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PEER-TO-PEER CLINICAL CONVERSATIONS
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Radiopharmaceuticals in Prostate Cancer: Patient Selection and Treatment Sequencing
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Dustin Boothe, MD, Neal Shore, MD, FACS, and Tanya Dorff, MD
Tanya Dorff, Neal Shore, and Dustin Boothe discuss patient selection and treatment sequencing for lutetium-177 PSMA across the pre- and post-chemotherapy mCRPC settings. The panel relies on PSMA PET avidity and the broader clinical picture to guide sequencing decisions, while emphasizing that NGS remains essential for identifying DNA repair alterations such as BRCA2 that may favor PARP inhibitors.
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PSMAddition Trial of ADT, ARPI, and Lutetium-177 in Metastatic Hormone-Sensitive Prostate Cancer
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Fred Saad, CQ, MD, FRCS, FCAHS
Fred Saad presents a PSMAddition subgroup analysis examining rPFS benefit by disease volume and timing in the trial of ADT plus any ARPI with or without lutetium-177 in metastatic hormone-sensitive prostate cancer.
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The LuRa Study of Radium-223 After Prior Lutetium-177-PSMA-617 in mCRPC
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Kambiz Rahbar, MD
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| Kambiz Rahbar presents the LuRa study, a retrospective four-center German analysis of 67 heavily pretreated mCRPC patients who received radium-223 after prior lutetium-177 PSMA therapy.
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| CONVERGE-01 Part 3: Ac-225 Rosopatamab Tetraxetan (CONV01-α) in 177Lu-PSMA-617 Pretreated mCRPC
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| Michael Morris, MD
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| In CONVERGE-01 Part 3, the alpha-emitting PSMA-targeted antibody conjugate Ac-225 rosopatamab tetraxetan (CONV01-α) was evaluated in 35 men with mCRPC previously treated with 177Lu-PSMA. The analysis reported safety and preliminary efficacy findings, including a 40% PSA50 response rate and a median radiographic PFS of 8.4 months in the target dose group, with no reported nephrotoxicity or high-grade xerostomia.
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| How to Better Personalize Treatment with 177Lu-PSMA-617
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| Louise Emmett, MD, MBChB, FRACP, FAANMS
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| Personalizing 177Lu-PSMA-617 therapy involves refining patient selection beyond binary PSMA PET eligibility by integrating quantitative imaging (e.g., SUVmean, total tumor volume), circulating tumor DNA fraction, and early on-treatment biomarkers (PSA decline plus PSMA-TTV changes) to identify non-responders and adapt dosing.
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| Predicting Early PSA Response to 177Lu-PSMA Therapy using Baseline PET Imaging Biomarkers and Cycle 1 Dosimetry
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| Molly Roseland, MD
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| Molly Roseland discusses a retrospective study of 28 men receiving 177Lu-PSMA, in which higher baseline whole-body tumor SUVmean on PSMA PET and higher cycle‑1 tumor absorbed dose were both associated with greater early PSA declines and better responses after cycle 2 and at 3 months post‑therapy, with mean absorbed dose ~12.3 Gy in responders vs 4.5 Gy in non-responders and SUVmean ~11.1 vs 6.0.
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| Phase 2 Expansion Study of 212Pb-ADVC001 in Metastatic Prostate Cancer: The TheraPb Trial
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| Aaron Hansen, MD
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| TheraPb is a phase 2 expansion study of the alpha-emitting PSMA radioligand 212Pb-ADVC001 in metastatic prostate cancer, testing two dose levels with adaptive dosing across mHSPC, Lu-PSMA–naïve mCRPC, and post-Lu-PSMA mCRPC. The trial is designed to assess PSA, imaging, safety, dosimetry, and biomarkers over up to 5 years, building on phase 1b data that showed promising activity and no dose-limiting toxicities.
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Emerging Evidence for Sequencing and Combining PSMA-Based Therapies in Prostate Cancer - Beyond the Abstract
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| Sola Adeleke, PhD, MBBS
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| This review argues that PSMA-targeted treatment is moving from single-agent use to a more strategic framework built around sequencing, combinations, and biomarker-guided selection. It highlights emerging evidence that earlier use of PSMA radioligand therapy, or pairing it with AR-targeted therapy, PARP inhibition, immunotherapy, chemotherapy, or other PSMA-directed platforms, may deepen and prolong responses, although prospective survival data and standardized biomarkers are still needed before these strategies can be broadly adopted.
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| Metabolic Tumor Phenotype Determines Radiation Delivery and Outcomes in PSMA Radiopharmaceutical Therapy for Advanced Prostate Cancer
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| Wen Sijie, PhD
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| In a retrospective study of 35 mCRPC patients treated with 177Lu-PSMA, lesions that were PSMA-positive/FDG-positive (concordant, metabolically aggressive) received lower absorbed doses than PSMA+/FDG− lesions, and only the mean dose to these PSMA+/FDG+ lesions stratified PSA response and progression-free survival.
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