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Advances in Treatment for Metastatic Hormone Sensitive Prostate Cancer: With So Many Options, Can We Really Go Wrong?

Alicia Morgans | September 05, 2019

As we all look forward to another prostate cancer awareness month, I find myself reeling with the advances the field has seen in the past year, particularly in the area of hormone sensitive metastatic prostate cancer. We learned that men may live longer if we can radiate the primary tumor if they have low volume metastatic disease. We also learned that enzalutamide and

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Alicia Morgans, MD

Alicia Morgans, MD, MPH Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts. She is a clinician and physician investigator specializing in investigating complications of systemic therapy for prostate cancer survivors. She has expertise in clinical trials and patient-reported outcome measures, and as well as incorporating patient preferences and beliefs into clinical decision making.

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Written by Zachary Klaassen, MD, MSc, and Christopher J.D. Wallis, MD, Ph.D
November 19, 2019

In the United States and Europe, prostate cancer is the second most common malignancy and the second leading cause of cancer mortality among men1. While approximately 3% of men in the United States present with metastatic disease2, higher rates are experienced globally3. 

 

Written by Hanan Goldberg MD, Department of Urology, SUNY Upstate Medical University, Syracuse, NY, USA
February 1, 2020
Prostate cancer (PCa) is the most common non-cutaneous malignancy in US men and the second most common cause of cancer-specific death.1 The American Cancer Society estimates that in 2019, approximately 174,650 new cases will be diagnosed, and 31,620 cancer-specific deaths will occur.2
Written by Zachary Klaassen, MD, MSc
April 16, 2019
Metastatic hormone-sensitive prostate cancer (mHSPC) is the disease space whereby men have metastatic prostate cancer and have never received (ie. are sensitive to) androgen deprivation therapy (ADT). mHSPC previously constituted ~30% of prostate cancer cases,1 however, from 2004-2012 secondary to PSA testing, the estimate was ~5% of cases.2
Conference Coverage
Conference Highlights Written by Physician-Scientist
Presented by Nick James, MBBS, PhD, and Bertrand Tombal, MD, PhD
In this session, Dr. Bertrand Tombal and Dr. Nick James summarized the panel responses to the consensus questions. This was followed by a discussion on the management of metastatic hormone sensitive prostate cancer (mHSPC) with input from the discussants and the panel.
Presented by Ian Davis, MBBS, PhD, FRACP, FAChPM
In this session, Dr. Ian Davis reviewed the evidence for “triplet therapy” comprising ADT plus docetaxel plus additional systemic therapy in metastatic hormone sensitive prostate cancer (mHSPC).
Presented by Karim Fizazi, MD, PhD
In this session, Dr. Karim Fizazi reviewed evidence for “triplet therapy” comprising ADT plus radiation (RT) to the primary plus additional systemic therapy in metastatic hormone sensitive prostate cancer (mHSPC).
Presented by Karim Fizazi, MD, PhD
In this presentation, Dr. Karim Fizazi discussed updated results of PEACE-1, a randomized Phase 3 trial in men with de novo metastatic castration-sensitive prostate cancer (mCSPC). This update focused on the overall survival (OS) for men treated with or without abiraterone plus prednisone (AAP).
Presented by Andrew J. Armstrong, MD
(UroToday.com) In the Proffered Paper Session of the ESMO Annual Congress focusing on prostate cancer, Dr. Andrew Armstrong presented the final overall survival analysis from the ARCHES trial of enzalutamide in men with metastatic hormone-sensitive prostate cancer (mHSPC).
Presented by Peter J. Goebell, MD, PhD
The ESMO 2021 virtual annual meeting’s prostate cancer session included a presentation by Dr. Peter Goebell discussing real-world treatment patterns among patients with metastatic hormone-sensitive prostate cancer (mHSPC).
Presented by Daniel J. George, MD
The ESMO 2021 annual meeting’s prostate cancer session included a presentation by Dr. Daniel George presenting data assessing real-world utilization of advanced therapies by metastatic site and age among patients with metastatic castration-sensitive prostate cancer (mCSPC).
Presented by Christopher Sweeney, MBBS
The treatment for metastatic hormone-sensitive prostate cancer plenary session at the EAU 2021 Annual Meeting included a presentation by Dr. Christopher Sweeney discussing when and how to use systemic treatment for recurrent metastatic hormone-sensitive prostate cancer (mHSPC).
Presented by Declan Murphy, MB, BCH, BaO, FRACS, FRCS
At the European Association of Urology (EAU) 2021 Annual Meeting’s plenary session on the treatment for metastatic hormone-sensitive prostate cancer, Dr. Declan Murphy presented a state of the art lecture on the role of modern imaging for de novo versus recurrent metastatic hormone-sensitive prostate cancer (mHSPC).
Presented by Lisa Horvath, PhD, MBBS, FRACP
 In this summary of the preceding three presentations, Dr. Lisa Horvath showed where each abstract falls within the natural history of prostate cancer. Regarding the first presentation, data on radiographic progression free survival (rPFS) with the addition of abiraterone in de novo mHSPC from the PEACE-1 study, 
Presented by Umang Swami, MD
At the 2021 ASCO Annual Meeting, Dr. Umang Swami and colleagues assessed the real-world utilization of effective combination therapies as first-line treatment in insured patients in the U.S. with mCSPC. The authors performed a retrospective study of the Optum health insurance claims database, which includes patients claims data from both commercially insured and Medicare Advantage populations. 
Presented by Daniel J. George, MD
There are a number of treatment options that have been shown to improve overall survival in mCSPC, including docetaxel and novel hormonal therapies including abiraterone acetate, enzalutamide, and apalutamide. While these agents have proven beneficial in clinical trials, improvement in population-level outcomes depends on their widespread adoption. 
Presented by Stephen J. Freedland, MD
There are a number of treatment options that have been shown to improve overall survival, including docetaxel and novel hormonal therapies including abiraterone acetate, enzalutamide, and apalutamide. While these agents have proven beneficial in clinical trials, improvement in population-level outcomes depends on their widespread adoption. Dr. Freedland presented results of an analysis of Medicare data regarding real-world utilization of these agents in men with mCSPC.
Presented by Andrew J. Armstrong, MD
The phase III ARCHES trial, along with the ENZAMET trial, provided the basis for enzalutamide’s approval in this disease space. However, data from each of these trials have suggested that the benefit of treatment intensification may differ on the basis of disease extent. To explore this further, 
Presented by Arun Azad, MBBS, PhD, FRACP
Enzalutamide plus ADT is approved in the US and Europe to treat castration-resistant prostate cancer and was also recently approved for men with metastatic hormone-sensitive prostate cancer (mHSPC) in the US. In ARCHES, enzalutamide plus ADT reduced the risk of the primary endpoint of radiographic progression-free survival events (by 61%), and improved key secondary endpoints versus placebo plus ADT in men with mHSPC.
Presented by Alicia Morgans, MD, MPH 
In a stand-alone session at this year’s Society of Urologic Oncology (SUO) virtual annual meeting, titled Understanding the Evolving Treatment Landscape in Prostate Cancer: How to Leverage the Latest Advances and Strategies to Optimize Patient Outcomes,
Presented by Ian Davis, MBBS, PhD, FRACP, FAChPM
The 2020 Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) Mini Annual Scientific Meeting featured a session on ANZUP trial updates, including an update of the critical Phase III ENZAMET trial provided by Drs. Ian Davis, Arun Azad, and Lisa Horvath.
Presented by Alicia Morgans, MD, MPH
In a session entitled “Sorting Through the Maze of Treatment Options for Metastatic Castration-Sensitive Prostate Cancer”, Dr. Alicia Morgans from Northwestern University presented a plenary talk discussing the treatment considerations for patients who received combination therapy for metastatic castration sensitive prostate cancer (mCSPC).
Presented by Neal D. Shore, MD, FACS
Dr. Shore from the Carolina Urologic Research Center presented a plenary talk discussing the multitude of hormonal treatment options for patients with metastatic castration sensitive prostate cancer (mCSPC). Dr. Shore began by highlighting data from Dr. Huggins seminal work demonstrating that prostate cancer is hormone dependent.
Presented by Neal D. Shore, MD, FACS
Treatment paradigms for patients with metastatic hormone-sensitive prostate cancer (mHSPC) have changed dramatically in the past 4 years. Before 2016, there were no agents with a demonstrated overall survival benefit in this disease space.
Presented by Alok Tewari, MD, PhD
San Francisco, California (UroToday.com) The second case in the challenging cases discussion was that of a 71-year-old man, a former smoker who suffers from hypertension,
Presented by Alicia Morgans, MD, MPH,
San Francisco, California (UroToday.com) As part of the Prostate Cancer Session at the 2020 American Society of Clinical Oncology Genitourinary Cancers Symposium
Presented by Christopher Sweeney, MBBS
Washington, DC (UroToday.com) Renowned medical oncologist Dr. Chris Sweeney provided an overview of the current landscape of metastatic castration sensitive prostate cancer
Presented by Markus Graefen, MD
Athens, Greece (UroToday.com) Markus Graefen, MD, gave an overview of the role of experimental metastases directed therapies in the era of proven life-prolonging drugs
Presented by Syed Adnan Ali, MBBS
Barcelona, Spain (UroToday.com) In the STAMPEDE study, low metastatic burden was determined to be predictive of overall survival (OS) benefit when radiation therapy (RT)
Presented by Martin R. Stockler, MBBS, MSc, FRACP
Barcelona, Spain (UroToday.com) ENZAmet is an international, cooperative group, randomized phase 3 trial. It recently showed that after a median follow-up of 34 months
Presented by Nicholas James, BSc, MB, BS, FRCP, FRCR, PhD
Barcelona, Spain (UroToday.com) Professor Nicholas James presented results from the STAMPEDE trial for the addition of docetaxel to first-line hormonal therapy for patients with
Presented by Andrew J. Armstrong, MD
San Francisco, CA (UroToday.com) Enzalutamide (ENZA) is an androgen receptor signaling inhibitor which inhibits the androgen receptor signaling pathway by blocking the binding of androgen to the androgen receptor as well as inhibition of nuclear translocation of the androgen receptor.1 Enzalutamide has been shown to be effective in improving overall survival in patients with metastatic castration resistant prostate cancer (mCRPC) both before and after chemotherapy.2,3
Presented by Paul L. Nguyen, MD
Barcelona, Spain (UroToday.com) Dr. Nguyen presented a summary of the latest news in the treatment of metastatic hormone-sensitive prostate cancer (mHSPC). Four recent major trials were summarized and discussed in this presentation.
Presented by Silke Gillessen, MD
Barcelona, Spain (UroToday.com) Dr. Silke Gillessen presented the medical oncologist’s perspective on the current and future treatment of prostate cancer. Her talk mainly focused on the role of systemic therapy in metastatic hormone-sensitive prostate cancer (HSPC).
Presented by Andrew J. Armstrong, MD
San Francisco, CA (UroToday.com) The introduction of androgen-axis targeted therapies has drastically altered the landscape of advanced prostate cancer. Abiraterone acetate (AA) and Enzalutamide (ENZA) have been driving the change, and have been utilized in even earlier stages of advanced prostate cancer.
Presented by Neil Rohit Parikh, MD, MBA
San Francisco, CA (UroToday.com) Dr. Parikh discussed that previously published data have suggested there may be a benefit for metastasis-directed therapy in patients with oligorecurrent hormone-sensitive prostate cancer. 
Presented by Celestia Higano, MD
Chicago, IL (UroToday.com) Celestia Higano, MD, gave an excellent talk on the topic of treatment toxicities in patients with metastatic hormone-sensitive prostate cancer (MHSPC). Dr. Higano began with the most important question in this topic, on how to decide which therapy to use in MHSPC. 
Presented by Neeraj Agarwal, MD
Chicago, IL (UroToday.com) Neeraj Agarwal provided a comprehensive overview of the treatment of mHSPC. Three general topics were reviewed – the current standard of care for men with (mHSPC), the role of definitive therapy of primary prostate cancer in the setting of mHSPC, 
Presented by Ulka Vaishampayan, MD
San Francisco, CA (UroToday.com) Dr. Vaishampayan and colleagues presented results of their randomized trial assessing enzalutamide vs bicalutamide in combination with androgen deprivation in metastatic hormone sensitive prostate cancer.