Incidence Of Skeletal-related Events In Patients Research Articles

Incidence of skeletal-related events in advanced and metastatic prostate cancer patients treated with androgen deprivation therapy in a low- and middle-income country

Context: Skeletal-related events (SREs) occur in men with prostate cancer (CaP) and may result from androgen deprivation therapy (ADT). Aims: The purpose of this study was to determine the incidence of SREs in patients with CaP treated with HT while highlighting the burden of advanced and metastatic CaP in a low- and middle-income country practice. Settings and Design: Eligible cases were newly diagnosed patients with CaP seen at the University of Abuja Teaching Hospital, Abuja, Nigeria between January 2012 and December 2015 with bone metastases and treated with ADT. Subjects and Methods: Data compiled from patient's medical records showed tumor diagnosis, laboratory and radiology results. SREs included spinal cord compression, surgery to bone, pathologic fracture, and radiation to bone. Statistical Analysis Used: The data were analyzed using SPSS version 20 for windows (SPSS INC: Chicago Illinois). Results: Two hundred and nineteen cases of CaP were seen over the period of which 142 (64.8%) cases were first diagnosed as American Joint Committee on Cancer Stage IV CaP and commenced on ADT. More than half the patients on ADT were older >65 years with a mean (standard deviation [SD]) of 68.3 (±9.5) years. Serum prostate-specific antigen range was 1.4–2461.58 ng/ml with a mean (SD) of 113.7 (±288.9) ng/ml. Twenty nine patients (20.5%) had one or more SREs with spinal cord compression (19.1%), pathological fractures (1.4%), and radiotherapy to the affected bone (1.4%) being the most common SREs. ADT was orchiectomy, LHRH, anti-androgens, and complete androgen blockade (orchiectomy plus antiandrogens) in 14 (9.8%), 3 (2.1%), 44 (30.9%), and 81 (57%) patients, respectively. Conclusions: Sixty-five percent of the cases in this series were either advanced or metastatic CaP at first diagnosis majority of whom went on to orchiectomy plus antiandrogens as ADT. This lends credence not only to late presentation and increased morbidity and mortality of CaP in our environment but also to significantly low penetration of radiotherapy services and access to LHRH.

The skeletal-related events of denosumab versus zoledronic acid in patients with bone metastases: A meta-analysis of randomized controlled trials

ObjectiveThe meta-analysis was used to evaluate the skeletal-related events (SREs) and efficacy of denosumab versus zoledronic acid (ZA) in patients with bone metastases. MethodsThe data of this meta-analysis study were searched from PUBMED, EMBASE, Cochrane Library, Web of Science with Conference Proceedings, Elsevier and China National Knowledge Infrastructure (CNKI) databases till August 2017. Two independent reviewers reviewed the reference lists of relevant articles. The fixed-effects model and random-effects model were used to summarize relative estimates and 95% confidence intervals (CIs) according to the heterogeneity of the included studies. ResultsThree randomized controlled trials (RCTs) including 4050 patients were identified in this meta-analysis study. The pooled analysis showed that denosumab could significantly reduce SREs, series SREs [Odds Ratio (OR) = 0.84; 95% CI, 0.74–0.95, I2 = 0%, P = 0.008] in patients with bone metastases as compared with ZA. Similar results of spinal cord compression SRE and surgery to bone SRE were obtained with (OR = 0.84; 95% CI, 0.70–1.01, I2 = 0%, P = 0.07) and (OR = 0.92; 95% CI, 0.78–1.08, I2 = 0%, P = 0.28) separately, radiation to bone SRE (OR = 0.72; 95% CI, 0.46–1.10, I2 = 11%, P = 0.13) and pathological fracture SRE (OR = 0.78; 95% CI, 0.35–1.73, I2 = 25%, P = 0.54) showed similar results, there were no significant difference between denosumab and ZA in patients with bone metastases. ConclusionDenosumab was more effective than ZA in reducing the incidence of SRE in patients with bone metastases.

Incidence of Skeletal-Related Events in Patients With Advanced and Metastatic Prostate Cancer Treated With Hormone Therapy in a Low- and Middle-Income Country

Abstract 16 Background: Skeletal-related events (SREs) are fractures, radiotherapy to bone, or spinal cord compression that occurs concurrently with or after the first bone metastasis in men with prostate cancer (PC) and may result from hormone therapy (HT). In this work, we report the incidence of SREs in patients with PC who are treated with HT and highlight the burden of advanced and metastatic PC in a practice in a low- and middle-income country. Methods: Retrospective data was of newly diagnosed patients with PC with SREs who were treated with androgen deprivation therapy at the University of Abuja Teaching Hospital, Abuja, Nigeria, between January 2012 and December 2015. Results: Of 219 cases reviewed, 142 patients (64.8%) had American Joint Committee on Cancer stage IV PC and so commenced treatment with HT, with > 50% of these patients being older than 65 years (mean [standard deviation], 68.3 [± 9.5] years). Serum prostate-specific antigen range was 1.4 to 2,461.58 ng/mL (mean [standard deviation], 113.7 [± 288.9] ng/mL). Twenty-nine patients (20.5%) had one or more SREs: spinal cord compression (19.1%), pathological fractures (1.4%), and radiotherapy to the affected bone (1.4%) being the most common. Fifty additional patients (35.2%) had bone pain with localization to the lumbosacral spine in > 50% of them, whereas two patients with pathologic fractures had internal fixation and bone radiotherapy, respectively. HT was orchiectomy, luteinizing hormone-releasing hormone agonists (LHRH), antiandrogens, and complete androgen blockade (orchiectomy plus antiandrogens) in 14 (9.8%), 3 (2.1%), 44 (30.9%), and 81 (57%) patients, respectively. Conclusion: That 65% of our patients had advanced or metastatic PC at first diagnosis lends credence to late presentation with increased morbidity and mortality of PC in our environment where penetration of radiotherapy services and access to LHRH is significantly low, as evidenced by patients who had complete androgen blockade that was treated with orchiectomy plus antiandrogens. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST No COIs from either author.

Incidence of skeletal-related events (SREs) among prostate cancer patients.

e16035 Background: Skeletal related events (SREs) occur in men with prostate cancer and may result from both bone metastases and exposure to androgen deprivation therapy (ADT). The objective of this study was to quantify the incidence of SREs in patients with prostate cancer treated with ADT or orchiectomy in clinical practice. Methods: Prostate cancer patients served by Henry Ford Health System (HFHS) were identified via the HFHS tumor registry. Eligible patients were newly diagnosed with prostate cancer between 2004 and 2010 and treated with ADT or orchiectomy. Comprehensive population-based data were compiled using tumor registry with linkages to pharmacy, laboratory results, and healthcare encounter databases. SREs included spinal cord compression, surgery to bone, pathologic fracture and radiation to bone. Disease progression and metastases were identified by medical record review. Results: We identified 702 patients with prostate cancer and receipt of ADT or orchiectomy; 57.6% were >70 years of age and 43.7% were African American. 56.3% of patients were initially diagnosed at AJCC stage II, 9.8% at stage III, 22.1% at stage IV, and 11.8% had missing or unknown stage. A total of 93 patients (13.2%) had one or more SREs: radiation to bone (8.5%) and spinal cord compression (3.1%) were the most common SREs. We then limited the cohort to patients initially diagnosed with or progressing to AJCC stage IV prostate cancer (N=207). Among this group, 47.8% were >70 years of age. The mean time from stage IV diagnosis to end of follow-up was 35.6 months. In this subgroup, 16.4% of patients were initially diagnosed at AJCC stage II, 8.2% at stage III, 69.6% at stage IV, and 5.8% had missing or unknown stage. 57 patients (27.5%) had one or more SREs. Conclusions: Some clinical trials have found 36-41% of high-risk metastatic prostate cancer patients developed SREs during 3 years of follow-up. In this population-based cohort of patients with prostate cancer receiving ADT or orchiectomy and treated in real-world clinical practice, we found the incidence of SREs to be lower than what has been reported in clinical trials. Additional analyses exploring the incidence of SREs in patients diagnosed with metastatic castrate resistant prostate cancer will be presented.

Abstract P2-05-13: Correlation of conventional versus experimental biomarkers of bone turnover and metastasis behaviour with skeletal related events – A biomarker analysis in conjunction with the TRIUMPH study.

Abstract BACKGROUND: Despite considerable variability in patient (pt) risk of skeletal related events (SREs) from bone metastases (BM), all pts are treated using a one size fits all approach, namely the same dose and dosing schedule (q3-4 wk) of IV bisphosphonate (BP). Identification of novel markers of individual SRE risk are thus required to better tailor treatment. TRIUMPH is an ongoing clinical trial evaluating q12 wk IV BP therapy for 1 year, following >3 months of standard q3-4 wk BP, in women with low risk bone metastases [defined by the bone resorption marker C-telopeptide (CTx) levels <600 ng/L]. This sub-study evaluated the utility of novel biomarkers in better predicting SRE risk in this low-risk cohort. METHODS: Seventy-one pts enrolled in TRIUMPH. Pt serum at baseline (69), 6 (67) and 12 (59) wks post-entry were analyzed for CTx and bone-specific alkaline phosphatase (BSAP) as per study protocol. Urine N-telopeptide (NTx) levels and serum levels of transforming growth factor-β (TGF-β), activinA, procollagen type I amino-terminal propeptide (P1NP), and bone sialoprotein (BSP) levels were also assessed by ELISA (for n=63, 63 and 57 patients at baseline, wk 6 and wk 12 respectively). Biomarker levels were correlated with pt parameters including; time to development of BM, previous SREs, and SREs post-study entry using linear regression analysis. Changes in levels of biomarkers from baseline to 6 or 12 weeks were used to calculate odds ratios of coming off study as per protocol (due to either CTx>600 ng/ml or SRE) or of SRE alone using logistic regression analysis. RESULTS: Although baseline CTx and NTx were elevated in pts who went on to develop SREs, this did not reach statistical significance. Baseline activinA trended towards total number of prior SREs (p = 0.07). Baseline TGF-β correlated with duration of BM (p = 0.004). Change in activinA (baseline to week 6) was the only biomarker that trended to predict coming off study early (p = 0.043). Results of other baseline biomarkers and changes in biomarkers from baseline to wk 12 will also be presented. CONCLUSIONS: This study further questions the role of CTx and NTx for driving treatment decisions around de-intensification of BP therapy (Coleman et al. J Clin Oncol 2012, suppl; abstr 511), and highlights the need for novel markers of SRE risk. Baseline levels of activinA was associated with the incidence of SREs in patients with BM and changes in levels from baseline to 6 weeks correlated with coming off study early. These findings warrant future studies in breast cancer pts assessing activinA as a predictor of SRE risk associated with breast cancer bone metastases. This study was supported by grants from the Ontario Institute for Cancer Research with funding from the Government of Ontario, and from the Ontario Chapter of the Canadian Breast Cancer Foundation. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-13.

Serum activinA and TGF-β as biomarkers of breast cancer bone metastasis behavior.

10620 Background: Bisphosphonates (BP) are prescribed to pts with metastatic bone disease every 3-4 weeks regardless of individual risk for skeletal related events (SREs). In an era of personalized medicine this “one size fits all” approach is not appropriate and novel markers of SRE risk are required. TRIUMPH is an ongoing clinical trial evaluating 12 weekly IV BP therapy for 1 year in women with low risk bone metastases from breast cancer (BC) as defined by the bone resorption marker C-telopeptide (CTx,) levels <600 ng/L. This sub-study evaluated the utility of novel biomarkers in better predicting the risk of developing SREs. Methods: Serum obtained from pts at baseline and 6 weeks post-entry were analyzed for tumor growth factor-β (TGF-β) and activinA levels by ELISA (sensitivity ~15-30 pg/ml). Levels were correlated with pt parameters including time to development of bone metastasis, and number of previous SREs using linear regression analysis. Changes in levels of biomarkers from baseline to 6 weeks were used to calculate odds ratios using logistic regression analysis. Results: Baseline activinA correlated with baseline CTx and bone specific alkaline phosphatase (p=0.004 and p<0.0001 respectively). Baseline activinA also correlated with weight (p=0.02), BMI (p=0.007) and trended towards total number of prior SREs (p=0.07). Baseline TGF-β correlated with pt age (p=0.02), weight (0.006), BMI (p=0.0005) and duration of metastatic bone disease (p=0.004), but did not correlate with any other biomarker. Change in activinA (baseline to week 6) was the only biomarker that trended to predict coming off study early (p=0.053) as per protocol (i.e. CTx>600 ng/ml, SREs or pt/physician choice). Conclusions: Baseline levels of activinA trended to predict incidence of SREs in patients with bone metastases, and changes in levels from baseline to 6 weeks trended to predict coming off study early. These findings warrant future studies in BC pts assessing activinA as a predictor of risk associated with breast cancer bone metastases. This study was conducted with the support of the Ontario Institute for Cancer Research through funding provided by the Government of Ontario, and with funding from the Ontario Chapter of the Canadian Breast Cancer Foundation.

Urinary N-telopeptide (uNTx) is an independent prognostic factor for overall survival in patients with bone metastases from castration-resistant prostate cancer

BackgroundIn patients with bone metastases from castration-resistant prostate cancer (CRPC) not pretreated with a bisphosphonate elevated N-telopeptide of type I collagen (uNTx), a marker of bone resorption, predicts skeletal-related events (SRE). The aim of this study was to assess the prognostic value of uNTx for overall survival (OS) and the incidence of SRE in patients with bone metastases from CRPC receiving zoledronic acid. MethodsFrom 2004 to 2007, 94 patients with bone metastases from CRPC receiving zoledronic acid for at least 2 months were screened for uNTx. ResultsMedian age was 66 years (range 46–88). Median serum prostate-specific antigen (PSA) was 66 ng/ml (0–3984) and median uNTx was 19 nmol/mM creatinine (3–489). During follow-up, 38 patients (40%) experienced an SRE. Median OS was 20 months [95% (CI) confidence interval 15–24). In the multivariate analysis, elevated uNTx [hazard ratio (HR) 2.2 (95% CI 1.2–4.0)], serum PSA [HR 2.8 (95% CI 1.6–5.1)], and ECOG performance status were the only independent prognostic factors for OS. Median OS was 12 months (10–16) and 25 months (21–34) in patients with uNTx ≥20 nmol/mM creatinine and in those with uNTx <20 nmol/mM creatinine, respectively. ConclusionAn elevated uNTx level is an independent prognostic factor for OS in patients with bone metastases from CRPC receiving a bisphosphonate.