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PEER-TO-PEER CLINICAL CONVERSATIONS
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Treatment Intensification in Older and Comorbid Patients with Metastatic Hormone-Sensitive Prostate Cancer
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Alicia Morgans, MD, MPH
Alicia Morgans discusses treatment intensification in older and comorbid patients with metastatic hormone-sensitive prostate cancer. Dr. Morgans draws on clinical tools including the mini-COG and the G8, an eight-question frailty screen where a score below 14 is associated with increased non-cancer mortality.
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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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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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| PSA Outcomes of Darolutamide and ADT in Patient Subgroups by Age, Comorbidities, and Concomitant Medications: ARANOTE Post Hoc Analysis
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| Fred Saad, MD, FRCS, CQ, FCAHS
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| Darolutamide plus ADT improved PSA outcomes in mHSPC across all age, comorbidity, and concomitant medication subgroups in ARANOTE, with consistently higher PSA <0.2 ng/mL rates than placebo plus ADT. The benefit also held in patients with cardiovascular or metabolic disorders, providing clinically relevant data for treatment selection in older patients and those with substantial comorbidity.
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| EORTC GUCG 2238 – DE-ESCALATE: A Pragmatic Trial to Revisit Intermittent ADT in mHSPC in the Era of New ARPIs
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| Fabio Turco, MD
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| DE-ESCALATE is a pragmatic phase III trial testing whether intermittent maximum androgen blockade (ADT + ARPI, with docetaxel/radiation allowed) is safe in mHSPC patients who achieve PSA ≤0.2 ng/mL within 6–12 months, compared with continuing treatment. Its co-primary endpoints are feasibility and overall survival non-inferiority at 3 years, with secondary aims on toxicity, quality of life, and resource use.
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| Major Adverse Cardiovascular Events in ARPI-Treated Patients with mCSPC
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| Linden Huhmann
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| In a real-world VA cohort of 11,788 men with mCSPC, darolutamide was associated with lower 1-year major adverse cardiovascular event incidence than abiraterone, with a significant 22% hazard reduction in doublet therapy and a similar trend in triplet therapy. These findings suggest these findings may help inform ARPI selection in patients with elevated cardiovascular risk.
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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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| Emmanuel Antonarakis discusses a study in which 525 mHSPC patients, achieving PSA <0.1 ng/mL at 6 months was strongly linked to better survival, with 36-month OS of 83% vs 66% and HR 0.51 for overall survival. SPOP alterations were enriched in deep responders, ZFHX3 alterations in poorer responders, but no transcriptomic differences were seen for targets like PSMA, TROP2, B7-H3, or STEAP1.
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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 US community oncology cohort of 300 mCSPC patients, those with HRR mutations had numerically shorter overall survival and progression-free survival than non-carriers, with the worst outcomes in de novo metastatic disease. Nearly half of HRRm carriers had BRCA mutations, supporting early HRRm testing and potentially earlier use of targeted therapies for this higher-risk group.
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| Which Patients Should Receive "DOUBLE" Systemic Therapy in mHSPC
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| Robert Jones, MD, PhD
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| Robert Jones recommended doublet therapy for mHSPC patients with low-risk features: BRCA wild type, PTEN competent, PSMA negative, and low-volume metachronous disease. Biomarkers like high Decipher GC score and poor 6-month PSA response help identify patients who may benefit from triplet escalation, while early deep PSA response suggests good outcomes and possible overtreatment.
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