International Prostate Cancer Update Archives

Theranostics & Radiopharmaceutical Trials

Posted by Daniel P. Petrylak, MD | Jul 2020

Daniel P. Petrylak, MD, Director of Genitourinary Oncology, Professor of Medicine and Urology, Co-Leader of Cancer Signaling Networks, and Co-Director of the Signal Transduction Program at Yale University Cancer Center, reviews several studies in which radium-223 is used both alone and in combination with other treatments for prostate cancer. Since radium-223 is an alpha particle, it requires fewer hits to damage DNA, offering an advantage over beta particles. Dr. Petrylak further explains the benefits of theranostics which deliver isotopes directly to the tumor site. He concludes that radium-223 is effective in treating metastatic castration-resistant prostate cancer (mCRPC), but cautions that until potential toxicity levels are better understood, combining radium-223 with either abiraterone or prednisone is not advised.

GRU Challenging Case: Androgen Deprivation Therapy

Posted by Neal D. Shore, MD | Jul 2020

Neal D. Shore, MD, FACS, Medical Director for the Carolina Urologic Research Center, discusses the physiological and economic factors impacting the ADT selection process. He particularly emphasizes the impact of the current volume-based and economically incentivized model of treatment and how this can restrict urologists. He also discusses the physiological impacts of drug-drug interactions, alternate modes of administration, and the complex prospect of an oral alternative.

A Better Abiraterone: The Backdoor Pathway for Intracrine Androgen Metabolism

Posted by James L. Mohler, MD | Jul 2020

James L. Mohler, MD, Associate Director and Senior Vice President for Translational Research and Professor of Oncology at Roswell Park Comprehensive Cancer Center in Buffalo, New York, discusses the cause of and potential solutions to androgen receptor expression in castration-recurrent prostate cancer. He explains that prostate cancer tissue in a patient with castration-recurrent disease actually has greater levels of testosterone than benign prostate tissue and that castration-resistant prostate cancer relies on a backdoor pathway of manufacturing testosterone by which dihydrotestosterone (DHT) is made from androstanediol. Abiraterone is intended to inhibit CYP17A1 and therefore prevent the manufacture of DHT, but Dr. Mohler suggests that abiraterone inhibits CYP17A1 that is too far from DHT synthesis to achieve long term response by inhibition. He then discusses current research about a promising drug that targets the catalytic domain shared by the five 3α-oxidoreductases associated with DHT production.

Molecular Imaging For Staging and Advanced Disease – Axumin and PSMA

Posted by Robert E. Reiter, MD, MBA | Jun 2020

Robert E. Reiter, MD, Bing Professor of Urology and Molecular Biology, Director of the Prostate Cancer Program, and Director of Urologic Research at the David Geffen School of Medicine at the University of California, Los Angeles, discusses the benefits of PSMA imaging in the context of biochemical recurrence. He reviews data from an Australian and an American study which both depict a positive correlation between PSA levels and PSMA prostate cancer detection rates, as well as high sensitivities for detection of recurrence based on pathologic confirmation. He then discusses the results of a study which compared PSMA with Axumin and found PSMA to be more than twice as effective in all areas but the prostate bed, which is most likely due to PSMA being excreted through the bladder. He argues that PSMA imaging can produce between a 29% and 76% change in prostate cancer management and allows for greater precision in treatment, resulting in fewer occurrences of unnecessary radiation therapy and long term systemic therapy.

Chemotherapy Trials

Posted by Daniel P. Petrylak, MD | Jun 2020

Daniel P. Petrylak, MD, Director of Genitourinary Oncology, Professor of Medicine and Urology, Co-Leader of Cancer Signaling Networks, and Co-Director of the Signal Transduction Program at Yale University Cancer Center in New Haven, Connecticut, discusses data from recent chemotherapy trials for castrate-resistant prostate cancer (CRPC). Dr. Petrylak specifically examines trials evaluating drug combinations as treatment for CRPC patients. Additionally, he reviews the effectiveness of PARP inhibitors in patients with DNA repair mutations. Finally, he notes the apparent superiority of cabazitaxel to NG AA treatment after progression on docetaxel.