MD
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| Daniel Heinrich discusses patient selection for radium-223. No validated molecular, radiologic, or nuclear medicine biomarkers currently exist for selecting patients, leaving clinical scenario and patient preference as the primary guides.
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Three Priority Targets Beyond PSMA for Prostate Cancer Radioligand Therapy
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Ken Herrmann, MD, MBA
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| Ken Herrmann discusses emerging radioligand therapy targets beyond PSMA. Dr. Herrmann names ACP3, B7-H3, and STEAP1/STEAP2 as his top three targets, noting that ACP3 may have higher affinity than PSMA, shows complementary or sometimes exclusive uptake in PSMA-negative patients, and has tumor retention measured in days rather than hours.
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The 2026 Advanced Prostate Cancer Consensus Conference
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| How to Optimally Select Patients for Lutetium-PSMA Radioligand Therapy?
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| Michael Morris, MD
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| Michael Morris said that Lutetium-PSMA therapy is clearly beneficial after both an androgen receptor pathway inhibitor and chemotherapy, and it is also a strong option earlier because it improves radiographic progression-free survival and quality of life. The best candidates tend to have high PSMA avidity and low ctDNA fraction, while patients with HRR mutations—especially BRCA—should generally receive genomically directed therapy first.
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| How to Make Best Use of Lutetium-PSMA Radioligand Therapy?
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| Louise Emmett, MD, MBChB, FRACP, FAANMS
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| Louise Emmett’s APCCC 2026 message was that Lutetium-PSMA is moving earlier: it already has a clear role in post-ARPI/post-chemotherapy mCRPC, but PSMAddition suggests it may also help in mHSPC. She highlighted that the best use may come from combining it with AR pathway inhibition, using adaptive or intensified dosing strategies, and selecting patients with biomarkers such as high PSMA avidity and low ctDNA fraction.
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| How to Optimally Select Patients for Radionuclide Therapy with Radium-223?
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| Daniel Heinrich, MD
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| Daniel Heinrich’s APCCC 2026 message was that radium-223 is best used as part of a broader life-prolonging treatment sequence in mCRPC, not as a biomarker-driven precision therapy, because there are currently no validated biomarkers to select patients for it. He emphasized using it mainly for bone-predominant disease without major visceral metastases, combining it with bone-protecting agents, and considering it especially in first-line mCRPC with enzalutamide or as re-treatment in selected patients.
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| Beyond PSMA: New Theranostic Targets Approaching near Term Clinical Implementation
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| Ken Herrmann, MD
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| Ken Herrmann’s APCCC 2026 message was that there are many promising targets beyond PSMA, but none are ready for near-term routine use yet. His leading candidates were ACP3, STEAP1/2, and B7-H3, which already have encouraging first-in-human or early translational data and could become the next wave of prostate cancer theranostics.
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| Beyond Monotherapy: PSMA Combination Strategies Are Arriving
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| Michael Hofman, MBBS
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| Michael Hofman’s APCCC 2026 talk argued that PSMA combinations are arriving, with the clearest signal so far from adding 177Lu-PSMA-617 to enzalutamide or other systemic backbones to deepen responses and improve progression-free survival. He highlighted that monotherapy works well in PSMA-positive mCRPC, but combination approaches may better address resistant clones and are now moving into phase 3 testing across hormone therapy, chemotherapy, immunotherapy, PARP inhibition, and radiotherapy.
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