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mCRPC with Bone Metastasis

Curated by clinicians: educational forums with videos, abstracts and conference information
Videos
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Clinical Conversations by Experts
PEACE-3 Trial Evaluates Radium-223 Plus Enzalutamide in Bone-Metastatic mCRPC - Enrique Gallardo Diaz
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
Bone Health Management for Advanced Prostate Cancer - Fred Saad
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 Commentaries
Peer-reviewed Abstract Supplemental Commentaries
Written by Ronan Flippot, MD, MSc
The VISION trial was the first phase 3 study to demonstrate an overall survival benefit for prostate-specific membrane antigen (PSMA)-targeted radioligand therapy lutetium-177 Lu-PSMA-617 (Lu-PSMA) over the standard of care in patients with castration-resistant prostate cancer previously treated with chemotherapy and second-generation novel hormonal agents (NHA). Following these results, Lu-PSMA has been approved in most European countries in this population.
Written by Dianne Bosch, MD & Maarten J. van der Doelen, MD, PhD
Metastatic castration-resistant prostate cancer (mCRPC) patients with symptomatic skeletal metastases can be treated with radium-223 therapy. This alpha emitter that selectively targets bone metastases was proven to be of clinical benefit in the phase 3 ALSYMPCA trial.
Written by John S. Wang, Terence Wong, Kevin A. Wu, Trey C. Mullikin, Andrew Armstrong
We present the case of a patient with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC) who underwent treatment with lutetium Lu-177 vipivotide tetraxetan (also known as 177Lu-PSMA-617) due to progressive disease despite multiple lines of therapy, including chemotherapy, hormonal therapy, and radiation, encompassing palliative mediastinal and central nervous system radiation.
Conference Coverage
Conference Highlights Written by Physician Scientists
Presented by Enrique Gallardo, MD
 The 2026 GU ASCO annual meeting featured a prostate cancer session and a presentation by Dr. Enrique Gallardo discussing the final overall survival results from the EORTC 1333/PEACE-3 trial assessing enzalutamide with or without radium-223 in metastatic castration resistant prostate cancer (mCRPC).
Presented by Murilo de Almeida Luz, MD
The 2025 Western Section AUA annual meeting featured a prostate cancer session and a presentation by Murilo de Almeida Luz, MD, discussing the impact of bone-protecting agents on outcomes with enzalutamide, with or without radium-223, in asymptomatic/mildly symptomatic patients with bone mCRPC from PEACE-3. PEACE-3 was an ethics-approved international study in 446 patients with mCRPC and bone metastases randomized 1:1 to a combination of enzalutamide + radium-223 versus enzalutamide alone1:
Presented by  Pablo Alvarez Ballesteros, MD
The 2025 European Society of Medical Oncology (ESMO) Annual Congress held in Berlin, Germany, was host to the Poster presentation session. Dr. Pablo Alvarez Ballesteros presented the poster Real-World Experience with Radium-223 in Metastatic Castration-Resistant Prostate Cancer: A Single-Center Retrospective Study.
Presented by Giorgia Bortolus, IRCCS
The 2025 ESMO annual meeting featured a prostate cancer session and a presentation by Dr. Giorgia Bortolus discussing real-world experience with radium-223 in metastatic castration-resistant prostate cancer (mCRPC). Prostate cancer is one of the leading causes of cancer-related morbidity and mortality in men. A significant proportion of patients progress to CRPC, often accompanied by bone metastases, which significantly impact quality of life and are associated with poor prognosis.
Presented by Jabra Zarka, MD
 The 2025 European Society of Medical Oncology (ESMO) Annual Congress, held in Berlin, Germany, was host to the Poster presentation session. Dr. Jabra Zarka presented the poster LuRa: Efficacy and Tolerability of Radium-223 Following [177Lu]Lu-PSMA-617 in Patients with Metastatic Castration-Resistant Prostate Cancer.
Presented by Rana R. McKay, MD
The 2025 ESMO annual meeting featured a prostate cancer session and a presentation by Dr. Rana R. McKay discussing a real-world study assessing bone fractures and prior abiraterone use in men treated with radium-223 and enzalutamide combination for metastatic castration-resistant prostate cancer (mCRPC). The skeleton is the most common metastatic site in men with prostate cancer, and bone metastasis is associated with an increased risk of bone fracture. Radium-223 is the only targeted alpha therapy approved for the treatment of mCRPC with bone metastases and showed improved overall survival and fewer adverse events versus placebo.1
Presented by Louise K. Kostos, MBBS
The 2025 ESMO annual meeting featured a prostate cancer session and a presentation by Dr. Louise K. Kostos discussing the first results of the AlphaBet trial, a phase I/II trial of combined radium-223 and 177Lu-PSMA-I&T in patients with metastatic castration resistant prostate cancer (mCRPC).
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 
Publications
Articles and Abstracts

Prostate-specific membrane antigen (PSMA)-PET was introduced into clinical practice in 2012 and has since transformed the staging of prostate cancer. Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) criteria were proposed to standardise PSMA-PET reporting.

We present the case of a patient with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC) who underwent treatment with lutetium Lu-177 vipivotide tetraxetan (also known as 177Lu-PSMA-617) due to progressive disease despite multiple lines of therapy, including chemotherapy, hormonal therapy, and radiation, encompassing palliative mediastinal and central nervous system radiation.
Metastatic castration-resistant prostate cancer (mCRPC) patients with symptomatic skeletal metastases can be treated with radium-223 therapy. This alpha emitter that selectively targets bone metastases was proven to be of clinical benefit in the phase 3 ALSYMPCA trial.1
The VISION trial was the first phase 3 study to demonstrate an overall survival benefit for prostate-specific membrane antigen (PSMA)-targeted radioligand therapy lutetium-177 Lu-PSMA-617 (Lu-PSMA) over the standard of care in patients with castration-resistant prostate cancer previously treated with chemotherapy and second-generation novel hormonal agents (NHA). Following these results, Lu-PSMA has been approved in most European countries in this population.
IMPORTANCE: Targeted alpha therapy attempts to deliver systemic radiation selectively to cancer cells while minimizing systemic toxic effects and may lead to additional treatment options for many cancer types.
San Francisco, CA (UroToday.com) -- A team of researchers led by Duke Cancer Institute scientists Steven Patierno, Ph.D.; Daniel George, MD; Jennifer Freedman, Ph.D.; Jiaoti Huang, MD, Ph.D. and Amanda Hargrove, Ph.D. have been awarded a Movember Foundation-Prostate Cancer Foundation Challenge Award. The project includes a number of key co-investigators including Terry Hyslop, PhD (Biostatistics), Michael Kelley MD and Megan McNamara MD (key clinical oncology collaborators at the Durham Veterans Administration Hospital), James Abbruzzese, MD (DCI Associate Director for Clinical Research) and Hailiang Hu, PhD (senior scientist in Pathology). Muthana Al Abo, Ph.D., MD, joins the teams as a PCF Young Investigator. The $1 million award will support a two-year project investigating targeting RNA splicing for therapeutic application in race-related aggressive and lethal prostate cancer in African American and Caucasian patients, including Veterans.
San Francisco, CA (UroToday.com) MD Anderson researchers develop a model for spying on prostate cancer and bone dynamics

Scientists at The University of Texas MD Anderson Cancer Center have engineered a system allowing microscopic monitoring and imaging of cancer that has spread to the bone in mice so they can better understand and develop treatment for bone metastasis in humans.
Radium-223 dichloride (Ra-223) is the first bone-targeting agent showing improvement in overall survival in patients with castration-resistant prostate cancer (CRPC) and bone metastases. We aimed to assess feasibility of Ra-223 treatment in patients with metastatic hormone-sensitive prostate cancer (mHSPC).
This article [1] is a comprehensive analysis of 10 prostate cancer patients who received Ra-223-treatments. These patients were imaged with multiple quantitative PET methods according to our own algorithm [2], including fluoro-18-choline-PET and sodium fluoride-18 PET. These patients were additionally treated with multidisciplinary methods, including other radiation therapies. We recently reported an overall survival of 8.4 years in 46 patients of high-risk T3-4NXM1 primarily metastatic prostate cancer [2].

The landscape of metastatic prostate cancer has changed recently with the availability of six new molecules showing an overall survival benefit. The development of compounds able to decrease the rate of complications from bone metastasis has also led to improvements in overall morbidity associated with this disease.

In the previously reported ALSYMPCA trial in patients with castration-resistant prostate cancer and symptomatic bone metastases, overall survival was significantly longer in patients treated with radium-223 dichloride (radium-223) than in patients treated with placebo.

OBJECTIVE - Prostate cancer (PC) is the most common cancer in Western countries. Recent advances in the treatment of metastatic castration resistant prostate cancer (mCRPC) have caused significant pressure on health care budgets.

BACKGROUND - Radium-223 dichloride (radium-223), a first-in-class alpha-emitting radiopharmaceutical, is recommended in both pre- and post-docetaxel settings in patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases based on overall survival benefit demonstrated in the phase 3 ALSYMPCA study.

BACKGROUND - Radium-223 is a bone-targeting radiopharmaceutical that extends survival in mCRPC. Postapproval data are limited, and the value of biochemical and radiologic monitoring during radium therapy is unknown.

Improving options for patients with metastatic castration-resistant prostate cancer (mCRPC) provide latitude in designing treatment plans that meet patients' medical needs and personal goals.

Even when symptoms, such as pain, impose significant impacts on their daily lives, many men with advanced prostate cancer do not report the symptoms to their doctors, according to an international survey of both patients and their caregivers to explore this issue. Symptoms may go unrecognized as being associated with cancer, or men deliberately choose not to speak about them with their doctors. As a result, they may not receive interventions that could ease the discomfort.

BACKGROUND - Radium-223 prolongs overall survival in patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases, regardless of prior docetaxel. Whether or not chemotherapy can be safely administered following radium-223 treatment is of clinical importance.