Skeletal-related Events In Men Research Articles

Clinical factors associated with prescribing patterns of bone modifying agents in men with metastatic castration-resistant prostate cancer.

e18878 Background: Bone metastases occur in up to 90% of men with metastatic prostate cancer and cause skeletal-related events (SREs) such as fracture and spinal cord compression. Although bone modifying agents (BMAs) have been shown to decrease the risk of SREs in men with metastatic castration-resistant prostate cancer (mCRPC), BMAs are not widely used in this patient population. In this retrospective study, we report the prescribing patterns of BMAs and predictors of BMA use in a large national cohort. Methods: We used the VA corporate data warehouse to identify patients with mCRPC who were treated with first-line mCRPC therapy (abiraterone, enzalutamide, docetaxel, or ketoconazole) between 2010 and 2017. BMA prescribing frequency and patterns were analyzed. Multivariable regression analysis was used to evaluate clinical and disease-specific factors associated with BMA use which are presented as adjusted odds ratios (OR) with 95% confidence intervals (CI). Results: In the final cohort of 4,079 patients, the median age at mCRPC diagnosis was 73 years (IQR 66-81). 29% of patients in the cohort were Black. Diagnosis codes identified bone metastases at mCRPC diagnosis in 48% of the cohort (ICD-9 and 10 coding for sites of metastases are known to underestimate the actual incidence of metastases). Only 48% of patients received a BMA following initiation of treatment for mCRPC, 47% of which had already received a BMA 6 months prior to mCRPC diagnosis. For those who were new BMA starts, the median time to BMA administration from mCRPC treatment was 3.4 months (IQR 1.2-8.8). Factors associated with BMA use were having an ICD-9 or 10 diagnosis code for bone metastases at time of mCRPC treatment (OR 1.28, 95% CI 1.10-1.48), concurrent corticosteroid use (OR 1.90, 95% CI 1.53-2.38), and docetaxel use as first-line mCRPC therapy (OR 1.78, 95% CI 1.45-2.18). Factors associated with decreased BMA use were Charlson comorbidity index score of ≥ 2 (OR 0.75, 95% CI 0.62-0.90), advancing age (OR 0.86 per 10 years, 95% CI 0.79-0.94), and decreased eGFR (eGFR 30-59, OR 0.81, 95% CI 0.68-0.96; eGFR 0-29, OR 0.23, 95% CI 0.14-0.37). Having a diagnosis code for a SRE before mCRPC diagnosis (e.g., bone fracture and cord compression) did not impact BMA use, but the incidence of those events was low. Conclusions: Less than half of this VA cohort received a BMA after starting therapy for mCRPC. Key factors associated with BMA use were corticosteroid use and first-line docetaxel use, which likely represented more aggressive disease. Notably, patients who were older and had more comorbid conditions were less likely to receive a BMA despite being highest risk for frailty and SREs. Future quality improvement efforts aimed at increasing BMA use may address the needs of the geriatric mCRPC patient population.

Comparison of 99m Tc-methylenediphosphonate and 68 Ga-BPAMD PET/computed tomography imaging in bone metastasis.

Bone is considered as the third most common site of metastases, besides lung and liver. Early detection of skeletal metastases aids in better management of skeletal-related events. In the present study cold kit-based 2,2 ' ,2 '' -(10-(2-((diphosphonomethyl)amino)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid (BPAMD) was labeled with 68 Ga. The radiolabeling parameters and clinical evaluation in patients with suspected bone metastases were compared with routinely used 99m Tc-methylenediphosphonate ( 99m Tc-MDP). The kit components of MDP were incubated with at room temperature for 10 min, followed by radiochemical purity testing using thin-layer chromatography. For radiolabeling of BPAMD, the cold kit components reconstituted in 400 μL of HPLC grade water were transferred and incubated with 68 GaCl 3 in the reactor vessel of the fluidic module at 95°C for 20 min. Radiochemical yield and purity were determined with instant thin-layer chromatography using 0.5 M sodium citrate as mobile phase. For clinical evaluation, patients ( n = 10) with suspected bone metastases were enrolled. 99m Tc-MDP and 68 Ga-BPAMD scans were performed on two different days in random order. Imaging outcomes were noted and compared. Radiolabeling of both tracers is facile using cold kit, although BPAMD requires heating. The radiochemical purity was observed to be greater than 99% for all preparations. Both MDP and BPAMD detected skeletal lesions; however, additional lesions were detected in total of seven patients which were not visualized clearly on 99m Tc-MDP scan. BPAMD can be easily tagged with 68 Ga using cold kits. The radiotracer is suitable and efficient for detection of bone metastases using PET/computed tomography.

Bone Health Management in the Continuum of Prostate Cancer Disease.

Simple SummaryIn this review, we summarize the risk factors of prostate cancer (PCa), mechanism of PCa induced bone metastasis, current treatments for PCa induced bone metastasis, treatment induced side-effects, management of skeletal-related events and potential future therapeutic options for bone management in the continuum of PCa disease.Prostate cancer (PCa) is the second-leading cause of cancer-related deaths in men. PCa cells require androgen receptor (AR) signaling for their growth and survival. Androgen deprivation therapy (ADT) is the preferred treatment for patients with locally advanced and metastatic PCa disease. Despite their initial response to androgen blockade, most patients eventually will develop metastatic castration-resistant prostate cancer (mCRPC). Bone metastases are common in men with mCRPC, occurring in 30% of patients within 2 years of castration resistance and in >90% of patients over the course of the disease. Patients with mCRPC-induced bone metastasis develop lesions throughout their skeleton; the 5-year survival rate for these patients is 47%. Bone-metastasis-induced early changes in the bone that proceed the osteoblastic response in the bone matrix are monitored and detected via modern magnetic resonance and PET/CT imaging technologies. Various treatment options, such as targeting osteolytic metastasis with bisphosphonates, prednisone, dexamethasone, denosumab, immunotherapy, external beam radiation therapy, radiopharmaceuticals, surgery, and pain medications are employed to treat prostate-cancer-induced bone metastasis and manage bone health. However, these diagnostics and treatment options are not very accurate nor efficient enough to treat bone metastases and manage bone health. In this review, we present the pathogenesis of PCa-induced bone metastasis, its deleterious impacts on vital organs, the impact of metastatic PCa on bone health, treatment interventions for bone metastasis and management of bone- and skeletal-related events, and possible current and future therapeutic options for bone management in the continuum of prostate cancer disease.

Pharmacological Prevention and Management of Skeletal-Related Events and Bone Loss in Individuals with Cancer.

To provide a literature review of the clinical efficacy and safety data of various pharmacological agents used to manage bone health in people affected by cancer. Peer-reviewed articles and research publications identified from PubMed and relevant clinical guidelines were used in this evidence synthesis. Individuals with cancers such as breast and prostate cancers, multiple myeloma, and other malignancies are at a high risk of developing skeletal-related events such as bone fracture, bone metastasis, and osteoporosis. Pharmacologic agents such as bisphosphonates and RANK-L inhibitor (denosumab) are the mainstay therapy options for managing bone health in this population. Nurses and nurse practitioners should be aware of the efficacy data of bisphosphonates and denosumab but also should be well-versed in the appropriate administration of these agents, potential side effect profiles, timely assessment, and interventions to optimize quality of life.

Bone modifying agents in veterans with castration-resistant prostate cancer.

6582 Background: Skeletal related events (SREs) are a known complication for the 80% of men with metastatic prostate cancer who have bone metastases. Previous studies have demonstrated that bone modifying agents (BMAs) such as zoledronic acid and denosumab reduce SREs in men with metastatic castration-resistant prostate cancer who have bone metastases and are now recommended by national guidelines. We sought to investigate factors associated with use of BMAs in Veterans with CRPC across the Veterans Health Administration (VA). Methods: Using the VA Corporate Data Warehouse, consisting of aggregated medical record data from 130 facilities, we used an algorithm previously published to identify men with a diagnosis of castration-resistant prostate cancer (CRPC) based on rising prostate specific antigen (PSA) levels while on androgen deprivation therapy and who received systemic treatment for CRPC with one of the commonly used therapies: abiraterone, enzalutamide, docetaxel, ketoconazole between 2010 and 2017. To account for clustering among facilities, we used a multilevel multivariable logistic regression to determine the association of patient and disease-specific variables on the odds of a patient receiving a BMA after they started treatment for CRPC. Results: Of 4,998 patients with CRPC in our cohort, 2223 (44%) received either zoledronic acid or denosumab at some point after they were initiated on treatment for CRPC. After adjusting for other variables and accounting for a facility, the odds of receiving a BMA decreased by 3% for every additional year of age (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.96-0.98), and decreased significantly with increasing comorbid conditions (OR 0.94, 95% CI 0.72-0.98 for Charlson Comorbidity Index [CCI] of 1; OR 0.69, 95% CI 0.59-0.81 for CCI 2+). Patients who were Black had 25% lower odds of receiving a BMA than patients who were White (OR 0.75, 95% CI 0.65-0.87). PSA at time of CRPC treatment start had a small but not significant effect on receipt of a BMA (OR 1.04, 95% CI 1.00-1.08) for every unit increase of PSA on the log scale. PSA doubling time was not associated with receipt of a BMA. The presence of a diagnosis code for bone metastases was far lower than expected in this cohort of patients with CRPC (40.7%), and thus was not included in the model. We did not expect the presence of bone metastases to vary significantly among the other independent variables. Conclusions: Despite most patients with CRPC historically having bone metastases, less than half of patients with CRPC received a BMA. Patients who are older, had more comorbidities, or were Black were less likely to receive a BMA after starting treatment for CRPC. Understanding factors that lead to different patterns of treatment can guide initiatives toward more guideline-concordant care.

Optimizing skeletal-related events prevention in patients with advanced prostate cancer.

In patients with metastatic castration-resistant prostate cancer (mCRPC), bone is a dominant site of metastasis. Bone metastases often lead to skeletal-related events (SREs), which include pain, spinal cord compression and fractures. The treatment of bone metastases in men with mCRPC aims to improve SRE-free survival, quality of life and clinical outcomes. Effective treatment options include antiresorptive bone-targeted agents such as zoledronic acid and denosumab, and radium-223, a bone-targeting radiopharmaceutical. Although overseas and local guidelines have widely recommended using either zoledronic acid or denosumab for the prevention of SREs in men with mCRPC and associated bone metastases, current evidence suggests that denosumab is superior to zoledronic acid in terms of longer SRE-free time and fewer total SREs observed in patients.

Use of bisphosphonates and other bone supportive agents in the management of prostate cancer-A UK perspective.

To explore the practice and views of uro-oncologists in the UK regarding their use of bone supportive agents in patients with prostate cancer. An expert-devised online questionnaire was completed by members of the British Uro-oncology Group (BUG). Of 160 uro-oncologists invited, 81 completed the questionnaire. Approximately 70% of respondents never use a bone supportive agent in patients with metastatic hormone-naïve prostate cancer on androgen deprivation therapy (ADT). However, use was more frequent in men with metastatic castration-resistant prostate cancer, from first-line treatment onwards. The majority of uro-oncologists do not use a bone supportive agent to prevent skeletal-related events in men with non-metastatic disease unless the individual patient is at an increased risk of osteoporosis. In men with more advanced disease, respondents would use an oral or intravenous (IV) bisphosphonate in 41% and 61% of patients, respectively. Zoledronic acid is the first-choice bone supportive treatment in 77% of cases, with the lack of clinical data cited as a barrier to use for other IV bisphosphonates. Local guidelines also have a significant influence on the use of bone supportive agents, especially with respect to denosumab. Bone mineral density measurement is conducted in approximately 40% of men with ADT exposure of 2 years or longer, or those with metastatic prostate cancer. Uro-oncologists in the UK generally do not use bone supportive agents for men with metastatic hormone-naïve prostate cancer or those with non-metastatic disease. However, increasing the duration of ADT and the presence of castration-resistant metastatic prostate cancer increases use.

MP64-04 IDENTIFYING SKELETAL-RELATED EVENTS FOR PROSTATE CANCER IN ROUTINELY COLLECTED HOSPITAL DATA

You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History II (MP64)1 Apr 2020MP64-04 IDENTIFYING SKELETAL-RELATED EVENTS FOR PROSTATE CANCER IN ROUTINELY COLLECTED HOSPITAL DATA Matthew Parry*, Thomas Cowling, Arunan Sujenthiran, Julie Nossiter, Brendan Berry, Paul Cathcart, Noel Clarke, Heather Payne, Ajay Aggarwal, and Jan van der Meulen Matthew Parry*Matthew Parry* More articles by this author , Thomas CowlingThomas Cowling More articles by this author , Arunan SujenthiranArunan Sujenthiran More articles by this author , Julie NossiterJulie Nossiter More articles by this author , Brendan BerryBrendan Berry More articles by this author , Paul CathcartPaul Cathcart More articles by this author , Noel ClarkeNoel Clarke More articles by this author , Heather PayneHeather Payne More articles by this author , Ajay AggarwalAjay Aggarwal More articles by this author , and Jan van der MeulenJan van der Meulen More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000939.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Non-osteoporotic skeletal-related events (SREs) are clinically important markers of disease progression in prostate cancer. We developed and validated an approach to identify SREs in men with prostate cancer using routinely-collected data. METHODS: Patients diagnosed with prostate cancer between January 2010 and December 2013 were identified in the National Prostate Cancer Audit, based on English cancer registry data. A coding framework was developed based on diagnostic and procedure codes in linked national administrative hospital and routinely-collected radiotherapy data to identify SREs occurring before December 2015. Two coding definitions of SREs were assessed based on whether the SRE codes were paired with a bone metastasis code (‘specific definition’) or used in isolation (‘sensitive definition’). We explored the validity of both definitions by comparing the cumulative incidence of SREs from time of diagnosis according to prostate cancer stage at diagnosis with death as a competing risk. RESULTS: We identified 40,063, 25,234 and 13,968 patients diagnosed with localised, locally advanced and metastatic disease, respectively. Using the specific definition, we found that the 5-year cumulative incidence of SREs was 0.9% in patients with localised disease, 5.4% in patients with locally advanced disease, and 38.8% in patients with metastatic disease. Using the sensitive definition, the corresponding cumulative incidence figures were 8.4%, 13.4%, and 40.7%, respectively. CONCLUSIONS: The comparison of the cumulative incidence of SREs identified in routinely collected hospital data, based on a specific coding definition in patients diagnosed with different prostate cancer stage, supports their validity as a clinically important marker of cancer progression. Source of Funding: M.G.P. was supported by a Doctoral Research Fellowship from the NHS National Institute for Health Research (DRF-2018-11-ST2-036). T.E.C. was supported by the Medical Research Council (MR/S020470/1). B.B. was partly supported by the NHS National Institute for Health Research through an Academic Clinical Fellowship. H.P. was supported by the University College London Hospitals/University College London Comprehensive Biomedical Research Centre. J.v.d.M. was partly supported by the NIHR Collaboration for Leadership in Applied Health Research and Care North Thames at Bart’s Health NHS Trust. The views expressed in this article are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health and Social Care. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e964-e964 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Matthew Parry* More articles by this author Thomas Cowling More articles by this author Arunan Sujenthiran More articles by this author Julie Nossiter More articles by this author Brendan Berry More articles by this author Paul Cathcart More articles by this author Noel Clarke More articles by this author Heather Payne More articles by this author Ajay Aggarwal More articles by this author Jan van der Meulen More articles by this author Expand All Advertisement PDF downloadLoading ...

Identifying skeletal-related events for prostate cancer patients in routinely collected hospital data

BackgroundNon-osteoporotic skeletal-related events (SREs) are clinically important markers of disease progression in prostate cancer. We developed and validated an approach to identify SREs in men with prostate cancer using routinely-collected data. MethodsPatients diagnosed with prostate cancer between January 2010 and December 2013 were identified in the National Prostate Cancer Audit, based on English cancer registry data. A coding framework was developed based on diagnostic and procedure codes in linked national administrative hospital and routinely-collected radiotherapy data to identify SREs occurring before December 2015. Two coding definitions of SREs were assessed based on whether the SRE codes were paired with a bone metastasis code (‘specific definition’) or used in isolation (‘sensitive definition’). We explored the validity of both definitions by comparing the cumulative incidence of SREs from time of diagnosis according to prostate cancer stage at diagnosis with death as a competing risk. ResultsWe identified 40,063, 25,234 and 13,968 patients diagnosed with localised, locally advanced and metastatic disease, respectively. Using the specific definition, we found that the 5-year cumulative incidence of SREs was 1.0 % in patients with localised disease, 6.0 % in patients with locally advanced disease, and 42.3 % in patients with metastatic disease. Using the sensitive definition, the corresponding cumulative incidence figures were 9.0 %, 14.9 %, and 44.4 %, respectively. ConclusionThe comparison of the cumulative incidence of SREs identified in routinely collected hospital data, based on a specific coding definition in patients diagnosed with different prostate cancer stage, supports their validity as a clinically important marker of cancer progression.

Incidence of skeletal-related events in men with castration-resistant prostate cancer.

188 Background: Skeletal-related events (SREs) are common in men with bone metastases and have negative consequences for patients with castration-resistant prostate cancer (CRPC), including pain, reduced quality of life, and increased risk of death. Published data on background rates of SREs in men with CPRC in real-world practice are sparse. Methods: We included men aged ≥ 65 years in the SEER-Medicare database with a prostate cancer diagnosis in 2000-2011 if they had no prior malignancy, had surgical or medical castration, and met protocol-defined criteria for castration resistance. Castration resistance was inferred from subsequent treatment with any of these systemic therapies: abiraterone, cabazitaxel, docetaxel, enzalutamide, mitoxantrone, or sipuleucel-T. The first occurrence of an SRE was identified in Medicare claims using diagnosis or procedure codes for fracture, bone surgery, radiation therapy, or spinal cord compression. We estimated incidence rates (IRs) of SREs in all eligible person-time and stratified by person-time before and after any use of the following bone-targeted agents (BTAs): alendronate, denosumab, ibandronate, pamidronate, risedronate, or zoledronic acid. Results: Of 2,234 men with CRPC (84% white, mean age 76.6 years), 896 (40%) had an SRE during follow-up, with 74% occurring within a year after cohort entry. Overall, the IR of SREs was 3.78 (95% CI, 3.53-4.03) per 100 person-months. The IR of SREs before any BTA use was 4.16 (95% CI, 3.71-4.65) per 100 person-months, and after any use was 3.60 (95% CI, 3.32-3.91) per 100 person-months. Conclusions: In this large cohort of elderly men with CRPC in a real-world setting in the U.S., SREs were common, with most occurring within a year after cohort entry. Although a direct causal interpretation of the difference in rates before and after BTA use is not possible (since confounding by indication and other factors cannot be excluded), further analysis may address at least some potential confounders.

Revisiting the role of bone-modifying agents in the management of metastatic prostate cancer.

Bone metastases are a hallmark of advanced prostate cancer and may drive the morbidity and mortality of the disease in patients with a poor prognosis. The pathogenesis of bone metastasis involves the interaction between cancer cells, normal bone cells and the bone microenvironment. Targeting the bone microenvironment has become a promising therapy for patients with advanced prostate cancer and bone metastasis. This article reviews the use of the antiresorptive bone-targeted agents zoledronic acid and denosumab in the management of skeletal-related events (SREs) in patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastasis. In real-world clinical practice, these agents have been widely prescribed as a concomitant medication to novel mCRPC therapies, such as abiraterone, enzalutamide and radium-223. International guidelines have recommended zoledronic acid or denosumab for the prevention of SREs in patients with bone metastasis from mCRPC. Although there is currently no consensus regarding the optimal sequencing between the bone-targeted agents and novel anti-cancer therapies, future optimal treatments for patients with bone metastasis from prostate cancer may involve the combination of these agents.

PHS32 - Incremental Healthcare Resource use and Costs Associated with Skeletal-Related Events in Patients with Bone Metastases from Solid Tumors

Skeletal-Related Events (SREs) are common in patients with bone metastases (BM) from solid tumors (ST). Guidelines recommend prophylactic therapy for SRE prevention. SREs are associated with poor survival and high costs. The objective was to estimate the additional economic burden of SREs, measured by healthcare resource use (HRU) and costs, in patients with BM from ST. In this retrospective database analysis, adults with ≥1 inpatient or ≥2 outpatient ST diagnosis followed by ≥1 diagnosis of BM between 01/01/2011 and 06/30/2016 were identified from IQVIA’s PharMetrics Plus healthplan claims database. All patients had continuous enrollment for ≥12 months pre-BM date and ≥6 months post-BM date. First SRE date on or after first BM diagnosis was the index date. Patients with SRE(s) were propensity score matched 1:1 to patients without SREs (controls) using pre-index demographic and clinical characteristics, and costs. Patients were followed until the earlier of last enrollment date or 12/31/2016. Per-patient-per-year (PPPY) HRU and costs were measured during follow-up. McNemar’s and Wilcoxon signed-rank tests were conducted to assess HRU and cost differences. A total of 7,030 patients with SREs and 7,030 matched controls were included in the analysis (mean age: 59 years; female: 55%; mean follow up: 19.6 months; prophylactic therapy: 23.6%). Compared to controls, SRE patients had higher proportion and frequency of hospitalizations (70.9% vs. 48.5%; and 2.6 vs. 1.5, respectively) and emergency room visits (59.5% vs. 46.9%; and 1.7 vs. 1.2, respectively), as-well-as higher costs PPPY ($186,620 vs. $121,281); p<0.0001 for all comparisons. Primary cost attributes were hospitalizations and ancillary costs, with additional PPPY costs of $25,370 and $28,573, respectively, for patients with SREs. Higher economic burden was observed in patients with SREs vs. no SREs (1.7 additional hospitalizations and $65,000 additional cost PPPY). Given its high economic burden, management of SREs with prophylactic therapy is important.

Cost-effectiveness in managing skeletal related events in breast cancer: a strategy of less-intense dosing schedule of bone modifying agents.

The introduction of bone-modifying agents (BMA) or skeletal protective agents in the mid 1990’s into oncology armamentarium has revolutionized the management of skeletal related events (SREs) in cancer patients with established bone metastases. The health and financial burden of SREs are significantly reduced with the use of adjuvant BMAs.

Bone Health and Bone-targeted Therapies for Prostate Cancer: a Programme in Evidence-based Care — Cancer Care Ontario Clinical Practice Guideline

AimsTo make recommendations with respect to bone health and bone-targeted therapies in men with prostate cancer. Materials and methodsA systematic review was carried out by searching MEDLINE, EMBASE and the Cochrane Library from inception to January 2016. Systematic reviews and randomised-controlled trials were considered for inclusion if they involved therapies directed at improving bone health or outcomes such as skeletal-related events, pain and quality of life in patients with prostate cancer either with or without metastases to bone. Therapies included medications, supplements or lifestyle modifications alone or in combination and were compared with placebo, no treatment or other agents. Disease-targeted agents such as androgen receptor-targeted and chemotherapeutic agents were excluded. Recommendations were reviewed by internal and external review groups. ResultsIn men with prostate cancer receiving androgen deprivation therapy, baseline bone mineral density testing is encouraged. Denosumab should be considered for reducing the risk of fracture in men on androgen deprivation therapy with an increased fracture risk. Bisphosphonates were effective in improving bone mineral density, but the effect on fracture was inconclusive. No medication is recommended to prevent the development of first bone metastasis. Denosumab and zoledronic acid are recommended for preventing or delaying skeletal-related events in men with metastatic castration-resistant prostate cancer. Radium-223 is recommended for reducing symptomatic skeletal events and prolonging survival in men with symptomatic metastatic castration-resistant prostate cancer. ConclusionsThe recommendations represent a current standard of care that is feasible to implement, with outcomes valued by clinicians and patients.

Factors predicting skeletal-related events in patients with bone metastatic castration-resistant prostate cancer.

Skeletal-related events (SREs) are common complications of bone metastatic castration-resistant prostate cancer (mCRPC). To the authors' knowledge, there are limited data regarding which factors predict SREs. The authors identified risk factors for SREs in men with bone mCRPC using characteristics commonly available in the medical record. Data from 454 patients with nonmetastatic CRPC were identified from 2 Veteran Affairs Medical Centers from 2000 through 2013. Among these men, 233 (51%) developed bone metastases during follow-up and represented the study cohort. First occurrence of an SRE was abstracted from the medical records. A stepwise multivariable Cox model was used to select the strongest predictors of time to SRE. The median age of the patients at the time of diagnosis of bone mCRPC was 75 years (interquartile range, 68-81 years), and there were 153 nonblack patients (66%). During follow-up (median, 7.8 months [interquartile range, 2.9-18.3 months]), 88 patients (38%) had an SRE. On univariable analysis, more recent year of metastasis (hazard ratio [HR], 0.91), prostate-specific antigen doubling time of ≥9 months versus <9 months (HR, 0.50), and bone pain (HR, 3.34) were all found to be associated with SRE risk. On multivariable analysis, year of metastasis (HR, 0.93), biopsy Gleason score of 7 versus ≤6 (HR, 1.74), radiotherapy as the primary localized treatment versus none (HR, 2.33), and bone pain (HR, 3.64) were associated with SRE risk. The area under the curve for a multivariable model based upon these risk factors was 0.744. The authors identified several significant predictors of SREs among men with mCRPC. In particular, men with bone pain are at high risk of an SRE. If confirmed, future trials should focus on prolonging life and reducing SRE risk in patients with mCRPC with bone pain. Cancer 2017;123:1528-1535. © 2017 American Cancer Society.

Palliative care issues in advanced urological malignancies

Urological malignancies are traditionally affecting people of older age, may not be upfront lethal, especially prostate cancer (PCa), and as a result urological patients often live many years with their disease. Recent advancement in the treatment of castration-resistant PCa have resulted in a prolongation of survival and an improvement in the quality of life even for of patients with advanced disease. The availability of new treatments that prolong life for cancer patients might result in an increase in the need for palliative care procedures as patients live longer and may suffer the side effects of treatment as well as the sequella of their underlying malignancy. This rather extensive review article will review the various palliative treatments available for the most common consequences and complications of genitourinary cancers. One of the most frequent everyday issues that will be discussed is the optimal management of upper urinary tract obstruction caused by malignancy. There has been considerable debate over whether stent placement or percutaneous nephrostomy (PCN) provides better patient care in terms of drainage, preservation of renal function and quality of life. Preservation of bone health and management of skeletal related events will be discussed along with the management of lower urinary tract obstruction by either indwelling or intermittent catheterization for patients with bladder outlet obstruction (BOO) will. The available options and the benefits and drawbacks of catheters versus urethral stents will be discussed in detail. The problems of recurrent intractable hematuria and paraneoplastic syndromes (PNSs) will be addressed as they greatly affect quality of life by requiring repeat hospital admissions.

Cost–effectiveness of denosumab as a bone protective agent for patients with castration resistant prostate cancer

Fortunately, novel agents are nowadays available for the management of patients with castration-resistant prostate cancer (CRPC). Denosumab is a new bone-protective agent, approved for the prevention and management of skeletal-related events. Studies have demonstrated that denosumab has better efficacy and similar rate of adverse effects in comparison with zoledronic acid, which was the standard bone-protective agent. In the present review we study the cost–effectiveness of denosumab in patients with CRPC.

PCN299 - The Clinical and Economic Burden of Skeletal Related Events in Austria, Czech Republic, Germany, Greece, Italy, Spain and Switzerland: A Comparison Between the use of Denosumab and Zoledronic acid in Patients With Breast Cancer and Bone Metastases

To estimate the total number of skeletal-related events (SREs) prevented, related hospital burden and direct medical expenditure when denosumab is used instead of zoledronic acid for SRE prevention in seven European countries. A model was developed combining country-specific breast cancer mortality data from the World Health Organization or from local registries, the proportion of metastatic breast cancer patients with bone metastases (BMs) at high risk of developing SREs from published literature, the prevalence of breast cancer with BMs was derived assuming a steady state approach (with incidence equivalent to mortality of metastatic disease), and the average survival for metastatic breast cancer patients from published literature. Annual SRE rates from a European observational retrospective study and the treatment effect observed in a head-to-head clinical trial of denosumab versus zoledronic acid were used to estimate the total number of predicted SREs by treatment option. Country-specific findings from two retrospective studies were used to estimate the total number of hospitalisations, inpatient days and direct medical costs associated with the management of SREs. Across all countries, the estimated prevalence of breast cancer patients with BMs was 87,592 patients: Austria, 3,253; Czech Republic, 3,509; Germany, 37,895; Greece, 4,639; Italy, 27,767; Spain, 7,553; and Switzerland, 2,975. When denosumab was the selected treatment option, 36,324 SREs were estimated to be avoided per year compared with the use of zoledronic acid, which would save 24,110 hospitalisations, 536,551 inpatient days and 206,605,754€ of direct medical costs (2014 costs in €: Austria, 23,890,554; Czech Republic, 5,779,856; Germany, 60,659,628; Greece, 15,941,728; Italy, 39,998,970; Spain, 17,249,548; and Switzerland, 43,085,469). Denosumab’s clinical superiority in the prevention of SREs over zoledronic acid could result in significant savings in the number and duration of hospitalisations, reducing direct medical costs associated with the management of SREs in Europe.

MP78-02 CUMULATIVE INCIDENCE OF SKELETAL RELATED EVENTS IN MEN WITH METASTATIC PROSTATE CANCER BASED ON ALTERNATIVE ALGORITHMS

You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History III1 Apr 2014MP78-02 CUMULATIVE INCIDENCE OF SKELETAL RELATED EVENTS IN MEN WITH METASTATIC PROSTATE CANCER BASED ON ALTERNATIVE ALGORITHMS Abdulla M. Abdulhalim, Eberechukwu Onukwugha, Corinne Woods, Yi Qian, Jorge Arellano, Arun Balakumaran, C. Daniel Mullins, and Arif Hussain Abdulla M. AbdulhalimAbdulla M. Abdulhalim More articles by this author , Eberechukwu OnukwughaEberechukwu Onukwugha More articles by this author , Corinne WoodsCorinne Woods More articles by this author , Yi QianYi Qian More articles by this author , Jorge ArellanoJorge Arellano More articles by this author , Arun BalakumaranArun Balakumaran More articles by this author , C. Daniel MullinsC. Daniel Mullins More articles by this author , and Arif HussainArif Hussain More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.2485AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Skeletal related events (SREs) are common in men with metastatic prostate cancer (mPC). Several algorithms have been proposed to identify SREs when using claims data. Our aim was to determine how key components of algorithms for identifying SREs from claims impact results on cumulative incidence of SREs in men with mPC. METHODS Algorithms for identifying SREs were developed and applied to data for men aged ≥66 years diagnosed with mPC between 2000-2009 in the SEER-Medicare datasets and followed through 12/31/2010 or until they were lost to follow up. Post-diagnosis SREs were identified using claims that indicated spinal cord compression (SCC), pathologic fracture (PF), surgery to bone (SB), or radiation (suggestive of bone palliative radiation, RAD). Two key components defined alternative algorithms: the window length to consolidate SRE claims into events (14-, 21-, and 28-day windows) and the diagnosis and procedure codes used to identify SREs (′conservative′ and ′extended,′ e.g., PF ′conservative′ definition used codes that specifically indicated pathologic fracture and PF ′extended′ definition used codes that indicated any fracture without accidents/falls within 14 days before fracture). The base case algorithm used a ′conservative′ definition with a 21-day window. RESULTS Among 8,997 mPC men, 3,618 (40.2%) experienced an SRE according to the base case algorithm. Among those with an SRE, 2076 (57%) experienced a subsequent SRE. A total of 8,550 SREs were observed during follow up, with RAD, PF, SCC, and SB constituting 57%, 25%, 10%, and 8%, respectively. (Table) Varying the code definition from ′conservative′ to ′extended′ increased the cumulative incidence of SRE by 65% (Range: 15% [RB] - 200% [PF]). Varying the window length ±7 days from the 21-day base case resulted in a 7% change in SRE cumulative incidence (Range: 0.2% [SB] - 10% [RAD]). CONCLUSIONS The estimated cumulative incidence of SREs using claims data is mostly driven by code definition, and to a lesser extent, by window length. Across the 4 SREs, RAD is most affected by window length and PF is most affected by code definition. Investigators using claims to identify SREs should explicitly define their algorithm for SREs, including the algorithm components based on SRE type. SRE Window Length 14 days 21 days 28 days Ext. Cons. Ext. Cons. Ext. Cons. All SREs 16,313 9,845 14,100 8,550 12,926 7,928 Radiation 6,855 (42) 5,910 (60) 5,638 (40) 4,907 (57) 5,073 (39) 4,439 (56) Pathologic fracture 7,342 (45) 2,318 (23) 6,505 (46) 2,125 (25) 5,990 (46) 2,029 (26) Spinal cord compression 1,473 (9) 974 (10) 1,319 (9) 880 (10) 1,226 (10) 823 (10) Surgery to bone∗ 643 (4) 643 (7) 638 (5) 638 (8) 637 (5) 637 (8) Ext.: Extended code definition; Cons.: Conservative code definition All numbers in parentheses are column %. ∗ Only one set of codes was used for surgery to bone © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e920-e921 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Abdulla M. Abdulhalim More articles by this author Eberechukwu Onukwugha More articles by this author Corinne Woods More articles by this author Yi Qian More articles by this author Jorge Arellano More articles by this author Arun Balakumaran More articles by this author C. Daniel Mullins More articles by this author Arif Hussain More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Bone targeted therapies for the prevention of skeletal morbidity in men with prostate cancer

Men with prostate cancer suffer substantially from bone-related complications. Androgen deprivation therapy itself is a cause of loss of bone mineral density and is associated with an increased incidence of osteoporotic fractures. In advanced disease, bone is by far the most common site of metastasis. Complications of bone metastases prominently include pain and the potential for skeletal events such as spinal cord compression and pathologic fractures. Elevated osteoclast activity is an important aspect of the pathophysiology of both treatment-related osteoporosis and skeletal complications due to metastases. The osteoclast is therefore a therapeutic target. Denosumab is a fully human monoclonal antibody to receptor activator of nuclear factor-κ-B ligand that was designed to potently inhibit osteoclast activity and is the central focus of this review. Bisphosphonates, radiopharmaceuticals and systemically-active hormonal agents such as abiraterone acetate and enzalutamide have each been shown to improve skeletal morbidity in specific clinical situations. Denosumab is the only agent that has been shown to prevent osteoporotic fractures in men receiving androgen deprivation therapy and at elevated risk for fracture. It has also demonstrated superiority to the potent bisphosphonate zoledronic acid for the prevention of skeletal-related events in men with castration-resistant prostate cancer metastatic to bone. Efficacy and toxicity data will be discussed.