Topic: Metastatic Castration Resistant Prostate Cancer

The TRANSFORMER Study: Bipolar Androgen Therapy vs. Enzalutamide in Asymptomatic Men With mCRPC

E. David Crawford, MD, Editor-in-Chief of Grand Rounds in Urology and Professor of Urology at University of California, San Diego discusses the TRANSFORMER study and bipolar androgen therapy with Samuel R. Denmeade, MD, Professor of Oncology and Urology at Johns Hopkins University and co-leader of the Prostate Cancer Program for the Johns Hopkins Kimmel Cancer Center. Dr. Denmeade presents the study results, outlines the conceptual background, and notes the benefits of bipolar androgen therapy. TRANSFORMER compared enzalutamide with bipolar androgen therapy, a treatment in which testosterone levels are oscillated between low and high levels in order to prevent the adaptation of prostate cancer cells to a low-androgen environment. Results indicate that while bipolar androgen therapy may not have superior progression free survival rates when compared with enzalutamide, it can improve patient response to enzalutamide, suggesting that further research on sequential treatment is warranted. Notably, some men undergoing bipolar androgen therapy experienced a return in sexual function and also better physical functioning which contributed to improved quality of life.

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Castration Resistant Prostate Cancer – Developments and Challenges from 2020

In this Platinum Lecture, Emmanuel S. Antonarakis, MD, Professor of Oncology and Urology as well as Director of Prostate Cancer Medical Oncology Research and the Co-Director of the Prostate Cancer Multidisciplinary Clinic at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, summarizes developments from 2020 in mutation-targeted treatments for metastatic castration-resistant prostate cancer (mCRPC). He considers the successes of PARP inhibitors, especially for patients with the BRCA2 mutation, and the limitations of PD1 inhibitors. Dr. Antonarakis concludes by looking at promising research into B7-H3 and PSMA.

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Overall Survival with Sipuleucel-T in Patients Treated for Advanced Prostate Cancer

Rana R. McKay, MD, Associate Professor of Medicine at the University of California, San Diego, and Co-Leader of the Genitourinary Oncology Disease Team at the Moores Cancer Center, discusses the results of a study that compared the efficacy of first-line and any-line sipuleucel-T to that of novel hormonal agents in Medicare beneficiaries with metastatic castration-resistant prostate cancer (mCRPC). The intent of the study was to see how the use of sipuleucel-T, which has been available for just over a decade and was the first autologous vaccine approved for a solid tumor, might be impacted by the introduction of so many new therapies for mCRPC in the last 10 years. Dr. McKay explains that the results show that, for the population studied, use of sipuleucel-T, both as first-line and any-line therapy, results in a statistically significant improvement in overall survival compared to patients who never received sipuleucel-T and were instead treated with other novel hormonal agents. Following her presentation, E. David Crawford, MD, Editor-in-Chief of Grand Rounds in Urology, conducts a Q&A session with Dr. McKay in which they discuss the increasing acceptance of sipuleucel-T among medical oncologists, combination therapies with sipuleucel-T, and the future of sipuleucel-T, among other subjects.

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Management of mCRPC in China

Bo Dai, MD, PhD, Chief Physician and Director of the Department of Urology at Fudan University Shanghai Cancer Center, gives an overview of how metastatic castration-resistant prostate cancer (mCRPC) is managed in China. He explains that docetaxel, abiraterone, and enzalutamide are the only treatments available in China despite the proven effectiveness of other drug treatments. He references the PROfound study, which proved the effectiveness of olaparib, an FDA-approved drug which is available for metastatic ovarian cancer, but not mCRPC as of yet. Dr. Dai also reviews unmet treatment needs, including a lack of knowledge of the optimal treatment sequence, a need for overall survival improvement in the population of mCRPC patients in China, a lack of treatment urgency, and a lack of treatment affordability. He then shares data from Chinese studies on abiraterone and GT0918, which have both been found to produce positive results in patients. Dr. Dai concludes by discussing how abiraterone has become the most common mCRPC drug treatment due to it being produced in China.

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Recent Clinical Radionuclide Therapy Advances in mCRPC

Ulka Vaishampayan, MD, Professor of Oncology at Wayne State University and Chief of Solid Tumor Oncology at the Karmanos Cancer Center, discusses the phase 3 randomized controlled trial of 177-Lutetium-PSMA radionuclide therapy. In this brief summary, Dr. Vaishampayan discusses the mechanism of action of this novel therapy, how to identify patients utilizing a PSMA-based PET scan, and the inclusion/exclusion criteria from the phase 3 randomized control trial of this targeted agent.

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Genomic Markers and DNA Sequencing Testing

Daniel W. Lin, MD, reviews novel and emerging biomarkers across the spectrum of prostate cancer. He then explains an emerging model of prostate cancer treatment with genomic markers and DNA sequencing, discussing newly-identified precision targets and their therapeutic decision-making utility.

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Sequencing of Adjuvant Therapies

Daniel P. Petrylak, MD, provides his perspective on optimal drug sequencing for castration resistant prostate cancer (CRPC) and metastatic CRPC (mCRPC). He reviews the literature regarding available and emerging immunotherapeutic, hormonal, cytotoxic, and DNA damaging treatment options and when to time each drug.

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Integrating the AUA Guidelines into Your Practice

Michael S. Cookson, MD, MMHC, describes how urologists can use American Urological Association (AUA) guidelines to better manage metastatic castration resistant prostate cancer (mCRPC) patients. He stresses the importance of urologists serving as the primary caregiver, the multidisciplinary care model, and organized sequencing of treatments and therapeutics.

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Immunotherapy 101 for the Urologist

Raoul S. Concepcion, MD, summarizes the mechanism of action behind the immune response to cancer. He also provides an update on the current and emerging immunotherapies for cancer treatment, including vaccines, checkpoint inhibitors, CAR T-cell therapies, viral vectors, and adoptive cell therapy.

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Associate Editors


Mark A. Moyad, MD, MPH
University of Michigan
Ann Arbor, Michigan