Radium-223 in 2024 and Beyond: Resurrected and Disrupting the First-Line mCRPC Treatment Landscape
Written by Rashid Sayyid MD, MSc and Zachary Klaassen, MD, MSc
October 30, 2024
Introduction
Radium-223 dichloride (radium-223) is a targeted alpha emitter that selectively binds to areas of increased bone turnover in bone metastases and emits high-energy alpha particles of short-range (<100 μm). Radium-223 acts as a bone-seeking calcium mimetic and binds into newly formed bone stroma, especially within the microenvironment of osteoblastic or sclerotic metastases. Double-stranded DNA breaks result secondary to the high-energy alpha-particle radiation.
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Radioligand Therapy for Metastatic Castrate-Resistant Prostate Cancer: Radium-223, 177Lu-PSMA-617, New Agents, and Novel Combinations
Written by Rashid K. Sayyid, MD, MSc, University of Southern California, Los Angeles, CA and Zachary Klaassen, MD, MSc, Wellstar MCG Health, Augusta, GA
August 23, 2024
Introduction
The treatment landscape of metastatic castrate-resistant prostate cancer (mCRPC) has long been dominated by androgen receptor pathway inhibitors (ARPIs) and chemotherapeutic agents. There are currently, however, two radioligands that are United States Food and Drug Administration (FDA)-approved for the treatment of mCRPC patients:
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PARP Inhibitor Therapy for Prostate Cancer Patients: Emerging Combinations
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
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PARP Inhibitor Monotherapy for Prostate Cancer Patients
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
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Novel Treatment Targets in the Metastatic Castrate-Resistant Prostate Cancer Disease Space
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 1996
1 and docetaxel in 2004
2 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:
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The Current State of Treatment Implementation for mCRPC in North America
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.
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PARP Inhibitor Plus Androgen Receptor Signaling Inhibitor Combinations: Will This Be The Future of mCRPC First-Line Therapy?
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
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The Current Landscape of PSMA PET Imaging in Prostate Cancer: Advanced Prostate Cancer
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.
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The Current Landscape of Metastatic Castration-Resistant Prostate Cancer: Immunotherapy and Targeted Therapies
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.
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The Current Landscape of Metastatic Castration-Resistant Prostate Cancer: Radioligand Therapy
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.
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Ethnic Variation in Prostate Cancer Detection: A Feasibility Study for Use of the Stockholm3 Test in a Multiethnic U.S. Cohort - Beyond the Abstract
Written by Hari T. Vigneswaran, Andrea Discacciati, Peter H. Gann, Henrik Grönberg, Martin Eklund, Michael R. Abern
August 17, 2020
African American men are known to have nearly twice the incidence of prostate cancer and more than double the risk of prostate cancer mortality compared to Caucasian men. There are several possible mechanisms for this including risk factors such as lifestyle, diet, genetic risk, inequalities in access to high-quality care, or other socioeconomic factors, however, the contribution of biology in prostate cancer risk is not well understood in this population.
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PARP Inhibitors, Prostate Cancer and a Promise Fulfilled
Written by Charles Ryan, MD
June 30, 2020
June 26, 2020, marked the 20
th anniversary of the publication of the first working draft from the Human Genome Project. At a special White House event to commemorate the results of this 10-year public effort (it was really more like 50 years since the discovery of DNA, but I digress), then-President Bill Clinton called the project “the most wondrous map ever created by humankind”, and touted its promise to detect, prevent, and treat disease.
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PARP Inhibitors - A Breakthrough in Targeted Therapies for Prostate Cancer
Written by Arpit Rao, MBBS and Charles Ryan, MD
June 29, 2020
In this review, we will summarize the current indications for PARP inhibitor monotherapies and combination(s), review data from clinical trials in prostate cancer, discuss management of commonly encountered side effects, and highlight exciting clinical research on expanding the role of PARP inhibitors in prostate cancer.
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Germline Testing for DNA Repair Mutations in Prostate Cancer: Who, When and How?
Written by Veda N. Giri, MD
June 29, 2020
Understanding the role of germline testing in prostate cancer is now critical to urologic and oncology practice for metastatic castration-resistant prostate cancer. Here, we will address who should be considered for germline testing, when germline testing may influence treatment and management, and
how to implement germline testing involving provider practices and genetic counseling.
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What Are the Most Common Genomic Aberrations Seen in DNA Damage Response (DDR) Pathways in Advanced Prostate Cancer?
Written by Patrick G. Pilié, MD
June 29, 2020
Men with advanced prostate cancer have a 10-15% risk of carrying a hereditary, or germline, variant in a DNA damage response gene. Pathogenic or deleterious variants in these same DNA damage response genes can also be found at the somatic, or tumor-associated level, in up to 25% of metastatic castrate-resistant prostate cancer.
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PARP Inhibitors in Prostate Cancer: PROfound and Beyond
Written by Zachary Klaassen, MD, MSc
June 17, 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, across the disease spectrum
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A Contemporary Update on Sipuleucel-T for Men with Metastatic Castrate-Resistant Prostate Cancer
Written by Christopher J.D. Wallis, MD, PhD and Zachary Klaassen, MD, MSc
April 21, 2020
There are a growing number of treatment options for patients with metastatic castrate-resistant prostate cancer including those targeting the androgen axis (abiraterone acetate plus prednisone and enzalutamide), cytotoxic chemotherapy (docetaxel and cabazitaxel), radiopharmaceuticals (radium-223), and immunotherapeutic approaches (sipuleucel-T).
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Contemporary Radiotherapy Clinical Trials for Prostate Cancer
Written by Zachary Klaassen, MD, MSc
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 with conventionally fractionated radiotherapy among patients with intermediate-risk to high-risk T1b-T4NX-N0MX-M0 localized prostate cancer.1
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Bone-Targeted Therapy in Prostate Cancer
Written by Zachary Klaassen, MD, MSc
December 10, 2019
Prostate cancer metastases to the bone is a late manifestation of the prostate cancer disease spectrum, often painful for the patient and potentially dangerous in the setting of skeletal-related events. Among prostate cancer patients, the cumulative incidence of bone metastasis at one and five years after diagnosis is 8% and 17%, respectively
1.
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Beyond First-line Treatment of Metastatic Castrate-resistant Prostate Cancer
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.
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First-line Treatment for Metastatic Castrate-resistant Prostate Cancer
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.
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Expanding Treatment Options in Non-metastatic Castrate-resistant Prostate Cancer
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 Read More
The Impact of Visceral Metastasis in Prostate Cancer Patients
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).
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