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The Latest Research on CRPC with Bone Metastases

Curated by clinicians: educational forums with videos, abstracts and conference information
Rana R. McKay, MD

Rana R. McKay, MD is an Associate Professor of Medicine and Urology at the University of California San Diego and Co-Leader of the Genitourinary Oncology Disease Team at the Moores Cancer Center. She is a board-certified medical oncologist who specializes in treating people with urogenital cancers, including bladder, kidney, prostate, and testicular cancer. Her research interests include the design and implementation of clinical trials to advance the treatment of patients with urologic cancers. She serves as the Principal Investigator of several early phase trials in kidney and prostate cancer. As a clinical investigator, she is committed to advancements that will improve the lives of individuals with cancer. Furthermore, she is interested in understanding mechanisms of response and resistance to specific cancer therapies. Her work has appeared in peer-reviewed publications such as the Nature, Lancet, Journal of Clinical Oncology, Clinical Cancer Research, Cancer, among others. Dr. McKay earned her medical degree at the University of Florida College of Medicine before completing her residency in Internal Medicine at Johns Hopkins Hospital. She completed a fellowship in Oncology/Hematology at the Dana-Farber Cancer Institute, Harvard Medical School. She went on to serve as an Assistant Professor at Harvard Medical School and a medical oncologist at Dana-Farber/Brigham and Women's Cancer Center in Boston before joining UC San Diego Health.

Videos
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Clinical Conversations by Experts
Bone-Protective Agents and Survival Benefits in PEACE-3 Trial Subgroup Analysis - Fred Saad
Real-World Trends in Bone Health Agent Use for Metastatic Prostate Cancer - Umang Swami
REDUSE Trial: Comparing Denosumab Dosing Intervals in mCRPC - Arnoud Templeton
PEACE 3 Trial Results Show Promise for Radium-223 and Enzalutamide in Asymptomatic mCRPC - Fred Saad
2024 NCCN Guidelines: Managing Bone Health in Prostate Cancer Patients - Rashid Sayyid & Zachary Klaassen
Alpha vs Beta Emitters in Prostate Cancer Radiopharmaceuticals: Energy, Range, and Cytotoxicity - Alan Bryce
Safety and Disease Related Outcomes of mCRPC Patients Who Were Treated with Radium-223 Then 177Lu-PSMA (RALU) - Neal Shore
The Association Between the Time Interval Between Sequential Treatment With Radium-223 Therapy and 177Lu-PSMA in the RALU Study - Kambiz Rahbar
Sequencing Radiopharmaceuticals: Efficacy and Safety Data of Radium-223 Followed by Lutetium-177-PSMA in the RALU Study - Oliver Sartor
Optimal Treatment Sequencing with Radiopharmaceuticals After Radium-223 in Men with Newly Progressed Prostate Cancer – A Cased Based Review - Phillip Koo, Neal Shore, & Alicia Morgans
Optimizing Multi-Disciplinary Care Teams for Radiopharmaceutical Administration - Neal Shore
The Correlation Between Alkaline Phosphatase Decline and Overall Survival in Men with Metastatic Castration-Resistant Prostate Cancer in the REASSURE Study - Nicholas James
223Ra Use Before 177Lu-PSMA for Patients with Bone-predominant mCRPC, The RAdium LUtetium (RALU) Study, Journal Club - Zachary Klaassen
Multidisciplinary Care Teams to Optimize Care of Patients with Bone Metastatic CRPC - Tanya Dorff
Optimizing the Use of Radium-223 Through Multidisciplinary Collaboration - Phillip Koo
Treatment Sequencing with Radium-223 in Symptomatic Disease - Fred Saad
A Real-World Analysis of Pain Efficacy of Radium-223 Treatment Among Patients With Metastatic Castration-Resistant Prostate Cancer and Symptomatic Bone Metastases – the REASSURE Trial – Celestia Higano
Real-World Safety and Effectiveness of Radium-223 in Japanese Patients with Castration-Resistant Prostate Cancer (CRPC) and Bone Metastasis - Beyond the Abstract
The NCCN Guidelines on the Use of Radium-223 in Prostate Cancer - Tanya Dorff
Optimal Patient Selection for Treatment with Radium-223 in mCRPC Towards Improved Overall Survival and Improved Quality of Life - Brenda Martone
Ensuring Patients Have Access to Radium-223 as a Therapeutic Option: The DORA Trial - Michael Morris
The Effect of Mandated Bone Protective Agents on Fracture Risk With Longer Follow-Up (EORTC 1333 / PEACE III Trial) – Fred Saad
Radium-223 plus Enzalutamide vs Enzalutamide Alone in Metastatic Castration-Resistant Prostate Cancer - Benjamin Maughan
The Combination of Pembrolizumab and Radium-223 in Metastatic Castration-Resistant Prostate Cancer (mCRPC) - Atish Choudhury
Sequential Radium-223 Treatment of mCRPC That Progressed After First-Line Novel Antihormonal Therapy, A Real-World Clinical Outcomes Study - Oliver Sartor
Bone Health and Osteoclast Targeted Therapies in Advanced Prostate Cancer - Matthew Smith
Bone Targeted Theranostics with 18F-NaF/ 223Ra Cl2 in Prostate Cancer - Hossein Jadvar
Real-World Clinical Outcomes with Radium-223 in Metastatic Castration-resistant Prostate Cancer - Neal Shore
Radium 223 Dichloride Use in Patients with Castrate Resistant Prostate Cancer - Hossein Jadvar
The Risk of Dose De-intensifying Treatment, Bone Health in Prostate Cancer - Fred Saad
Radium-223 and Bone Health Agents: Lessons Learned Presentation - Oliver Sartor
Antiresorptive Therapy to Reduce SRE Risk For The Majority of Men with CRPC and Bone Metastases Presentation - Bertrand Tombal
Radium-223 in Clinical Practice - Phillip J. Koo
Decreased Fracture Rate When Adding Bone Protecting Agents to Radium-223: PEACE III- Bertrand F. Tombal
Real World Treatment Experience with Radium-223 - Dan George
Bone Health in Prostate Cancer - A Conversation with Neal Shore and Oliver Sartor
Physician-Scientist Review Articles
State of the Evidence Review Articles
January 30, 2025
Bone metastases are at the center of advanced prostate cancer care, with over 90% of patients with metastatic prostate cancer expected to have bone involvement.1 These metastatic sites can be a cause of substantial pain in our patients, and they have been a key target for therapeutic development. Bone targeted agents have been developed to reduce fragility fractures and skeletal related events, and are now an integral part of the care of patients with metastatic prostate cancer,2,3 Further, radium-223 is a bone-targeted radiopharmaceutical that not only reduces pain burden but was also the first radiopharmaceutical to prolong survival in patients with prostate cancer. Over time prostate cancer studies have investigated the prognostic implications of bone metastases in comparison with other sites and helped us gain insight into the potential future progression or responsiveness of disease.4 Bone metastases have played a large role in the clinical care of patients with prostate cancer, and our approach to them continues to evolve.
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.
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:

Written by Zachary Klaassen, MD, MSc
February 27, 2020

Patients with advanced prostate cancer are at significant risk of skeletal-related events (SREs) due to a complex interplay between bone health and prostate cancer due to cancer biology and the predilection of prostate cancer to spread to bone, the toxicity of prostate cancer treatments, and shared epidemiology of the two conditions.

 

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%, respectively1.
Written by Christopher J.D. Wallis, MD, PhD and Zachary Klaassen, MD, MSc
December 3, 2019
Radiopharmaceuticals are pharmaceutical agents containing radioisotopes and emitting radiation that may be used for diagnostic or treatment purposes. The ALSYMPCA trial was the first to demonstrate that radiopharmaceuticals could improve overall survival, in addition to skeletal-related events, in patients with metastatic castrate-resistant prostate cancer. On the basis of this observation, there is an ongoing effort to identify molecular targets for linkage to radiopharmaceuticals.
Written by Zachary Klaassen, MD, MSc
April 16, 2019
Prostate cancer exhibits a wide spectrum of disease behaviour. Despite the majority of cases presenting with relatively indolent biologic behaviour, prostate cancer remains the second leading cause of cancer-related death in the United States, behind only lung cancer.
Conference Coverage
Conference Highlights Written by Physician-Scientist
Presented by Fred Saad, MD, FRCS
The 2025 EAU annual meeting featured a prostate cancer session and a presentation by Dr. Fred Saad discussing a subgroup analysis of the PEACE 3 phase III trial assessing the impact of bone protecting agents on the efficacy and safety of enzalutamide versus combination of radium-223 and enzalutamide in asymptomatic or mildly symptomatic patients with bone metastatic castration-resistant prostate cancer (mCRPC). PEACE-3 was an international study in 446 patients with mCRPC and bone metastases randomized 1:1 to combination of enzalutamide and radium-223 versus enzalutamide alone:
Presented by Karim Fizazi, MD, PhD & Bertrand Tombal, MD, PhD
The 2025 European Association of Urology (EAU) Annual Congress held in Madrid, Spain between March 21st and 24th 2025, was host to an ‘Advanced Prostate Cancer Consensus Conference (APCCC) Meets EAU’ thematic session. Drs. Karim Fizazi and Bertrand Tombal discussed the pros and cons of de-escalation of systemic therapy in metastatic hormone-sensitive prostate cancer (mHSPC) patients with a deep response to androgen deprivation therapy (ADT) plus an androgen receptor pathway inhibitor (ARPI).
Presented by Rana R. McKay, MD
The 2025 GU ASCO annual meeting featured a prostate cancer session and a presentation by Dr. Rana McKay discussing a systematic review assessing the effectiveness of radium-223 in men with metastatic castration-resistant prostate cancer (mCRPC). Radium-223 has been approved for men with mCRPC with bone metastases since 2013 based on the phase 3 ALSYMPCA trial.
Presented by Ana Kiess, MD, PhD
The 2024 ASTRO annual meeting included a late-breaking abstract session, featuring a presentation by Dr. Ana Kiess discussing outcomes of the RAVENS phase 2 randomized trial assessing outcomes of radium-223 + stereotactic ablative radiotherapy versus stereotactic ablative radiotherapy alone for oligometastatic prostate cancer. Previously, the STOMP1 and ORIOLE2 randomized clinical trials showed progression-free survival benefits of metastasis-directed therapy alone without ADT for oligometastatic hormone-sensitive prostate cancer:
Presented by Deborah Mukherji, MBBS, FRCP
 The 2024 ESMO annual meeting included a session on prostate cancer, featuring a discussant presentation by Dr. Deborah Mukherji discussing two abstracts including “RAPSON: Open-label, multicenter randomized trial of Radium-223 -> docetaxel versus docetaxel -> Radium-223 sequence in mCRPC with prospective biomarker evaluation” by Dr. Vincenza Conteduca and “Adding metformin to ADT for patients with mHSPC: Overall survival results from the multi-arm, multi-stage randomized platform trial STAMPEDE” by Dr. Silke Gillessen.
Presented by Vincenza Conteduca, MD
The 2024 ESMO annual meeting included a session on prostate cancer, featuring a presentation by Dr. Vincenza Conteduca discussing results from RAPSON, an open-label multicenter randomized trial of Radium-223 -> docetaxel versus docetaxel -> Radium-223 sequence in mCRPC with prospective biomarker evaluation. Defining the most effective treatment sequence between the α emitter Radium-223 and docetaxel is pivotal for optimizing bone-dominant mCRPC outcomes.
Presented by Silke Gillessen Sommer, MD
(UroToday.com) The 2024 European Society for Medical Oncology (ESMO) Annual Congress held in Barcelona, Spain between September 13th and 16th, 2024 was host to a presidential symposium of practice-changing trials. Professor Silke Gillessen presented the initial results of EORTC-GUCG 1333/PEACE-3
Presented by Kambiz Rahbar, MD
The 2024 ESMO annual meeting included a session on prostate cancer, featuring a presentation by Dr. Kambiz Rahbar discussing the final safety and efficacy analysis of RaLu assessing 177Lu-PSMA therapy in patients with prior radium‑223. Radium-223 is an established alpha particle emitting radionuclide therapy with an acceptable safety profile.
Presented by Meryam Losee, BS
At the SNMMI 2024 Annual Meeting, Dr. Meryam Losee presented the results of a study evaluating the effect of bone marrow disease on hematologic toxicity and PSA response to 177Lu-PSMA-617 therapy. 
Presented by Ashwin Sachdeva, MBBS, PhD, FRCS
The 2024 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago, IL between May 31st and June 4th, 2024 was host to a session addressing techniques to minimize the effects of androgen deprivation therapy (ADT) while explore alternatives in prostate cancer management. Dr. Ashwin Sachdeva discussed the appropriate use and timing of bone resorptive agents in patients with advanced prostate cancer.
Presented by Amit D. Raval, PhD
The 2024 GU ASCO annual meeting featured a prostate cancer session and a presentation by Dr. Amit Raval discussing real-world utilization patterns of radium-223 in metastatic prostate cancer in the United States. Radium-223 is approved for use in men with symptomatic castration-resistant prostate cancer (CRPC) with bone metastases, demonstrating benefits in terms of overall survival and quality of life with a reliable safety profile.1
Presented by Hanbo Zhang, MD, FRCPC
The 2024 GU ASCO annual meeting featured a prostate cancer session and a presentation by Dr. Hanbo Zhang discussing a real-world analysis of survival and fracture risk with radium-223 therapy in metastatic castrate-resistant prostate cancer (mCRPC). Radium-223 is a life-prolonging radionuclide therapy for men with bone-predominant mCRPC based on the phase 3 ALSYMPCA trial.
Presented by Joe O'Sullivan, MD FRCPI, FFRRSCI, FRCR
The 2022 ESMO annual meeting featured a prostate cancer session, including a presentation by Dr. Joe O'Sullivan discussing alkaline phosphatase decline and pain response as markers for overall survival in patients with mCRPC treated with radium-223 in the REASSURE study.
Presented by Elena Castro, MD
In the on-demand poster session of the ESMO Annual Congress, Dr. Elena Castro presented results from the PRORADIUM cohort (NCT02925702) examining the effect of germline mutations on outcomes for patients treated with radium-223.
Presented by Celestia S. Higano, MD, FACP
In the on-demand poster session of the ESMO Annual Congress, Dr. Higano presented a real-world analysis of pain efficacy of radium-223 treatment among patients with metastatic castration-resistant prostate cancer (mCRPC) and symptomatic bone metastases.
Presented by Stephen A. Boorjian, MD
The AUA annual meeting’s evolving landscape of advanced prostate cancer treatment session included a talk by Dr. Stephen Boorjian discussing bone health and radionuclide therapy. Dr. Boorjian notes that there are several clinically relevant aspects of bone health in CRPC including (i) the issue of bone loss, given that the median age of patients with CRPC is similar to the age of at-risk patients for physiologic/age-related decrease in bone mineral density
Presented by Silke Gillessen, MD
Beginning with the introduction of docetaxel for metastatic castration resistant prostate cancer (mCRPC) in 2004, there has been a dramatic and rapid proliferation of systemic therapy options in advanced prostate cancer including a number of novel hormonal therapies (including abiraterone acetate and enzalutamide),
Presented by Michael J. Morris, MD
At the 2021 ASCO Dr. Michael Morris and colleagues reviewed the trial design for a phase III study to determine the clinical benefit of docetaxel versus docetaxel and Radium-223 in patients with mCRPC, the DORA trial.
Presented by Adam Kessel, medical student at the University of Utah
In this poster, the authors presented efficacy and safety results from a phase 2 single-center randomized study of enzalutamide monotherapy versus combination enzalutamide and radium-223 in progressive metatstatic castration-resistant prostate cancer (mCRPC)
Presented by Lawrence Mbuagbaw, MD, MPH, Ph.D.
At the 2021 ASCO GU, Dr. Lawrence Mbuagbaw and colleagues presented results of their real-world study evaluating clinical outcomes of patients when Radium-223 was used early (second-line) or late (third or later lines) among men with mCRPC.
Presented by Alexander Meisel, MD
The neutrophil-to-lymphocyte ratio (NLR) could be established as an important prognostic marker for the outcome of metastatic castration-resistant prostate cancer (mCRPC) patients treated with chemotherapy, steroids, and novel androgen receptor directed therapies.
Presented by Catherine H. Marshall, MD, MPH
 Immune modulation may be enhanced by radiation therapy through a variety of mechanisms, including via enhanced display of tumor-associated antigens. Furthermore, radiopharmaceutical agents have been shown to upregulate tumor antigens in prostate cancer models,1
Presented by Silke Gillessen, MD
San Francisco, CA (UroToday.com) Silke Gillessen, MD presented a study comparing two different dosing frequencies of Denusomab in patients with castration-resistant PC, and evaluating the rate of hypocalcemia in the two treatment options.
Presented by Matthew R. Smith, MD, Ph.D.
Munich, Germany (UroToday.com) Radium-223 is an alpha emitter which selectively treats bone metastases with alpha radiation.1 In a recent GU ASCO oral presentation, a radium-223 pharmacodynamic study demonstrated
Presented by Matthew R. Smith, MD, Ph.D.
Munich, Germany (UroToday.com) As has been the trend in management of advanced solid malignancies, there has been increasing interest