Video

Metastatic Castrate Resistant Prostate Cancer – Immunotherapy and PARP Inhibitors

Alan Tan, MD, discusses multiple advanced treatment options for prostate cancer, focusing on genomic testing, PARP inhibitors, and emerging immunotherapy strategies. His 26-minute presentation begins with data indicating that 12% of prostate cancer patients carry germline mutations, predominantly in the BRCA family, emphasizing the prognostic significance of BRCA alterations. Genomic testing advancements, particularly in homologous recombination repair (HRR) alterations, reveal actionable pathways in approximately 25-27% of cases. PARP inhibitors are highlighted for their efficacy in BRCA-mutated cancers, with the latest trials—PROpel, TALAPRO-2, and MAGNITUDE—demonstrating survival benefits in combination therapies.

Dr. Tan also addresses immunotherapy, with a compelling clinical example underscoring the transformative impact of pembrolizumab in an ultra-high tumor mutation burden case. He also examines T-cell engagers, which show promise in overcoming downregulated MHC expression, and early-phase trials for bispecific antibodies. Toxicity management in PARP inhibitors is discussed in detail.

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Optimal Management of Biochemically Recurrent Nonmetastatic Prostate Cancer

Aaron Berger, MD, delves into the evolving landscape of non-metastatic castration-sensitive prostate cancer (nmCSPC) and high-risk biochemical recurrence, focusing on diagnostic and therapeutic updates. In this 7-minute presentation, Dr. Berger emphasizes advanced imaging, particularly PSMA PET scans, as the diagnostic standard due to its superior sensitivity over conventional CT and bone scans.

Dr. Berger discusses treatment strategies, including salvage radiation therapy and the use of androgen deprivation therapy (ADT). For radiation-treated patients, focal salvage therapies, including cryoablation, HIFU, and electroporation, are discussed as options. The presentation underscores the shrinking non-metastatic space due to advancements in imaging technology that now frequently identify micrometastases.

Dr. Berger reinforces the importance of genetic testing and surveillance protocols involving regular PSA monitoring and imaging triggered by symptoms or PSA progression. He highlights the dynamic shifts in prostate cancer management, driven by improved diagnostics and the integration of advanced systemic therapies within an increasingly precise treatment paradigm.

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Oligometastatic Prostate Cancer

Daniel Song, MD, explores the evolving role of metastasis-directed therapy (MDT) and androgen deprivation therapy (ADT) in oligometastatic prostate cancer. Initial studies, including SABR-COMET and STOMP, demonstrate that MDT, through approaches like stereotactic body radiotherapy (SBRT) or surgery, improves progression-free and ADT-free survival compared to observation alone. Recent trials also evaluate the combination of MDT and short-term ADT, such as the EXTEND trial, which shows significantly prolonged progression-free survival.

The 9-minute presentation highlights how advanced imaging, particularly PSMA PET scans, outperforms conventional imaging in detecting and targeting metastases, enhancing MDT’s efficacy. Comparisons of PSMA-guided versus choline-guided SBRT reveal superior outcomes in disease-free survival. Furthermore, ongoing research seeks to clarify whether systemic hormone therapy is necessary alongside MDT, with trials like DART exploring novel ADT strategies.

Dr. Song asserts that MDT improves survival metrics in oligometastatic prostate cancer, particularly when informed by advanced imaging. Combining MDT with prostate radiation or systemic ADT offers additional survival benefits.

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Clinical Trials in MIBC and NMIBC

Daniel P. Petrylak, MD, discusses advancements in treating urothelial carcinoma, emphasizing innovative therapies for BCG-refractory, recurrent, and metastatic disease.

In this 10-minute talk, Petrylak highlights Dr. Neil Shore’s INSTIL trial, a significant phase 3 study evaluating the adenovirus interferon agent nadofaragene firadenovec. Dr. Petrylak also discusses how immune checkpoint inhibitors, such as pembrolizumab, are moving into early-stage treatment and combined with BCG for non-cystectomy patients.

The discussion transitions to innovative drug delivery systems, such as a “pretzel” device designed for intravesical drug release.
Dr. Petrylak shares new trials in treating metastatic carcinoma that focus on minimizing side effects linked to conventional drugs like enfortumab vedotin by introducing smaller, less immunogenic agents. These trials, including a DEVAL phase 1 dose-escalation study, underscore the importance of these targeted innovations in battling this challenging cancer.

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Metastatic Castrate Sensitive Prostate Cancer

Rana McKay, MD, discusses the evolving treatment strategies for metastatic hormone-sensitive prostate cancer (mHSPC), emphasizing advancements over the past decade. In this 20-minute presentation, McKay shares that prostate cancer remains a leading cause of mortality among men. While traditional androgen deprivation therapy (ADT) has long been the cornerstone treatment, newer approaches integrating chemotherapy, androgen receptor signaling inhibitors (ARSIs), and combination regimens have transformed patient outcomes. She refers to landmark studies like CHARTED, LATITUDE, and STAMPEDE, highlighting the benefits of early intensifying treatment and showing significant survival advantages with doublet and triplet therapies. She also shares recent trials, including PIECE-1 and ARASENS, that underscore the effectiveness of adding agents like abiraterone or darolutamide to ADT and docetaxel for high-risk, high-volume disease.

Dr. McKay asserts clinical decision-making now incorporates disease factors such as volume and risk, patient comorbidities, and drug-specific considerations like toxicity profiles and cost. Emerging genomic and molecular tools are poised to refine treatment personalization further, with ongoing trials exploring the optimal integration of novel agents.

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