The natural history of bone metastases in castrate-resistant prostate cancer.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 239-239
Author(s):  
Robert James Pell ◽  
Stephen John Harland
Keyword(s):  
Prostate Cancer ◽  
Spinal Cord ◽  
Bone Metastases ◽  
Cancer Diagnosis ◽  
Pathological Fracture ◽  
Cord Compression ◽  
Castrate Resistant Prostate Cancer ◽  
Skeletal Related Events ◽  
Castrate Resistant ◽  
Resistant State

239 Background: Previous authorities have commented on the lack of data regarding overall prevalence of Skeletal-Related Events (SREs) in Castrate Resistant Prostate Cancer (CRPC) in patients who have not received therapy for SRE prevention. We describe a cohort of 129 patients followed to death. Methods: 129 patients treated with palliative chemotherapy for CRPC at University College Hospital London between 01/01/2006 and 31/12/2010 had retrospective collection of data concerning date of prostate cancer diagnosis, date of CRPC, date of death, date of bone metastasis development, radiotherapy treatment, pathological fracture, bone surgery, and spinal cord compression up until 01/06/2013. Results: Median age at castrate resistant prostate cancer development was 70 years. Overall median time from prostate cancer diagnosis to establishment of castrate-resistant state was 33 months (range 5-223). Median time from castrate-resistant state to death was 23 months (0-99). Only 9/129 patients failed to develop bone metastases. A total of 162 palliative radiotherapy treatments were given to 74 patients. Only 10 radiotherapy treatments occurred prior to the development of castrate-resistant disease, the remaining 152 all occurred after castrate-resistance occurred. Symptomatic pathological fracture occurred 28 times in 22 (17%) patients. One or more surgical interventions for bone disease were carried out in 23 (18%) patients. 27 (21%) patients were treated for spinal cord compression. In total, 352 skeletal-related events occurred in 89 patients. Conclusions: Important skeletal-related events occurred in 69% of patients with mCRPC. It is possible that incomplete follow-up in clinical trials of agents such as bisphosphonates considerably under estimate the effect of the investigational agent. The frequency of pathological long bone fracture suggests current measures to detect prefracture and intervene are inadequate. [Table: see text]

Impact of skeletal-related events on survival in patients with prostate cancer metastatic to bones.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 223-223
Author(s):  
Jean A. McDougall ◽  
Bernardo Haddock Lobo Goulart ◽  
Sean D Sullivan ◽  
Jeannine S. McCune ◽  
Aasthaa Bansal ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Spinal Cord ◽  
Spinal Cord Compression ◽  
Metastatic Prostate Cancer ◽  
Pathological Fracture ◽  
Cord Compression ◽  
Time Dependent ◽  
Risk Of Death ◽  
Skeletal Related Events ◽  
The Impact

223 Background: Skeletal related events (SREs), defined as pathological fracture, spinal cord compression, surgery or radiotherapy to the bone, occur in nearly half of men diagnosed with metastatic prostate cancer. Accurate assessment of the risk of death associated with SREs is important to making decisions about the use of recently approved treatments, which have been shown to decrease the frequency of skeletal events, yet estimating the impact of SREs on survival presents several methodological challenges given the recurrent time-dependent nature of exposure. Methods: A cohort of men >65years of age, diagnosed with prostate cancer and bone metastasis between January 1, 2004 and December 31, 2009 was identified from the Surveillance Epidemiology and End Results (SEER) registries were linked to Medicare Parts A and B claims. The outcome of interest, death from any cause, was ascertained from SEER and survival time was calculated from the date of metastatic prostate cancer diagnosis. Multivariable Cox proportional hazards models treating the occurrence of an SRE as a time-dependent exposure were used to estimate the hazard ratios (HR) and corresponding 95% confidence intervals (CI) for the association between SRE occurrence, number, and type, and death. Results: Among 3,297 men with metastatic prostate cancer, 40% experienced ≥1 SRE during the observational follow-up period (median 19 months). Compared to men who remained SRE-free, cohort members who had ≥1 SREs had a two-fold higher risk of death (HR 2.2, 95% CI 2.0-2.4). Those whose first SRE was a pathological fracture had a 2.7-fold higher risk of death (HR 2.7, 95% CI 2.3-3.1), followed by spinal cord compression (HR 2.1, 95% CI 1.8-2.5), surgery (HR 1.8, 95% CI 1.5-2.2) and radiotherapy (HR 2.2, 95% CI 1.9-2.4). Compared to those experiencing only one SRE, men who experienced a second SRE of any type had double the risk of death (HR 2.2, 95% CI 1.9-2.6). Conclusions: SREs were associated with ≥50% reduction in overall survival. This finding is consistent across different types of SREs and supports using therapies to prevent or treat SREs in patients with prostate cancer metastatic to the bones.

scholarly journals Practical update for the use of bone-targeted agents in patients with bone metastases from metastatic breast cancer or castration-resistant prostate cancer

2020 ◽  
Vol 27 (4) ◽  
Author(s):  
D. Southcott ◽  
A. Awan ◽  
K. Ghate ◽  
M. Clemons ◽  
R. Fernandes
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Metastatic Breast ◽  
Pathologic Fracture ◽  
Dose Schedule ◽  
Cord Compression ◽  
Targeted Agents ◽  
Castration Resistant Prostate Cancer ◽  
Skeletal Related Events ◽  
Breast And Prostate Cancer

Bone metastases are a significant source of morbidity and mortality for patients with breast and prostate cancer. In this review, we discuss key practical themes regarding the use of bone-targeted agents (btas) such as bisphospho­nates and denosumab for managing bony metastatic disease. The btas both delay the onset and reduce the incidence of skeletal-related events (sres), defined as any or all of a need for radiation therapy or surgery to bone, pathologic fracture, spinal cord compression, or hypercalcemia of malignancy. They have more modest benefits for pain and other quality-of-life measures. Regardless of the benefits of btas, it should always be remembered that the palliative management of meta­static bone disease is multimodal and multidisciplinary. The collaboration of all disciplines is essential for optimal patient care. Special consideration is given to these key questions: What are btas, and what is their efficacy? What are their common toxicities? When should they be initiated? How do we choose the appropriate bta? What is the appropriate dose, schedule, and duration of btas?

scholarly journals Current perspectives on bone metastases in castrate-resistant prostate cancer

2018 ◽  
Vol 37 (1) ◽  
pp. 189-196 ◽  
Author(s):  
Christopher Logothetis ◽  
Michael J. Morris ◽  
Robert Den ◽  
Robert E. Coleman
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

Castrate-resistant Prostate Cancer—Recent Advances in Therapy and Future Perspectives

2013 ◽  
Vol 09 (01) ◽  
pp. 16
Author(s):  
Alan J Koletsky ◽  
Keyword(s):  
Prostate Cancer ◽  
Skeletal Metastases ◽  
Bone Microenvironment ◽  
Resistant Disease ◽  
Recent Advances ◽  
Castrate Resistant Prostate Cancer ◽  
Skeletal Related Events ◽  
Castrate Resistant ◽  
The Many

For many years, few therapeutic options were available for the treatment of advanced prostate cancer. Recent advances in our understanding of the molecular biology of prostate cancer, particularly in the transition to castrate resistant disease, have led to the development of more potent and selective endocrine therapies. In addition, elucidation of the many factors in the bone microenvironment that promote the development and subsequent progression of skeletal metastases has led to the discovery of new bone-targeting agents that can delay the onset of skeletal related events and improve quality of life and survival. This review will highlight recently approved novel agents as well as others currently under investigation for the treatment of castrate-resistant prostate cancer (CRPC).

Identifying biomarkers specific to bone metastases in castrate-resistant prostate cancer.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 5092-5092
Author(s):  
Maahum Ali Haider ◽  
Colm Morrissey ◽  
Ilsa Coleman ◽  
Xiaotun Zhang ◽  
Lisha Brown ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

scholarly journals Bone-Targeted Therapies in Metastatic Castration-Resistant Prostate Cancer: Evolving Paradigms

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Joelle El-Amm ◽  
Ashley Freeman ◽  
Nihar Patel ◽  
Jeanny B. Aragon-Ching
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Kinase Inhibitors ◽  
Targeted Agents ◽  
Pain Palliation ◽  
Castration Resistant Prostate Cancer ◽  
Humanized Monoclonal Antibody ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
Overall Survival Benefit

Majority of patients with metastatic castrate resistant prostate cancer (mCRPC) develop bone metastases which results in significant morbidity and mortality as a result of skeletal-related events (SREs). Several bone-targeted agents are either in clinical use or in development for prevention of SREs. Bisphosphonates were the first class of drugs investigated for prevention of SREs and zoledronic acid is the only bisphosphonate that is FDA-approved for this indication. Another bone-targeted agent is denosumab which is a fully humanized monoclonal antibody that binds to the RANK-L thereby inhibiting RANK-L mediated bone resorption. While several radiopharmaceuticals were approved for pain palliation in mCRPC including strontium and samarium, alpharadin is the first radiopharmaceutical to show significant overall survival benefit. Contemporary therapeutic options including enzalutamide and abiraterone have effects on pain palliation and SREs as well. Other novel bone-targeted agents are currently in development, including the receptor tyrosine kinase inhibitors cabozantinib and dasatinib. Emerging therapeutics in mCRPC has resulted in great strides in preventing one of the most significant sources of complications of bone metastases.

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