Targeting the AR: Have We Reached the Outer Limits?

Charles Ryan | February 05, 2020

In the summary slide of one of my 'go-to' talks I pose the question “Have we reached the limits of androgen receptor (AR) targeting?”. Of course, I don’t know the answer, which is precisely why it is framed in the form of a question on a summary slide. But I think about it a lot. So, let’s ponder this question a little.

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Dr. Charles J. Ryan, MD

Charles J. Ryan, MD is the B.J. Kennedy Chair in Clinical Medical Oncology at the University of Minnesota and Director of the Division of Hematology, Oncology and Transplantation. He previously held the position of Professor of Clinical Medicine and Urology and the Clinical Program Leader for Genitourinary Medical Oncology at the UCSF Helen Diller Family Comprehensive Cancer Center

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Everyday Urology - Oncology Insights
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By Sanjeev Kaul, MD, MCh
During much of the past 30 years, genetic tests for heritable disorders have assessed limited numbers of genes and have often employed serial testing algorithms in which the next test was determined by the results of the prior test.¹ The advent of next-generation (also known as massively parallel high-throughput) sequencing has transformed this picture by making it possible to sequence the entire human genome for less than $1,000.1,2
By Fred Saad, MD, FRCS
Summary

Protecting and improving bone health is critical when managing all stages of prostate cancer. Androgen deprivation therapy (ADT) accelerates bone resorption, which compromises bone mass and integrity starting early in treatment.1 Metastatic prostate cancer is associated with a marked increase in risk of skeletal events (fracture, spinal cord compression, and bone surgery or radiotherapy) associated with both bone metastases and treatment-induced bone loss.
By Charles J. Ryan, MD.
The European Association of Urology defines castration-resistant prostate cancer (CRPC) as serum testosterone < 50 ng/dL or < 1.7 nmol/L plus either biochemical progression (three consecutive rises in prostate-specific antigen [PSA] one week apart, resulting in two 50% increases over the nadir, and PSA > 2 ng/mL) or radiologic progression
By Fred Saad, MD, FRCS
Until 2010, our treatment armamentarium for prostate cancer (PC) was fairly limited. Patients received local therapy for non-metastatic disease, androgen deprivation therapy (ADT) for hormone-naïve metastatic disease, denosumab and zoledronic acid for metastatic castration-resistant prostate cancer (mCRPC), and bisphosphonates or docetaxel for symptomatic mCRPC.
By Evan Yu, MD and Sumanta Kumar Pal, MD
As we counsel our patients about the importance of clinical research, there are two key messages to send. The first is that without clinical trials, we would not have access to the large number of life-prolonging therapies that we have for genitourinary cancers and others. That translates into more family trips, birthday parties, time spent with grandchildren and graduations attended.
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Written by Zachary Klaassen, MD, MSc and Christopher J.D. Wallis, MD, PhD
January 6, 2020

Several trials have recently focused on delineating the optimal radiotherapy fractionation schedule for the primary treatment of prostate cancer. In 2016, efficacy results of the Dutch HYPRO trial were published, assessing hypofractionated radiotherapy compared 


Written by Hanan Goldberg, MD
November 19, 2019
In the previous review article (“First-line treatment of metastatic castrate-resistant prostate cancer”), metastatic castrate-resistant prostate cancer (mCRPC) and its approved first-line treatment options were elaborated.
Written by Hanan Goldberg, MD
November 19, 2019
In 2019 Prostate cancer (PCa) accounts for nearly 1 in 5 new diagnoses of cancer in men in the USA.1 In the last several years the overall prostate cancer (PCa) incidence rate declined by approximately 7% per year.
Written by Hanan Goldberg MD, Department of Urology, SUNY Upstate Medical University, Syracuse, NY, USA
January 22, 2020
Prostate cancer (PCa) is the second most common form of cancer diagnosed in US men. It represents 19% of newly diagnosed cancers, and the third leading cause of cancer death, accounting for an estimated 39,430 deaths in 2018.1
Written by Zachary Klaassen, MD
April 16, 2019
In 2018 in the United States, there will be an estimated 164,690 new cases of prostate cancer (19% of all male cancer incident cases, 1st) and an estimated 29,430 prostate cancer mortalities (9% of all male cancer deaths, 2nd only to lung/bronchus cancer).
Conference Coverage
Recent data from conferences worldwide
Presented by Eleni Efstathiou, MD, PhD
Barcelona, Spain (UroToday.com) Following oral presentation of the PROfound study of olaparib in metastatic castration-resistant prostate cancer (mCRPC) patients with selected homologous recombination repair defects in their tumors, Dr. Eleni Efstathiou discussed the findings and posed the question of whether this study should be considered practice-changing.
Presented by Ronald De Wit, MD, PhD
Barcelona, Spain (UroToday.com) Multiple therapeutic options have been approved for the treatment of men with metastatic castration-resistant prostate cancer (mCRPC), including the second-generation anti-androgens abiraterone and enzalutamide, and chemotherapy with docetaxel or cabazitaxel.
Presented by Maha Hussain, MD
Barcelona, Spain (UroToday.com) Though significant progress has been made in elucidating molecular alterations in metastatic castration-resistant prostate cancer (mCRPC), no biomarker-selected targeted therapeutic options have existed in this disease until today. Dr. Hussain and colleagues presented an analysis of the PROfound study
Presented by Nicholas James, MBBS, PhD
Barcelona, Spain (UroToday.com) Multiple studies have shown the efficacy of docetaxel in metastatic hormone-sensitive and castration-resistant prostate cancer, though there is ongoing debate regarding the impact that metastatic disease burden has on docetaxel use in the hormone-sensitive setting. 
Presented by Karim Fizazi, MD, PhD
Barcelona, Spain (UroToday.com) Relative to other solid tumors, prostate cancer is viewed as an immunologically “cold” tumor with less robust responses to immunotherapy than other diseases such as melanoma or lung cancer.
Presented by Wassim Abida, MD, PhD
Barcelona, Spain (UroToday.com) Rucaparib is a PARP inhibitor and has shown antitumor activity in patients with mCRPC and a deleterious DNA damage repair-deficient gene alteration. 
Presented by Matthew R. Smith, MD, PhD
Barcelona, Spain (UroToday.com) Patients with metastatic castration-resistant prostate cancer (mCRPC) and disease progression after androgen receptor (AR) targeted therapy and taxane-based chemotherapy have a poor prognosis and few options for treatment.
Presented by Robert Van Soest, MD, PhD
Barcelona, Spain (UroToday.com) Dr. Robert Van Soest presented on the recent advances in the treatment of castrate-resistant prostate cancer (CRPC). The current therapeutic options in metastatic hormone-sensitive prostate cancer (mHSPC), and the 1st and 2nd treatment lines of metastatic CRPC. Recently, there is randomized prospective data comparing various treatments in metastatic CRPC patients. One example is a study comparing cabazitaxel to abiraterone or enzalutamide in metastatic CRPC patients
Presented by Noel Clarke, MD
Barcelona, Spain (UroToday.com) PARP inhibitors have been increasingly recognized for their potential therapeutic role in patients with advanced prostate cancer, particularly in the setting of DNA repair defects. Prior work by Dr. Clarke and colleagues demonstrated, in a phase II clinical trial, that olaparib in combination with abiraterone significantly prolonged radiologic progression-free survival compared with abiraterone alone) in patients with mCRPC in the second-line metastatic setting who received prior docetaxel.1
Presented by Christopher P. Evans, MD, FACS
Barcelona, Spain (UroToday.com) Review of some of the most important studies in the castrate-resistant prostate cancer space published in the past year. First, from ESMO 2018, in a phase 3 randomized controlled trial, radium 223 with abiraterone (ERA 223) did not demonstrate improved symptomatic skeletal-related event-free or overall survival compared to abiraterone with placebo. Clinical fractures were more common in the abiraterone and radium group. Based on the data from the study, the use of radium 223 in combination with abiraterone was not recommended. 
Presented by Kim N. Chi, MD
San Francisco, CA (UroToday.com) The LATITUDE study,1 published in July 2017, was a phase III randomized, clinical trial that evaluated the efficacy of abiraterone acetate and prednisone with androgen deprivation therapy (ADT) in men with newly-diagnosed, castration sensitive, metastatic prostate cancer. 1199 men were randomized to receive ADT with abiraterone and prednisone, versus ADT with dual placebos.
Presented by David F. Jarrard, MD
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