Bipolar androgen therapy for treatment of metastatic castration-resistant prostate cancer: A case series.

Advanced prostate cancer treatment has improved with androgen receptor signaling inhibitors (ARPI), yet many patients develop metastatic castration-resistant prostate cancer (mCRPC), characterized by sustained androgen receptor (AR) signaling.

Bipolar androgen therapy (BAT) introduces supraphysiologic testosterone levels to inhibit tumor growth, offering novel treatment for mCRPC by exploiting AR-dependent mechanisms.

Case 1: A 53-year-old man with mCRPC, post multiple systemic therapies, initiated BAT and pembrolizumab, achieving PSA reduction and improved quality of life before progression. The patient exhibited AR amplification, which may have contributed to favorable response to BAT. Case 2: A 73-year-old man with recurrent prostate cancer, stable on ADT and abiraterone, experienced PSA decline with BAT to an undetectable level, maintaining stability post-therapy discontinuation. Case 3: A 73-year-old man with metastatic prostate cancer, initially resistant to enzalutamide, achieved clinical benefit and disease control with BAT, although he did not meet PSA response criteria, patient had remarkable response upon enzalutamide rechallenge. Case 4: A 90-year-old man with localized prostate cancer, refractory to multiple treatments, experienced symptom relief and PSA reduction with BAT before progression.

BAT represents a promising treatment strategy for mCRPC. This case series underscores BAT's potential to induce significant clinical and biochemical responses, resensitize tumors to ARPIs, and improve patients' quality of life. Despite eventual progression in some cases, BAT offers a period of disease control. Further research is needed to optimize patient selection and understand the molecular determinants of BAT responsiveness.

ACKNOWLEDGMENTS

The authors would like to acknowledge the patients who are highlighted in this case report. ESA is partially supported by NCI Cancer Center Support Grant grant P30 CA077598 and DOD grant W81XWH‐22‐2‐0025.

A DEDICATION TO BRYCE OLSON

This case report is dedicated to the memory of Bryce Olson (1970 – 2023), an extraordinary patient advocate whose impact on the field of prostate cancer research and patient care cannot be overstated. Bryce's unwavering commitment to pushing the boundaries of medical science and his tireless advocacy for patients everywhere have left an indelible mark on our community. 

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A slice of happiness: Bryce and his beloved daughter Devona sharing memories on the slopes. Picture provided courtesy of Midori Karasawa.

Bryce possessed a rare magnetism that drew people together and catalyzed positive change. His voice empowered countless individuals to take an active role in their healthcare journeys, and his vision inspired researchers and clinicians alike to strive for excellence. Through his "Sequence Me" campaign, Bryce championed the use of genomic sequencing to guide personalized cancer treatments, encouraging patients to advocate for access to these innovative approaches.

Bryce's legacy is one of hope, perseverance, and the relentless pursuit of better outcomes for all patients. His advocacy extended beyond his own treatment, as he tirelessly worked to ensure that others could benefit from the latest advancements in precision medicine.

Though Bryce lost his battle with prostate cancer in July 2023, his spirit lives on in the work we continue and the lives he touched. We honor Bryce's memory by dedicating ourselves to the ideals he championed: patient empowerment, innovative research, and compassionate care.

May this case report serve not only as a contribution to medical knowledge but also as a testament to Bryce Olson's enduring influence and the profound difference one individual can make in the lives of many. Bryce, my friend, your legacy will forever live on. Your unwavering spirit, infectious optimism, and tireless dedication have left an indelible mark on our hearts and minds. The impact you've made in the lives of countless patients and in the field of cancer research will continue to ripple through time, inspiring generations to come. Your memory burns brightly in our hearts, guiding us forward in our pursuit of better care and brighter futures for all those facing cancer. We carry your torch with pride and determination, ensuring that your vision for patient empowerment and personalized medicine remains at the forefront of our mission.

The Prostate. 2024 Sep 22 [Epub ahead of print]

Elizabeth U Tran, Eric Ovruchesky, Kyra Yamamoto, Samantha Marley, Alexander Song, Elizabeth Pan, Aaron M Lee, Daniel Herchenhorn, Sam Denmeade, Emmanuel S Antonarakis, Mark Markowski, Rana R McKay

Moores Cancer Center, University of California San Diego, San Diego, California, USA., Instituto D'Or de Ensino e Pesquisa - IDOR, Rio de Janeiro, Brazil., Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA., Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA.