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PEER-TO-PEER CLINICAL CONVERSATIONS
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MEVPRO-3 Trial: Enzalutamide With or Without Mevrometostat in Metastatic Hormone-Sensitive Prostate Cancer
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Neeraj Agarwal, MD, FASCO
Neeraj Agarwal describes the MEVPRO-3 trial design. The trial enrolls 1,000 patients with newly diagnosed metastatic hormone-sensitive prostate cancer randomized to ADT plus enzalutamide versus ADT plus enzalutamide plus mevrometostat, an EZH2 inhibitor.
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Practical Approaches to Genetic Testing in Metastatic Hormone-Sensitive Prostate Cancer
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Emmanuel Antonarakis, MD
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| Emmanuel Antonarakis recommends germline and somatic testing for all metastatic prostate cancer patients. Dr. Antonarakis orders germline testing pre-emptively, reserving genetic counseling for pathogenic variants when first-degree relatives face 50% inheritance risk.
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Large-Scale Data Linkage Reveals Genomic Differences in De Novo Metastatic Prostate Cancer
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Shalini Moningi, MD
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| Shalini Moningi speaks with Angela Jia about a real-world analysis evaluating the Decipher® Prostate Genomic Classifier in patients with de novo metastatic prostate cancer. The study found that patients presenting with metastatic disease had higher Decipher scores, higher rates of PTEN inactivity, and more luminal B subtype tumors compared with matched patients with localized disease, supporting further study of genomic classifiers for risk stratification and future treatment intensification or de-intensification strategies.
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| Mevrometostat in Advanced Prostate Cancer: Targeting EZH2 Across the Disease Continuum Through the MEVPRO Clinical Trial Program
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| Zachary Klaassen, MD, MSc
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| Mevrometostat is an EZH2 inhibitor being tested across advanced prostate cancer in the MEVPRO program, with studies in post-abiraterone mCRPC, ARPI-naïve mCRPC, and ARPI-naïve mCSPC. The goal is to see whether targeting epigenetic resistance can prolong the benefit of enzalutamide and delay progression across the disease continuum.
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| Precision Oncology: How to Apply New Biomarkers in Clinical Practice
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| Joshua Lang, MD, MS
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| Joshua Lang emphasized that the new biomarkers discussed are still mostly prognostic, not fully predictive, so prospective validation is needed before they can routinely guide treatment selection. He highlighted Decipher for risk stratification in prostate cancer, AI-derived pathology for potential docetaxel benefit prediction, and miR-371 as a promising circulating biomarker in testicular cancer, but cautioned that clinical utility remains unproven for many real-world decisions.
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| The Diversity and Clinical Relevance of Germline DNA Damage Repair Gene Variants in 3005 Patients with Metastatic Prostate Cancer
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| Sofie Tolmeijer, PhD
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| A large ASCO GU 2026 analysis found germline DDR variants in about 9% of 3,005 men with metastatic prostate cancer, with BRCA2 the most common and most clinically aggressive. BRCA2 carriers had more high-grade disease, faster progression to castration resistance, and markedly shorter overall survival, supporting broader germline testing that includes structural variants.
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| Opening the Black Box: Biologic Pathways Underlying Multimodal Digital-Pathology Artificial Intelligence in Metastatic Prostate Cancer
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| Amol Shetty, PhD, MS
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| Amol Shetty’s ASCO GU 2026 poster showed that multimodal digital-pathology AI is capturing real prostate cancer biology, not just producing a black-box score. The model’s high-attention regions were linked to aggressive pathways like MYC signaling, EMT, DNA repair, and stromal fibroblast activity, with spatial transcriptomics confirming that the AI was highlighting biologically active tumor compartments.
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