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Urology News and Education Resource
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Wednesday, 03 June 2026 |
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From the Desk of Evan Yu: “PARP with PD-1/PD-L1 inhibition. Is there any magic to the combination in a molecularly unselected patient population?”
Evan Yu, MD
The recent KEYNOTE-365 presentation at the 2019 Genitourinary Multidisciplinary Symposium reported on 42 previously docetaxel-treated metastatic castration-resistant prostate cancer patients who underwent combination pembrolizumab 200 mg intravenously every 21 days with olaparib 400 mg orally twice daily. In this trial, Guardant360® was utilized to evaluate circulating tumor DNA for BRCA1, BRCA2 or ATM alterations.
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Keynote-365: Pembrolizumab Plus Olaparib in Docetaxel Pretreated Patients with Metastatic Castrate-resistant Prostate Cancer
It has been previously shown that treatments for metastatic castrate-resistant prostate cancer such as docetaxel and enzalutamide may increase programmed death ligand 1 (PD-1) expression. KEYNOTE-365 is a non-randomized, open-label phase 1b/2 umbrella trial evaluating the safety and efficacy of three treatment combinations in patients who have progressed on second-generation hormonal therapy and chemotherapy: Cohort A: pembro + olaparib, Cohort B: pembro + docetaxel + prednisone, Cohort C: pembro + enzalutamide. The study start date was in 2016 and it is projected to come to completion in 2022. Dr. Evan Yu presented the early results from Cohort A combining pembro + olaparib.
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| Rapid Abstract Session: Prostate Cancer |
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Results of a 50 Patient Single-Centre Phase II Prospective Trial of Lutetium-177 PSMA-617 Theranostics in mCRPC
PSMA is over-expressed in all prostate tissue, including prostatic carcinoma. Lutetium-177 (177Lu)-PSMA617 (LuPSMA) is a small radiolabeled molecule which binds to PSMA and delivers a dose of β radiation. The authors of this study have previously reported on their experience of 30 men with metastatic CRPC treated in a single-center phase II prospective trial of LuPSMA. This abstract represents an updated analysis of an extended cohort of 50 patients.
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TALAPRO-2: A Two-Part, Placebo-Controlled Phase III Study of Talazoparib with Enzalutamide in Metastatic Castration-Resistant Prostate Cancer
Enzalutamide is an androgen-axis targeted therapy with established efficacy in the treatment of advanced prostate cancer, including metastatic castration-resistant and non-metastatic CRPC. TALA is a poly (ADP-ribose) polymerase (PARP) inhibitor that inhibits PARP1/PARP2 and traps PARP on DNA, preventing DNA damage repair, and causing cell death in BRCA1/2-mutated cells. In this study, Dr. Agarwal and colleagues examine the combination of TALA with ENZA in mCRPC, with the expectations that it may improve clinical outcomes, based on the strength of prior studies. They describe their proposed 2-part trial.
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The CHEIRON Study: Docetaxel plus Enzalutamide versus Docetaxel as First Line Chemotherapy for Patients with mCRPC
Docetaxel and enzalutamide have previously been demonstrated to be effective in the treatment of metastatic castrate resistant prostate cancer (mCRPC). In this multi-institutional, Italian study, it was theorized that combination therapy would increase efficacy as first line therapy in patients with mCRPC.
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Cost-Effectiveness of Metastasis-Directed Therapy in the Setting of Oligometastatic Hormone-Sensitive Prostate Cancer
Dr. Parikh discussed previously published data which suggested there may be an outcome benefit for treatment of oligometastatic disease in patients with hormone sensitive prostate cancer. The group constructed a Markov model to compare costs and outcomes of 3 treatment strategies: Metastasis directed therapy with upfront stereotactic body radiation therapy Abiraterone + ADT utilizing data from STOMP, STAMPEDE M1 sub-analysis, and STAMPEDE overall. This study then performed a cost effectiveness analysis comparing ADT compared to MDT followed by salvage ADT in patients with asymptomatic hormone sensitive oligometastatic prostate cancer.
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Genomic Drivers of Poor Prognosis and Enzalutamide Resistance in Metastatic Castration-Resistant Prostate Cancer
Recent studies have identified genomic alterations in metastatic castrate-resistant prostate cancer (mCRPC), but our understanding of the clinical implications is in its infancy. As part of the multi-institiutional West Coast Prostate Cancer Dream Team project, Chen et al. conducted a prospective cohort study. Using whole genome sequencing (WGS), they analyzed associations between “key” gene alterations and overall survival. They also performed whole-transcriptome RNA sequencing to identify genomic associations with enzalutamide resistance in mCRPC.
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Updated Analysis of Progression-Free Survival with First Subsequent Therapy and Safety in the SPARTAN Study of Apalutamide in Patients with High-Risk Nonmetastatic Castration-Resistant Prostate Cancer
The SPARTAN study is a multicenter, randomized, double-blind, placebo-controlled Phase 3 trial investigating the safety and efficacy of apalutamide (APA) in men with high-risk non-metastatic castration-resistant prostate cancer (nmCRPC). Patient accrual began in 2013 and the study is estimated to conclude in 2021. Patients with nmCRPC were randomized to APA + androgen deprivation therapy (ADT) or placebo (PBO) + ADT. Initial analysis showed a decreased risk of metastasis by 72% (HR 0.28, p< 0.0001) in the experimental group. Dr. Small presented findings after an additional year of follow-up.
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| Collaborative Management of Oligometastatic and Recurrent Prostate Cancer - Tumor Board |
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A Medical Oncologist Perspective by Silke Gillessen, MD
Dr. Silke Gillessen provided one of two of the medical oncologist perspectives in the Oligometastatic Disease Tumor Board. She referenced the GETUG-12 trial which randomized high-risk prostate cancer patients to either ADT for three years, with a local treatment at three months and the addition of docetaxel for four cycles, or to ADT with local treatment only and gave her opinion on systemic therapy for this patient in the tumor board.
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A Medical Oncologist Perspective by Michael Morris, MD
Dr. Michael Morris gave the second medical oncologist perspectives in the Oligometastatic Disease Tumor Board. He began with the prognosis that cancer-specific survival of patients with positive surgical margins, and even 3-4 positive nodes are objectively not as bad as originally thought.
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A Urologic Oncologist Perspective by Edward Schaeffer, MD
Dr. Schaeffer provided the urologic oncologist perspective in the Oligometastatic Disease Tumor Board. He began discussing the biopsy strategy of such a patient, referencing the PRECISION trial and the option of radical prostatectomy for this patient. He also discussed pelvic lymph node dissection and the functional impact of postoperative radiotherapy.
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A Radiation Oncologist Perspective by Bridget Koontz, MD
Dr. Bridget Koontz provided one of the radiation oncologist perspectives in the Oligometastatic Disease Tumor Board. She discussed the role of external beam radiation therapy (EBRT) in positive node disease and several trials showing a benefit to EBRT + ADT over EBRT alone in patients with positive node disease.
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A Radiation Oncologist Perspective by Gert de Meerleer, MD
Dr. Gert de Meerleer provided the second radiation oncologist perspectives in the Oligometastatic Disease Tumor Board. He began his presentation with his recommended staging imaging tests for prostate cancer patients.
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