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PEER-TO-PEER CLINICAL CONVERSATIONS
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The CAPItello-281 Trial and FDA Approval of Capivasertib in PTEN-Loss mHSPC
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Elisabeth Heath, MD, FACP
Elisabeth Heath discusses the FDA approval of capivasertib for PTEN-deficient metastatic hormone-sensitive prostate cancer, reviewing CAPItello-281 data in de novo patients randomized to capivasertib plus abiraterone versus abiraterone alone, both with ADT.
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Multidisciplinary Strategies for Managing the Complexities of mHSPC Care
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Neal Shore, MD, FACS
Neal Shore discusses metastatic hormone-sensitive prostate cancer management with emphasis on moving beyond ADT monotherapy. Real-world data shows 25-35% of patients still receive ADT monotherapy, which Dr. Shore argues should decrease to under 10%.
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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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| 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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| How to Select Patients with mHSPC for ADT plus an ARPI plus a Targeted Therapy (PARP or AKT Inhibition)?
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| Shahneen Sandhu, MBBS, FRACP
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| Shahneen Sandhu emphasized that selecting mHSPC patients for ADT plus ARPI plus targeted therapy should be biomarker-driven, because intensification adds morbidity and not all patients need the same escalation. Dr. Sandhu highlighted two major pathways: HRR-deficient disease, where PARP inhibitor combinations show benefit especially in BRCA-altered tumors, and PTEN-deficient disease, where AKT inhibition improved radiographic progression-free survival and may be more useful when PTEN loss is deep or homogeneous.
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| Tumor Suppressor Genes in Prostate Cancer – Currently Prognostic, but Soon to Be Predictive?
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| Evan Yu, MD
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| PTEN, TP53, and RB1 alterations are currently best viewed as prognostic markers in prostate cancer, but they are increasingly shaping treatment choices as predictive data emerge. PTEN loss already has the strongest clinical signal, with AKT inhibition showing benefit in PTEN-deficient mHSPC, while compound tumor suppressor loss may also help identify patients more likely to benefit from chemotherapy, especially platinum-containing regimens.
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| Circulating Biomarkers for Prostate Cancer Precision Medicine - What Will Become Relevant in Daily Clinical Practice Soon?
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| Gerhardt Attard, MD, PhD, FRCP
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| Gerhardt Attard said the circulating biomarkers most likely to matter in everyday practice soon are serum PSA and plasma ctDNA, with ctDNA already useful for finding actionable alterations such as BRCA1/2, MSI/dMMR, or high tumor mutational burden. Dr. Attard stressed that these tests should be interpreted alongside disease burden and other clinical factors, because a good PSA response can still mean different things depending on whether the patient has low-volume or high-volume metastatic disease.
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