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PEER-TO-PEER CLINICAL CONVERSATIONS
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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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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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Monitoring the Marrow: Hematologic Toxicity in the Treatment of Advanced Prostate Cancer
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Daniel Childs, MD, FACP
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| Daniel Childs examines hematologic toxicity following lutetium therapy. He presents institutional data from Mayo Clinic showing 14 cases of MDS and 12 of CCUS among 405 treated patients with a latency of under one year, alongside Peter Mac data reporting therapy-related myeloid neoplasms in 1% of 381 patients.
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| Monitoring in mCRPC
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| Gunhild von Amsberg, MD
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| Gunhild von Amsberg emphasized that monitoring in mCRPC should move beyond PSA alone, since modern imaging and biomarkers can reveal progression that conventional approaches miss. She highlighted PSMA PET/CT, whole-body MRI, CTCs, and serum markers as important tools for more biologically informed follow-up, while noting that prospective trials still need to prove these approaches improve outcomes.
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| Long-Term Marrow Toxicity: Rates and Risk Factors
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| Daniel Childs, MD
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| Daniel Childs highlighted that 177Lu-PSMA-617 can cause persistent cytopenias and therapy-related myeloid neoplasms, with real-world rates around 1–5% and latency as short as months to a few years. He noted clonal hematopoiesis, especially in DDR genes like PPM1D and TP53, likely modifies risk and proposed a radiogenomic framework to guide monitoring and mitigate toxicity.
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| Lesion Absorbed Dose-Response Relationship in Patients with Metastatic Castration-Resistant Prostate Cancer Undergoing [177Lu]Lu-PSMA-617 Radiopharmaceutical Therapy - Beyond the Abstract
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| Milan Grkovski, Simone Krebs, Joseph O'Donoghue et al.
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| This study found a moderate but meaningful relationship between higher lesion-absorbed dose and better response to 177Lu-PSMA-617, with patients receiving >7.5 Gy volume-weighted mean dose having significantly deeper PSA declines, longer biochemical progression-free survival, and longer overall survival.
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Plasma Extracellular Vesicle Proteomics Nominates Candidate Biomarkers of 177Lu-PSMA-617 Outcomes in Metastatic Prostate Cancer Patients - Beyond the Abstract
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| Ali Arafa, MD, Justin Hwang, PhD, Justin Drake, PhD, and Emmanuel Antonarakis, MD
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| This prospective study of 100 mCRPC patients found that plasma extracellular vesicle proteomics can identify biomarkers linked to 177Lu-PSMA-617 outcomes, with high EV levels of PSMA, B7-H3, Trop-2, and STEAP1 associated with worse survival and proteins like CXCR4 and CD46 linked to better outcomes. The researchers also used ALAN to reveal coordinated protein networks and highlighted ABCB1 as a potential marker to help distinguish patients who may benefit more from radioligand therapy versus chemotherapy.
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