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PEER-TO-PEER CLINICAL CONVERSATIONS
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Debating Prostate Radiotherapy for Metastatic Hormone-Sensitive Prostate Cancer
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Tyler Seibert, MD, PhD
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| Tyler Seibert outlines his approach to radiation therapy for the primary tumor in metastatic hormone-sensitive prostate cancer. He summarizes three randomized trials that consistently show a progression-free survival benefit, particularly in patients with low-volume metastatic disease.
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The 2026 Advanced Prostate Cancer Consensus Conference
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| In mHSPC Trials, What Are Relevant Endpoints from a Clinical Point of View?
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| Ian Davis, MBBS(Hons), PhD, FRACP
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| Ian Davis emphasized that the most meaningful mHSPC trial endpoints are the ones that reflect real patient benefit, especially overall survival, disease-specific survival, toxicity, and patient-reported outcomes. He also cautioned that some commonly used surrogate or timing-based endpoints may be useful for trial design, but they do not always translate cleanly into what matters most in clinical care.
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| What Role Does Quality of Life Play in This Setting?
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| Yüksel Ürün, MD, PhD
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| Yüksel Ürün emphasized that in mHSPC, quality of life should be measured directly rather than assumed, because longer survival also means longer exposure to treatment toxicities. He highlighted the “toxicity paradox” of modern intensification and argued for routine use of patient-reported outcomes, frailty assessment, and digital tools to tailor treatment intensity while preserving function, independence, and well-being.
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| Which Patients Should Receive "TRIPLET and More" Systemic Therapy for mHSPC
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| Karim Fizazi, MD, PhD
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| Karim Fizazi argued that triplet therapy is most compelling for fit men with de novo mHSPC, especially those with high-volume or biologically aggressive disease, because it has delivered the strongest overall survival gains seen so far in this setting. He also stressed that biology matters, so biomarkers such as BRCA, PSMA, and PTEN may eventually help select patients most likely to benefit, while relapsing low-volume mHSPC may be less suitable for triplet treatment.
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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 argued that doublet systemic therapy is the right choice for many mHSPC patients, especially those who are BRCA wild type, PTEN competent, PSMA negative, and have low-volume metachronous disease. He emphasized that shared decision-making matters because triplet therapy is not yet proven superior for every patient, and biomarkers or early PSA response may help identify who can reasonably stay with doublet therapy.
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| rPFS as a Surrogate for Hard Endpoints in mHSPC: Evidence and Regulatory Implications
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| Susan Halabi, PhD, FSCT, FASA, FASCO
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| Susan Halabi said radiographic progression-free survival is a useful but only partially validated surrogate for overall survival in mHSPC, with the strongest evidence in ADT-based trials and weaker support in ARPI-containing regimens. Her main message was that OS confirmation still matters, and regulatory acceptance of rPFS depends on treatment context, follow-up maturity, and post-progression therapy patterns.
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| Radiation Therapy of the Primary in Patients with mHSPC
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| Tyler Seibert, MND, PhD
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| Tyler Seibert reviewed the evidence supporting radiotherapy to the prostate in mHSPC, especially for low-burden disease where trials like STAMPEDE and meta-analyses show the clearest benefit. His key message was to treat the primary in low-volume conventional-imaging mHSPC, while in higher-burden disease the decision is more selective and depends on metastatic extent, symptoms, and response to systemic therapy.
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| Optimal Management of Synchronous Oligometastatic HSPC on PSMA PET
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| Piet Ost, MD, PhD
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| Piet Ost framed synchronous PSMA PET oligometastatic HSPC as a biologically distinct state that changes how we think about “M0” and low-volume “M1” disease. He argued for systemic intensification in higher-risk patients, prostate radiotherapy for low-volume disease, and said metastasis-directed therapy is still investigational in synchronous disease and should ideally be studied in trials like STAMPEDE2.
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| Optimal Management of Metachronous Oligometastatic HSPC on PSMA PET
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| Nicholas van As, MD, MBBCH
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| Nicholas van As argued that PSMA PET has made metachronous oligometastatic HSPC more precise to define and should guide how much local and systemic therapy is used. He emphasized that PSMA PET-informed metastasis-directed therapy can delay progression and ADT in selected patients, but management should still be individualized based on PSA doubling time, disease burden, and biology, with systemic intensification reserved for higher-risk cases.
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| Considerations for Selection of ARPIs in Older Patients with mHSPC
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| Dana Rathkopf, MD
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| Dana Rathkopf emphasized that ARPI choice in older men with mHSPC should be based on physiologic age, frailty, comorbidity, cognition, and drug-specific toxicity rather than age alone. She highlighted that most fit older patients still benefit from treatment intensification, but the balance of benefit and risk becomes more individualized in vulnerable or frail patients, with darolutamide often favored when CNS toxicity or drug interactions are a concern.
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