Welcome Letter from the Advanced Prostate Cancer Center of Excellence Editor

Zachary Klaassen | August 22, 2024

For more than 20 years, UroToday has been THE premier online educational resource for genitourinary oncology – clinicians educating clinicians. During this time, advanced prostate cancer has been completely transformed, pa≥ particularly in the last 10+ years. Since then, we have seen (briefly) the following in advanced prostate cancer:

  • Docetaxel for mCRPC progression
  • Cabazitaxel following docetaxel for mCRPC progression
  • Radium-223 for mCRPC
  • Docetaxel + ADT for mHSPC
  • Abiraterone + prednisone for mHSPC
  • ARPIs + ADT for mHSPC
  • ARPIs + ADT for M0 CRPC
  • Enzalutamide +/- ADT for non-metastatic HSPC
  • PARP inhibitors for mCRPC
  • Radioligand therapy for mCRPC

READ MORE PREVIOUS ARTICLES

Zachary Klaassen, MD, MSc

Zachary Klaassen, MD, MSc

Dr. Klaassen is a Urologic Oncologist, Associate Professor of Urology, Residency Program Director and the Ronald W. Lewis, MD Endowed Chair for Urologic Education at Wellstar MCG Health; Georgia Cancer Center in Augusta, GA. He was born in rural Canada and grew up in Vancouver, British Columbia. Following an undergraduate degree in Molecular Biology and Biochemistry at Simon Fraser University, he attended medical school at St. George's University in Grenada, followed by clinical rotations and a research fellowship in the metro New York area. After completing his Urology residency in Augusta, he spent two years in Toronto as a Society of Urologic Oncology fellow, obtaining a Masters of Science degree from the University of Toronto in Clinical Epidemiology. He specializes in Urology, Urologic Oncology, Robotic Surgery, Minimally Invasive Surgery, and Cancer Surgery. Dr. Klaassen is interested in treating patients with urologic malignancies, including prostate, bladder, kidney, testis, and penile cancer, using both open and minimally invasive surgical techniques. His research interests include mental health and cancer survivorship, clinical epidemiology of urologic malignancies, clinical trials, and translational research on biomarkers for early cancer detection and treatment response predictors. He believes in taking the cancer journey together with his patients and their families, focusing on treating not only the cancer but also the physical and emotional side effects of diagnosis and treatment.

Videos
Clinical Conversations by Experts
Physician-Scientist Review Articles
State of the Evidence Review Articles
Written by Zachary Klaassen, MD, MSc Associate Professor of Urology Urologic Oncologist Medical College of Georgia, Georgia Cancer Center Augusta, GA & Rashid Sayyid, MD, MSc Urologic Oncology Fellow University of Toronto Toronto, Ontario, Canada
April 4, 2024
Given the promising results that Poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors have demonstrated for the treatment of metastatic castrate-resistant prostate cancer (mCRPC) patients who had progressed following prior androgen receptor pathway inhibitor (ARPI) and/or taxane-based chemotherapy
Written by Zachary Klaassen, MD, MSc Associate Professor of Urology Urologic Oncologist Medical College of Georgia, Georgia Cancer Center Augusta, GA and Rashid Sayyid, MD, MSc Urologic Oncology Fellow University of Toronto Toronto, Ontario, Canada
March 27, 2024
Poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors are drugs that prevent the repair of DNA single-stranded breaks and promote their conversion to double-stranded breaks resulting in a synthetic lethality.1 These drugs have demonstrated promising results for the treatment
Written by Rashid K. Sayyid, MD, MSc Urologic Oncology Fellow University of Toronto Toronto, ON and Zachary Klaassen, MD, MSc Associate Professor Wellstar MCG Health Augusta, GA
March 15, 2024
Over the past decade, there have been significant advances in defining the genomic landscape of prostate cancer. The landmark study by Pritchard et al. published in The New England Journal of Medicine in 2016 demonstrated that germline DNA-repair gene mutations were present in approximately
Written by Rashid K. Sayyid, MD MSc University of Toronto Toronto, ON & Zachary Klaassen, MD MSc Georgia Cancer Center Wellstar MCG Health Augusta, Georgia
November 8, 2023
Since the United States Food and Drug Administration (FDA) approval of mitoxantrone in 19961 and docetaxel in 20042 for the treatment of patients with metastatic castrate-resistant prostate cancer, we have witnessed the approval of numerous additional agents/combinations in this disease space:
Written by Rashid Sayyid, MD MSc University of Toronto Toronto, ON & Zachary Klaassen, MD MSc Georgia Cancer Center Wellstar MCG Health Augusta, GA
November 8, 2023

Introduction

There have been significant advances in the metastatic castrate-resistant prostate cancer (mCRPC) treatment landscape with the emergence and approval of numerous agents in this disease space.
Written by Rashid K. Sayyid, MD MSc & Zachary Klaassen, MD MSc
May 24, 2023

Introduction: Despite the approval of numerous agents in this setting, patients with metastatic castrate-resistant prostate cancer (mCRPC) have a poor prognosis, with an estimated median overall survival (OS) of approximately three years with currently approved first-line agents.1-3

Written by Zachary Klaassen, MD, MSc and Rashid K. Sayyid, MD, MSc
April 14, 2023

Artificial intelligence continues to transform the field of medicine, including the management of prostate cancer. In this Center of Excellence article, we discuss the contemporary literature evaluating artificial intelligence for risk stratification after primary therapy, ADT treatment intensification, and evaluation of metastatic disease.

Written by Rashid Sayyid, MD MSc & Zachary Klaassen, MD MSc
January 5, 2023

While external beam radiotherapy is a standard treatment option as first-line therapy for men with localized prostate cancer, it has been more recently recognized as an important component in the care of men with metastatic prostate cancer. This Center of Excellence article will explore recent evidence for the utilization of radiotherapy in the metastatic setting.

Written by Rashid Sayyid, MD MSc, & Zachary Klaassen, MD MSc
October 19, 2022
While PSMA PET/CT is currently FDA approved for the initial staging of patients with presumed localized, high-risk prostate cancer and for the diagnostic work up of patients with biochemical failure following primary treatment, the role of PSMA PET/CT in patients with known metastatic prostate cancer is not as well-defined.
Written by Rashid Sayyid, MD, MSc, & Zachary Klaassen, MD, MSc
September 7, 2022
While there have been clear survival benefits for patients with metastatic castration resistant prostate cancer (mCRPC) with the use of taxane chemotherapy and novel androgen receptor targeting agents, most patients eventually progress following these treatments.
Written by Rashid Sayyid, MD MSc, & Zachary Klaassen, MD MSc
September 7, 2022
Radiopharmaceuticals are pharmaceutical agents which contain radioisotopes that emit radiation, which may be used for diagnostic or treatment purposes. Historically, beta-particle emitting agents including strontium-89 (Metastron), samarium-153 (Quadramet), phosphorus-32, and rhenium-186 were used as palliative therapies for patients with symptomatic bone disease.
Written by Rashid Sayyid, MD MSc, & Zachary Klaassen, MD MSc
September 6, 2022

While the emergence of castration resistant disease comes as a result of the disease progressing in spite of castrate levels of testosterone (at times called hormone refractory disease), prostate cancer (even in the castration resistance prostate cancer (CRPC) setting) remains heavily dependent on the androgen axis.

Written by Zachary Klaassen, MD MSc and Rashid Sayyid, MD MSc
August 30, 2022

Prostate cancer, while commonly diagnosed as localized disease, remains the second leading cause of cancer mortality in the United States and Europe.1 For patients who die of prostate cancer, some will be initially diagnosed and treated for metastatic hormone-sensitive disease (mHSPC).

Written by Zachary Klaassen, MD, MSc
July 2, 2020
Prostate cancer is a clinically heterogeneous disease with many patients having an indolent course requiring no interventions and others who either present with or progress to metastasis. While underlying dominant driving mutations are not widespread, there have been a number of key genomic mutations that have been consistently identified in prostate cancer patients,
Written by Zachary Klaassen, MD, MSc
May 14, 2020
The coronavirus has the potential to impact the integrity and patient safety of ongoing trials as well as increase the operational burden on trial programs, therefore potentially limiting access to trials and new therapies for oncology patients. Opportunities for clinical trial enrollment may still be provided to patients during the COVID-19 outbreak, but likely require thorough evaluation on a case-by-case basis.
Written by Zachary Klaassen, MD, MSc
December 10, 2019

Despite prostate cancer (PCa) being the second most common cause of cancer mortality among American men,1 there are 2.9 million men in the United States living with PCa. As such, there are many “PCa survivors” that are either on active surveillance (AS)/watchful waiting (WW) or have undergone treatment for localized (ie. radiation therapy (RT), radical prostatectomy (RP), focal therapy, etc) or advanced disease. 

Written by Zachary Klaassen, MD, MSc
December 18, 2019

Understanding and elucidating the underlying genetic basis of carcinogenesis has been the holy grail for cancer researchers, for both the scientific understanding of disease pathophysiology and potential therapeutic implications. Perhaps the best example of the therapeutic implications of understanding carcinogenesis come from chronic myeloid leukemia where the identification of the “Philadelphia chromosome”;

Written by Zachary Klaassen, MD, MSc
November 15, 2019
Despite the exciting advances in treatment over the last decade for metastatic castration-resistant prostate cancer (mCRPC), the disease remains incurable with a median overall survival of 12-35 months.1-4 Targeting the immune system to expand treatment options in the advanced disease state has resulted in significant improvements
Written by Hanan Goldberg, MD
December 10, 2019
In 2018 1.3 million prostate cancer (PCa) cases were diagnosed worldwide, with approximately 20% having metastatic disease.1 Oligometastatic PCa is defined as a state of low-volume metastatic disease that appears to be prognostically different and likely amenable to different treatment options, which could potentially change the disease trajectory when compared with high-volume metastatic disease.2
Written by Zachary Klaassen, MD, MSc
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).1 Over the last four decades, there was a spike
Written by Zachary Klaassen, MD, MSc
April 16, 2019
The discovery of prostate-specific antigen (PSA) in the late 1970s and its widespread application and adoption in the 1980s and 1990s ushered in the prostate cancer screening and disease monitoring era. As the first tumor marker for prostate cancer, it is organ specific but not cancer specific.1
Physician-Scientist Commentaries
Peer-reviewed Abstract Supplemental Commentaries
Written by Christopher Wallis, MD, PhD, FRCSC, Assistant Professor, Division of Urology, University of Toronto
Beginning with the data from TAX-327 demonstrating the overall survival advantage of docetaxel in men with metastatic castration-resistant prostate cancer (mCRPC), this disease space has gone from one of the repeated dead-ends to a flourishing research field with many agents gaining approval over the last 15 years as a result of demonstrated survival benefits.
Conference Coverage
Conference Highlights Written by Physician-Scientist
Presented by Ruth E. Langley, PhD
The 2024 ESMO annual meeting included a session on prostate cancer, featuring a presentation by Dr. Ruth Langley discussing efficacy results from a randomized phase 3 evaluation of transdermal estradiol versus luteinizing hormone-releasing hormone (LHRH) agonists for androgen suppression in M0 prostate cancer.
Presented by Irene Burger, MD
The 2024 European Society for Medical Oncology (ESMO) Annual Congress held in Barcelona, Spain between September 13th and 16th, 2024 was host to a proffered paper session for prostate cancer. Professor Irene Burger provided the discussant for both SPLASH and UpFrontPSMA.
Presented by Elena Castro, MD, PhD
The 2024 European Society of Medical Oncology (ESMO) Annual Congress held in Barcelona, Spain was host to the session Therapeutic options beyond AR pathway inhibitors: What do we choose next? Dr. Elena Castro discussed if cytotoxics are still the next option after ARPIs.
Presented by Karim Fizazi, MD, PhD
The 2024 ASCO featured a session on prostate cancer, and a presentation by Dr. Karim Fizazi discussing results from PSMAfore, specifically health-related quality of life and pain among taxane-naïve metastatic castration-resistant prostate cancer (mCRPC) patients treated with 177Lu-PSMA-617. 
Presented by  Christos Kyriakopoulos, MD
The 2024 ASCO annual meeting featured an oral abstract session on prostate cancer, and a presentation by Dr. Christos Kyriakopoulos discussing results of the CHAARTED2 trial assessing cabazitaxel with abiraterone versus abiraterone alone for extensive disease following docetaxel.
Presented by Matthew R. Smith, MD, PhD
The 2024 American Society of Clinical Oncology (ASCO) annual meeting featured a session on prostate cancer, and a presentation by Dr. Matthew Smith discussing results of CYCLONE 2, a phase 3 trial assessing abemaciclib with abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC). Oncogenic addiction to androgen receptor signaling drives mCRPC progression, highlighting the unmet need for novel treatment strategies to maximize androgen receptor-directed therapy.
Presented by Geoffrey Johnson, MD, PhD
During the 2024 ASCO GU cancers symposium, Dr. Geoffrey Johnson presented the study framework of SECuRE, a dose escalation/expansion study to assess the anti-tumor efficacy of 67Cu-SAR-bisPSMA in patients with metastatic castrate-resistant prostate cancer (mCRPC).
Presented by Maha Hussain, MD
Maha Hussain discussing BRCAAway, a randomized phase 2 trial of abiraterone, olaparib, or abiraterone + olaparib in patients with metastatic castration-resistant prostate cancer (mCRPC) bearing homologous recombination-repair (HRR) mutations.  
Presented by Neeraj Agarwal, MD
Neeraj Agarwal presented CONTACT-2, a phase 3 study of cabozantinib + atezolizumab vs second novel hormonal therapy in patients with metastatic castration-resistant prostate cancer (mCRPC).
Presented by Karim Fizazi, MD, PhD
Dr. Karim Fizazi presented the results of CYPIDES, a phase 2 trial evaluating MK-5684 (ODM-208), a CYP11A1 inhibitor, in patients with metastatic castration-resistant prostate cancer (mCRPC) with and without androgen receptor (AR) ligand binding domain (LBD) mutations.
Presented by Oliver Sartor, MD
Oliver Sartor presented the safety outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223 following external beam radiation therapy in the REASSURE study.
Presented by Daniel Y. Song, MD
The 2023 ASCO annual meeting included a prostate cancer session, featuring a presentation by Dr. Daniel Song discussing the REASSURE study assessing real-world safety and effectiveness of Radium-223 in patients with metastatic castration-resistant prostate cancer (mCRPC) treated in the US. Radium-223 improved overall survival and quality of life and demonstrated a favorable safety profile in patients with mCRPC in the phase 3 ALSYMPCA trial.
Presented by Joaquin Mateo, MD, PhD
At the 2023 ASCO annual meeting Dr. Mateo discussed two abstracts including “PANTHER: A prospective trial of apalutamide and abiraterone acetate plus prednisone in Black and White men with mCRPC” presented by Dr. Daniel George, and “STARTAR: A phase 2 salvage trial of androgen receptor inhibition with ADT and apalutamide with radiation therapy followed by docetaxel in men with PSA recurrent prostate cancer after radical prostatectomy” presented by Dr. Tian Zhang.
Presented by Ravi Amrit Madan, MD
In the discussant presentation at the 2023 ASCO annual meeting Dr. Ravi Madan discussed quality in the context of quantity: evaluating treatment intensification. He discussed three abstracts presented in this session:
Presented by Neeraj Agarwal, MD, FASCO
TALAPRO-2 is a phase III study evaluating the combination of the poly (ADP-ribose) polymerase inhibitor talazoparib and enzalutamide versus enzalutamide and placebo as first-line treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). It exists in the landscape of sequential and advancing studies of PARP inhibitors (PARPi) in prostate cancer.
Presented by Ana Aparicio, MD
The second Prostate Cancer Session of the Annual Meeting of the Society of Urologic Oncology was held on Friday, December 2nd, 2022. In this session, Dr. Ana Aparicio presented on the role of biomarkers and somatic testing to guide treatment choice in advanced prostate cancer.
Presented by Samuel L. Washington III, MD, MAS
The 23rd Annual Meeting of the SUO was host to a prostate cancer session. Dr. Samuel L. Washington III, MD, MAS presented the results of a population-based analysis evaluating geographic variations in the utilization of doublet therapy for metastatic prostate cancer patients.
Presented by Fred Saad, MD, FRCS
The 2022 ESMO annual meeting featured a prostate cancer session, including a presentation by Dr. Fred Saad discussing a biomarker analysis and updated results from the Phase III PROpel trial of abiraterone and olaparib vs abiraterone and placebo as first-line therapy for patients with mCRPC.
Presented by Michael S. Cookson, MD, MMHC
In a podium presentation in the Prostate cancer IV - Advanced disease session at the 19th Meeting of the EAU Section of Oncological Urology, Dr. Cookson presented on the changing face of prostate cancer, with important implications for our practice of evidence-based medicine.
Presented by William Thomas Lowrance, MD, MPH, MBA
In this plenary session, Dr. William Thomas Lowrance summarized the 2021 AUA/ASTRO/SUO guidelines on advanced prostate cancer, with key take-home points highlighted. The full 2 part guidelines1,2 can be found online at They are also published in the Journal of Urology.
Presented by Stephen A. Boorjian, MD
The Society of Urologic Oncology held an associated session at the American Urologic Association Virtual Annual Meeting entitled “The Evolving Landscape of Advanced Prostate Cancer Treatment: A Guidelines and Case-Based Discussion.” Dr. Stephen Boorjian began this session with a talk focusing on the identification of patients with high-risk prostate cancer and the initial management of those with biochemical recurrence following therapy.
Presented by Michael Cookson, MD, MMHC
As the therapeutic landscape evolves to include increasingly complex combinations of systemic therapies with or without local therapies, advances in imaging, and germline and somatic testing, treating men with advanced prostate cancer is increasingly one that must embrace multidisciplinary management approaches.
Presented by Neal D. Shore, MD, FACS, and Ashley Evan Ross MD, PhD
During the second prostate cancer session at the 2020 Annual Meeting of the Society of Urologic Oncology (SUO), Drs. Neal Shore and Ashley Evan Ross debated the use of relugolix as a new standard of care for androgen deprivation therapy (ADT) for the treatment of prostate cancer.
Presented by Reham Alghandour, PhD
Metformin is a biguanide agent which is commonly used in the first-line treatment of patients with type 2 diabetes. For many years, there has been an interest in its potential anti-cancer properties, particularly in prostate cancer.
Presented by William T. Lowrance, MD, MPH
The AUA 2020 virtual annual meeting was highlighted by an update on the AUA guidelines for advanced prostate cancer, presented by Dr. William Lowrance and Dr. Michael Cookson. Dr. Lowrance notes that this guideline was produced by a multidisciplinary panel with representation from the AUA, ASCO, ASTRO, and SUO was well as a patient advocate.
Presented by Elena Castro, MD, PhD
San Francisco, CA (UroToday.com) In this talk, Dr. Elena Castro gave an overview of the genomic landscape of advanced prostate cancer. It has been shown that in over 70%
Presented by Samuel Denmeade
Washington, DC (UroToday.com) As part of the SUO 2019 advanced prostate cancer session, Dr. Samuel Denmeade discussed his work with bipolar androgen therapy (BAT)
Presented by Samuel Denmeade, MD
Washington, DC (UroToday.com)  Since Huggins’ noble prize-winning work on the role of androgens in prostate cancer progression in 1940, hormonal suppression has been the mainstay
Presented by Kelly Stratton, MD
Athens, Greece (UroToday.com) Dr. Kelly Stratton gave an overview of the role of surgery in advanced prostate cancer. Advanced prostate cancer 
Presented by Derya Tilki, MD
Athens, Greece (UroToday.com) Dr. Derya Tilki was the first to present at the Educating Masterclass on Biochemical Recurrence after Radical Prostatectomy.
Presented by Karim Fizazi, MD, PhD
Barcelona, Spain (UroToday.com) At the Friday session at the 2019 European Society for Medical Oncology annual meeting (ESMO) meeting on prostate cancer, Karim Fizazi
Presented by Maria J. Ribal, MD
Barcelona, Spain (UroToday.com) Dr. Maria Ribal from Barcelona started the urogenital cancer treatment at a glance session by giving an overview of challenging paradigms in advanced prostate cancer. Dr. Ribal notes that not only is the incidence of prostate cancer the highest among male malignancies,
Presented by Himisha Beltran, MD
San Francisco, CA (UroToday.com) Dr. Misha Beltran presented a summary of the biologic basis for sequencing novel treatments for metastatic prostate cancer.  There is an increasing need for biomarkers in advanced prostate cancer management
Presented by Srikala S. Sridhar, MD, FRCPC, Alberto Briganti, MD, PhD, and Heather Ann Payne, MBBS, FRCP, FRCR
San Francisco, CA (UroToday.com) During the general session on optimizing diagnosis and treatment of clinically significant nonmetastatic prostate cancer at the Annual ASCO GU 2019 meeting
Presented by Kim Chi, MD
Phoenix, Arizona (UroToday.com) The LATITUDE study, published in July 2017, was a phase III randomized, clinical trial that evaluated the efficacy of abiraterone 
Presented by Laurence Klotz, MD
Tel-Aviv, Israel (UroToday.com) Laurence Klotz, MD gave a presentation on intermittent androgen deprivation therapy (IADT) and its association with cardiovascular disease (CVD). He began stating the many advantages of intermittent androgen deprivation therapy.
Presented by Jehonathan Pinthus, MD
Tel-Aviv, Israel (UroToday.com) Jehonathan Pinthus, MD presented the RADICAL PC trial and elaborated on the correlation of prostate cancer (PC) to cardiovascular disease (CVD). It is known that PC patients are at risk for CVD. Patients are deemed to be high-risk if they have a global risk estimate for severe CVD events with a rate of more than 2% per year.
Presented by Silke Gillessen, MD
Copenhagen, Denmark (UroToday.com)  Dr. Sommer gave an overview of the complications associated with the treatment for advanced prostate cancer. The first topic discussed was the acute side effects of androgen deprivation therapy (ADT). These include decreased libido, erectile dysfunction, hot flashes, and fatigue.
Presented by Karim Fizazi, MD, PhD
Chicago, IL (UroToday.com) Dr. Karim Fizazi and colleagues presented their much-anticipated results from the LATITUDE trial at the 2017 ASCO annual meeting’s plenary session. In a phase III, double-blind, randomized setting, LATITUDE tested androgen deprivation therapy