How to cite: Treating Neuroendocrine Prostate Cancer. Grand Rounds in Urology. October 23, 2025. Accessed Apr 2026. https://grandroundsinurology.com/treating-neuroendocrine-prostate-cancer-2/
Summary
Oscar B. Goodman, Jr., MD, PhD, Medical Oncologist, Nevada Oncology Specialists, Las Vegas, Nevada, delivers a comprehensive, clinically grounded review of neuroendocrine prostate cancer, a rare but increasingly encountered and highly aggressive disease state that often emerges after prolonged androgen receptor pathway inhibition. Dr. Goodman outlines the clinical presentation, molecular biology, current treatment strategies, and future directions for both primary and treatment-related neuroendocrine prostate cancer.
He begins by defining neuroendocrine prostate cancer and distinguishing primary neuroendocrine disease from treatment-related neuroendocrine prostate cancer. Dr. Goodman emphasizes that treatment-related neuroendocrine prostate cancer is becoming more common, occurring in an estimated 20 to 30 percent of metastatic castration-resistant prostate cancer cases. These tumors often present with low prostate-specific antigen (PSA), rapid clinical progression, visceral metastases, lytic bone lesions, and elevated markers such as lactate dehydrogenase (LDH).
Pathologic subtypes are reviewed, including small cell carcinoma, large cell neuroendocrine carcinoma, mixed histologies, and adenocarcinoma with neuroendocrine differentiation. Prognosis is poor across most subtypes, with survival markedly inferior to that of typical adenocarcinoma.
Molecular characterization highlights recurrent loss of RB1, TP53, and PTEN, along with alterations in epigenetic regulators and DNA repair pathways. Dr. Goodman explains how deep androgen receptor suppression promotes lineage plasticity, leading to silencing of androgen signaling and activation of neuronal and neuroendocrine programs.
Current treatment options remain limited. Platinum-based chemotherapy combinations are the backbone of therapy, particularly in patients with aggressive variant prostate cancer molecular signatures. Data supporting the addition of carboplatin to cabazitaxel are reviewed, demonstrating a progression-free survival benefit in biomarker-selected patients. The presentation also reviews the role of immunotherapy in microsatellite instability (MSI)-high disease, poly (ADP-ribose) polymerase (PARP) inhibition in selected genomic contexts, and emerging targeted strategies.
Dr. Goodman shares future directions, including epigenetic modulation, prevention of lineage plasticity, and targeting DLL3 as a promising therapeutic avenue.
About the 28th Annual Southwest Prostate Cancer Symposium:
Presented by Program Chairs Nelson N. Stone, MD, Richard G. Stock, MD, and William K. Oh, MD, this conference educated attendees about advances in the management of localized and advanced prostate cancer, with a focus on imaging, technology, and training in the related devices. It included a scientific session, as well as live demonstrations of surgical techniques. You can learn more about the conference here.
ABOUT THE AUTHOR
Oscar B. Goodman Jr., MD, PhD, is a physician-scientist and genitourinary oncologist who has been practicing as a hematologist, medical oncologist, and clinical researcher in Las Vegas since 2007, joining Nevada Oncology Specialists in early 2025. He participates in basic, translational, and clinical research studies. His translational research interests center on understanding the mechanisms that govern prostate cancer’s therapeutic resistance. He has authored numerous abstracts, book chapters, and more than 50 peer-reviewed publications. He has also received peer-reviewed prostate cancer research support through the Department of Defense.
