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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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Selecting Therapy in Metastatic Hormone-Sensitive Prostate Cancer: A Multi-Step Approach
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Pedro Barata, MD, MSc, FACP
Pedro Barata discusses therapy selection and patient goals in metastatic hormone-sensitive prostate cancer. Dr. Barata describes framing treatment decisions around tumor volume using CHAARTED criteria, timing of metastatic disease, and performance status, with ADT plus an ARPI as the standard backbone.
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Doublet Versus Triplet Intensification in Metastatic Hormone-Sensitive Prostate Cancer
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Jacqueline Brown, MD
Jacqueline Brown discusses doublet versus triplet therapy in metastatic hormone-sensitive prostate cancer with Neeraj Agarwal, drawing on her AUA 2026 presentation.
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| Genomic and Transcriptomic Correlates of Deep PSA Response in Patients with mHSPC
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| Emmanuel Antonarakis, MD
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| In 525 men with mHSPC, a deep PSA response at 6 months (<0.1<0.1<0.1 ng/mL) was strongly associated with better survival, including 83% 36-month overall survival versus 66% in men with higher PSA and an adjusted HR of 0.51. SPOP alterations were more common in deep responders, while ZFHX3 alterations were enriched in poorer responders, but no major transcriptomic differences were seen for targets like PSMA, TROP2, B7-H3, or STEAP1.
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| How to Test for Relevant Molecular Alterations in mHSPC?
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| Joaquin Mateo, MD, PhD
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| Joaquin Mateo presented a practical framework for molecular testing in mHSPC, emphasizing that all patients being considered for treatment intensification should undergo at least HRR gene testing, with germline testing also considered for all patients. He also suggested that, when feasible, broader testing such as MMR and other prognostic biomarkers could be incorporated, ideally as part of a comprehensive diagnostic workup at baseline, with additional testing later if the disease evolves.
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| Real-World Characteristics, HRR Mutation Testing, Treatment Patterns, and Outcomes of Patients with mCSPC in the US Community Oncology Setting
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| Manojkumar Bupathi, MD, MS
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| In this real-world community oncology cohort of 300 men with mCSPC, HRR-mutated patients had numerically shorter overall survival and real-world progression-free survival than those without HRR mutations, with the difference most apparent in de novo metastatic disease. Nearly half of HRR-positive patients had BRCA alterations, reinforcing the value of early HRR testing to help identify higher-risk patients who may benefit from earlier targeted treatment strategies.
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| An AI-Based Pathology Classifier to Predict Benefit from Enzalutamide in mHSPC from ENZAMET (ANZUP 1304)
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| Sebastian Medina, MSc
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| In the ENZAMET analysis, the AI-based APIC biomarker identified patients who benefitted from adding enzalutamide to ADT: APIC-negative men had an overall survival advantage, while APIC-positive men did not. APIC-positive disease also looked more immune-cold and may represent a group that could benefit more from docetaxel-based intensification.
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| Predictors of Treatment Duration in Patients with mHSPC Treated with ENZA: a Post Hoc Analysis of ARCHES
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| Andrew Armstrong, MD, MSc
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| In ARCHES, longer enzalutamide treatment duration was associated with better baseline and disease characteristics, deeper PSA responses, and fewer treatment-limiting adverse events. Progressive disease remained the most common reason for stopping therapy, but adverse events and treatment withdrawal were much more frequent in patients with short treatment duration, suggesting better toxicity and comorbidity management may improve persistence.
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| Real-World Genetic Testing Patterns in Prostate Cancer Assessed via AI: Implications for NCCN Guideline Implementation
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| Mitchell Singstock, MD
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| In a large community oncology practice, NCCN-indicated germline and somatic testing for prostate cancer was frequently underused, although testing rates improved from 2023 to 2025. An AI-based approach to applying NCCN criteria showed high agreement with manual review and could help scale identification of patients who should receive genetic testing.
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