Bone Metastases In Prostate Cancer Patients Research Articles

Pretreatment level of serum sialic acid predicts both qualitative and quantitative bone metastases of prostate cancer.

Recently, serum sialic acid (SA) has emerged as a distinct prognostic marker for prostate cancer (PCa) and bone metastases, warranting differential treatment and prognosis for low-volume (LVD) and high-volume disease (HVD). In clinical settings, evaluating bone metastases can prove advantageous. We aimed to establish the correlation between SA and both bone metastasis and HVD in newly diagnosed PCa patients. We conducted a retrospective analysis of 1202 patients who received a new diagnosis of PCa between November 2014 and February 2021. We compared pretreatment SA levels across multiple groups and investigated the associations between SA levels and the clinical parameters of patients. Additionally, we compared the differences between HVD and LVD. We utilized several statistical methods, including the non-parametric Mann-Whitney U test, Spearman correlation, receiver operating characteristic (ROC) curve analysis, and logistic regression. The results indicate that SA may serve as a predictor of bone metastasis in patients with HVD. ROC curve analysis revealed a cut-off value of 56.15 mg/dL with an area under the curve of 0.767 (95% CI: 0.703-0.832, P < 0.001) for bone metastasis versus without bone metastasis and a cut-off value of 65.80 mg/dL with an area under the curve of 0.766 (95% CI: 0.644-0.888, P = 0.003) for HVD versus LVD. Notably, PCa patients with bone metastases exhibited significantly higher SA levels than those without bone metastases, and HVD patients had higher SA levels than LVD patients. In comparison to the non-metastatic and LVD cohorts, the cohort with HVD exhibited higher levels of alkaline phosphatase (AKP) (median, 122.00 U/L), fibrinogen (FIB) (median, 3.63 g/L), and prostate-specific antigen (PSA) (median, 215.70 ng/mL), as well as higher Gleason scores (> 7). Multivariate logistic regression analysis demonstrated that an SA level of > 56.15 mg/dL was independently associated with the presence of bone metastases in PCa patients (OR = 2.966, P = 0.018), while an SA level of > 65.80 mg/dL was independently associated with HVD (OR = 1.194, P = 0.048). The pretreatment serum SA level is positively correlated with the presence of bone metastases.

Abstract 1326: Perineural invasion and bone metastases in prostate cancer - is there a link

Abstract Bone metastases are the most common secondary lesions in prostate cancer (PCa) patients. Typically, initial bone metastases develop in the lower part of the spine and pelvis. While this metastatic pattern is not consistent with the random nature of the arterial osseous dissemination, previous reports suggested the role of the retrograde venous spread in this phenomenon. However, clinical data also indicate a positive association between the degree of perineural invasion (PNI) and bone metastases in PCa patients. Yet, the mechanism linking these two means of dissemination remains unknown. To identify the processes involved in the initial PCa dissemination we used the PC3-ML cell line, which was previously shown to trigger bone metastases, in the orthotopic xenograft model. To this end, the cells were injected into the prostates of male SCID/Bg mice and tumor development and progression was followed by magnetic resonance imaging (MRI) and histopathology. MRI indicated local invasion of the primary tumor, which later resulted in the formation of multiple secondary lesions along the lower spine. However, histopathological analysis revealed that these lesions were initiated in the soft tissues surrounding the vertebral column, while the subsequent invasion of the vertebra was the secondary event. The staining for neuronal markers, neurofilament (NF), tyrosine hydroxylase (TH) and neuropeptide Y (NPY), revealed that PCa cells created multicellular clusters spreading longitudinally along the small nerve fibers, particularly in the paraspinal muscle compartment. The staining for the endothelial cell marker, CD31, detected small vessels present within PCa clusters. However, no evident encapsulation of the PCa cells within blood vessels consistent with the retrograde venous spread was observed. Altogether, these results suggest PNI as the main route of the initial local dissemination of the PCa cells toward the bone, which then triggers bone invasion and subsequent hematogenous spread to distant bones. Further mechanistic studies are required to confirm this hypothesis. Citation Format: Dawid Sigorski, Susana Galli, Sung Hyeok Hong, Ewa Iżycka-Świeszewska, Joanna B. Kitlinska. Perineural invasion and bone metastases in prostate cancer - is there a link [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1326.

68Ga-PSMA PET/CT for the evaluation of metastasis in patients with prostate cancer: A systematic review and meta-analysis.

The aim of this study was to assess the diagnostic value of gallium-68-prostate specific membrane antigen (68Ga-PSMA) positron emission tomography/computed tomography (PET/CT) in detecting metastases in prostate cancer (PCa) patients. A comprehensive literature search of studies published before August 2021 in PubMed, Embase and Cochrane Library databases was conducted.The methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Studies investigating the diagnostic value of 68Ga-PSMA PET/CT were selected for qualitative and quantitative analysis. Twenty-five articles using 68Ga-PSMA PET/CT for detecting metastases in PCa patients were selected for qualitative analysis, 16 of which were selected for meta-analysis. The sensitivities of 68Ga-PSMA PET/CT in detecting lymph node metastases ranged from 33.3% to 96.08%, with high specificities ranged from 82% to 100%. Gallium-68-PSMA PET/CT demonstrated outstanding diagnostic performance in PCa patients with bone metastases. Only two articles about 68Ga-PSMA PET/CT for lung metastases showed that the detection value was limited. It was difficult to distinguish lung metastases in PCa patients from benign lesions or primary lung cancer. There was only one article about 68Ga-PSMA PET/CT for liver metastases, which showed that about 77.7% of metastatic lesions will be 68Ga-PSMA-positive and 22.3% will be false negatives. Due to the lack of articles on PCa visceral metastases, we only conducted a meta-analysis on lymph node metastases and bone metastases. In our meta-analysis, the per-patient pooled sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), diagnostic odds ratio (DOR), and the area under the ROC curve (AUC) of lymph node metastases were 0.61, 0.96, 14.4, 0.41, 35, and 0.95, respectively. The per-lesion pooled sensitivity, specificity, LR+, LR-, DOR, and AUC of V were 0.74, 0.99, 76.0, 0.26, 289 and 0.99, respectively. The per-patient pooled sensitivity, specificity, LR+, LR-, DOR, and AUC of bone metastases were 0.97, 1.00, 1100.1, 0.03, 37490 and 0.98, respectively. Gallium-68-PSMA PET/CT demonstrated outstanding diagnostic performance for bone metastases in PCa patients. The majority of lymph node metastases, lung metastases, and liver metastases overexpressed PSMA, which could be directly detected. However, a considerable number of lesions were false negatives.

Application of Machine Learning Techniques to Predict Bone Metastasis in Patients with Prostate Cancer.

ObjectiveThis study aimed to develop and validate a machine learning model for predicting bone metastases (BM) in prostate cancer (PCa) patients.MethodsDemographic and clinicopathologic variables of PCa patients in the Surveillance, Epidemiology and End Results (SEER) database from 2010 to 2017 were retrospectively analyzed. We used six different machine learning algorithms, including Decision tree (DT), Random forest (RF), Multilayer Perceptron (MLP), Logistic regression (LR), Naive Bayes classifiers (NBC), and eXtreme gradient boosting (XGB), to build prediction models. External validation using data from 644 PCa patients of the First Affiliated Hospital of Nanchang University from 2010 to 2016. The performance of the models was evaluated using the area under receiver operating characteristic curve (AUC), accuracy score, sensitivity (recall rate) and specificity. A web predictor was developed based on the best performance model.ResultsA total of 207,137 PCa patients from SEER were included in this study. Of whom, 6725 (3.25%) developed BM. Gleason score, Prostate-specific antigen (PSA) value, T, N stage and age were found to be the risk factors of BM. The XGB model offered the best predictive performance among these 6 models (AUC: 0.962, accuracy: 0.884, sensitivity (recall rate): 0.906, and specificity: 0.879). An XGB model-based web predictor was developed to predict BM in PCa patients.ConclusionThis study developed a machine learning model and a web predictor for predicting the risk of BM in PCa patients, which may help physicians make personalized clinical decisions and treatment strategy for patients.

Correlation Between the Prostate-Specific Antigen Level and Bone Metastasis in Prostate Cancer. (Retrospective Study)

Background: The most common non-cutaneous malignancy for men is Prostate cancer (PCa). PCa diagnosed by biopsy and PSA detection. Bone metastasis (BM) causes a lot of complications, such as bone pain and pathological fracture that cause overall compromised quality of life. Bone scintigraphy (BS) is commonly used for monitoring and detection of (BM). Objective: To correlate between serum PSA level and BM in PCa patients on series of 250 patients through detecting PSA levels and BSs. Patients and Methods: In the present study Patients were stratified (group A) &amp; (group B) according to BM. Out of the 250 patients, 180 patients (Group A localized PCa) were with age range from 57 -92 years, the remaining 70 patients (Group B metastasis PCa) the age range was 53-88 years. Prostate specific antigen (PSA) level for both groups were detected. Results: By comparing group A and group B there was a highly significant difference in PSA value in favor of positive BS group (p-value &lt; 0.001). The present study recommends BS in asymptomatic patients with PSA above 60 Ng/ml. Conclusion: PCa is the most common malignant non-cutaneous tumor for men. The most common spread for PCa is bone spread. Age doesn’t correlate with BM in PCa patients. PSA total show highly significance with BM in PCa patients. PSA cut-off value for BM in PCa patients was 60 Ng/ml so it was recommended to perform BS for asymptomatic patients with PSA total above 60 Ng/ml.

Correlation Between the Prostate-Specific Antigen Level and Bone Metastasis in Prostate Cancer. (Retrospective Study)

Background: The most common non-cutaneous malignancy for men is Prostate cancer (PCa). PCa diagnosed by biopsy and PSA detection. Bone metastasis (BM) causes a lot of complications, such as bone pain and pathological fracture that cause overall compromised quality of life. Bone scintigraphy (BS) is commonly used for monitoring and detection of (BM). Objective: To correlate between serum PSA level and BM in PCa patients on series of 250 patients through detecting PSA levels and BSs. Patients and Methods: In the present study Patients were stratified (group A) &amp; (group B) according to BM. Out of the 250 patients, 180 patients (Group A localized PCa) were with age range from 57 -92 years, the remaining 70 patients (Group B metastasis PCa) the age range was 53-88 years. Prostate specific antigen (PSA) level for both groups were detected. Results: By comparing group A and group B there was a highly significant difference in PSA value in favor of positive BS group (p-value &lt; 0.001). The present study recommends BS in asymptomatic patients with PSA above 60 Ng/ml. Conclusion: PCa is the most common malignant non-cutaneous tumor for men. The most common spread for PCa is bone spread. Age doesn’t correlate with BM in PCa patients. PSA total show highly significance with BM in PCa patients. PSA cut-off value for BM in PCa patients was 60 Ng/ml so it was recommended to perform BS for asymptomatic patients with PSA total above 60 Ng/ml.

Serum ProGRP as a novel biomarker of bone metastasis in prostate cancer

BackgroundThe prognosis of prostate cancer (PCa) is related to tumor metastasis, among which 80% were bone metastasis. In this study, we investigated the correlation between diverse clinical factors and bone metastasis in PCa patients and identified potential biomarkers of bone metastasis in PCa patients. MethodsThe clinical data of 150 PCa patients were reviewed consecutively from January 2015 to March 2020 in this study. The relationships between clinical characteristics, serum biomarkers and bone metastasis in PCa patients were analyzed, respectively. Multivariate logistic regression analysis was applied to identify potential markers of bone metastasis in prostate cancer. Receiver operating characteristic (ROC) curve was used to explore the diagnostic values of potential biomarkers. ResultsCompared with the PCa patients without bone metastasis, the serum levels of CA-125, T-PSA, F-PSA, CYFRA21-1 and ProGRP were significantly elevated in PCa patients with bone metastasis. Multivariate logistic regression analysis showed that T-PSA (OR 1.014, P = 0.021), F-PSA (OR 1.124, P = 0.016) and Pro-gastrin-releasing peptide (ProGRP) (OR 1.057, P = 0.026) were significantly associated with the bone metastasis of PCa patients. ROC curves indicated that T-PSA, F-PSA and ProGRP could effectively discriminate bone metastasis from non-bone metastasis PCa patients, and the AUCs (area under the curves) were 0.885, 0.919 and 0.752, respectively. According to the Youden index, the cut-off values of T-PSA, F-PSA and ProGRP were defined as 56.50 ng/ml, 6.96 ng/ml and 31.60 pg/ml, respectively. T-PSA, F-PSA and ProGRP produced a sensitivity of 78.30%, 81.70% and 61.70%, a specificity of 93.30%, 88.90% and 82.20%, respectively. The AUC for the combination of T-PSA, F-PSA with ProGRP was 0.941 with 90.00% sensitivity, much better than that of any single biomarker or two biomarkers combinate. ConclusionsSerum ProGRP might be a potential tumor marker of bone metastasis in prostate cancer, which may contribute to the early diagnosis of bone metastasis when used alone or in combination with other commonly used biomarkers.

Prognosis of prostate cancer and bone metastasis pattern of patients: a SEER-based study and a local hospital based study from China

Prostate cancer (PCa) is the leading cause of cancer-related death among men worldwide. Knowledge of the prognostic factors of PCa and the bone metastasis pattern of patients would be helpful for patients and doctors. The data of 177,255 patients with prostate cancer diagnosed between 2010 and 2013 with at least five years of follow-up were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate Cox regression analysis was used to determine the predictive value of patients’ characteristics for survival after adjusting for other variates. Multivariate logistic regression analysis was used to evaluate the odds ratio of bone metastasis in PCa patients. The predictive value of age, race, marital status, and tumor characteristics were compared. The survival of patients with different socioeconomic statuses and bone metastasis statuses was compared by Kaplan–Meier analysis. A total of 1,335 patients with prostate cancer diagnosed between 2009 and 2015 were enrolled from the Second Affiliated Hospital of Zhejiang University School of Medicine. The survival of patients with different prostate-specific antigen (PSA) levels, Gleason scores, marital statuses and bone metastasis statuses was compared by Kaplan-Meier analysis. In SEER database, 96.74% of patients were 50 years of age or older. Multivariate Cox analysis revealed that for PCa patients, age at presentation, older age, single marital status, lower socioeconomic status, higher PSA level, T1 and N0 stage, and bone metastasis were independent risk factors for increased mortality. Multivariate logistic regression analysis revealed that patients who were married, were living in urban areas, had lower PSA levels, underwent surgery, and radiation had lower OR factors for bone metastasis. Asian or Pacific Islander, better socioeconomic status, lived in urban areas, married marital status, lower PSA levels and lower Gleason scores were better prognostic factors in PCa. Additionally, patients with single or divorced marital status, who were living in rural places had higher PSA levels, and T1 and N0 stages have a high OR for bone metastasis.

Elevated Serum Sialic Acid Levels Predict Prostate Cancer As Well As Bone Metastases.

Objective: To evaluate the value of serum sialic acid (SA) in diagnosis of benign prostatic hyperplasia (BPH), prostate cancer (PCa), and bone metastases in PCa patients.Materials and Methods: Data from 540 patients who were newly diagnosed with PCa or BPH between November 2014 and March 2018 were retrospectively collected and analyzed. Pretreatment SA levels were compared across various groups, then, associations between SA levels and clinic parameters of patients were analyzed as well. Univariate and multivariate logistic regression analyses were further used to identify independent associations.Results: The mean SA levels in patients with PCa were significantly higher than with BPH (p = 0.013). Furthermore, PCa patients with bone metastases showed elevated SA levels compared with PCa without bone metastases (p < 0.001). A multivariate logistic regression model showed that: SA level > 52.35 mg/dL was identified to be independently associated with the diagnosis of PCa (HR = 1.645, p = 0.036), and SA level > 59 mg/dL was identified to be independent association with the presence of bone metastases in PCa patients (HR = 6.421, p = 0.012).Conclusions: Elevated SA level is an independent predictor of prostate cancer as well as its bone metastases. Therefore, SA level may be a promising diagnostic and prognostic biomarker for prostate cancer and bone metastases.

Role of Neutrophil to Lymphocyte Ratio or Platelet to Lymphocyte Ratio in Prediction of Bone Metastasis of Prostate Cancer.

Accumulating evidence has revealed that inflammation might play an important role in the genesis and development of cancer. High levels of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ration (PLR) are parameters of systemic inflammation which have been identified to be associated with poor prognosis in PCa. Bone is one of the most common sites of metastasis from prostate cancer; however, there are few studies concerning the correlation of NLR, PLR, and bone metastases in PCa. The aim of this study was to evaluate the performance of neutrophil to lymphocyte ratio (NLR) or platelet to lymphocyte (PLR) in diagnosis of bone metastasis of prostate cancer (PCa). Data of 74 PCa patients without metastases, 51 PCa patients with bone metastases, and 43 patients with benign prostatic hypertrophy (BPH) were retrospectively reviewed. The difference of patients' clinical and laboratory characteristics of the three groups was comparatively studied. ROC analysis was used to evaluate the benefit of adding NLR or PLR to prostate specific antigen (PSA) in prediction of bone metastases. Depending on this cutoff value, patients were divided into high-NLR or low-NLR group, high-PLR or low-PLR group. There were significant differences in NLR and PLR between groups with bone metastases and without bone metastases (p = 0.044; p = 0.030), while there was no significant difference between NLR and PLR of the patients with localized prostate cancer and BPH (p = 0.462; p = 0.102). NLR and PLR were correlated with PSA level in the patients with prostate cancer (p = 0.006, r = 0.247; p = 0.025, r = 0.200). The distribution of PSA showed significant differences between the high-NLR and low-NLR group, as well as between the high-PLR and low-PLR group. By applying the ROC curve method, the AUC values of PSA with NLR or PLR were 0.725 and 0.838 (0.763 - 0.913), respectively. Although PSA + PLR had the largest area, there was no statistical significance between PSA + PLR and PSA (p = 0.6992). NLR and PLR significantly increase in PCa patients with bone metastases and are valuable in the diagnosis of bone metastases in PCa patients.

Palliative radiation therapy (RT) for prostate cancer patients with bone metastases at diagnosis: A hospital-based analysis of patterns of care, RT fractionation scheme, and overall survival.

Prostate cancer (PCa) is one of the most common malignancies associated with bone metastases, and palliative radiation therapy (RT) is an effective treatment option. A total of 2641 patients were identified with PCa and bone metastases at diagnosis from 2010 to 2014 in the NCDB. Fractionation scheme was designated as short course ([SC‐RT]: 8 Gy in 1 fraction and 20 Gy in 5 fractions) vs long course ([LC‐RT]: 30 Gy in 10 fractions and 37.5 Gy in 15 fractions). Patient characteristics were correlated with fractionation scheme using logistic regression. Overall survival was analyzed using the Kaplan‐Meier method, log‐rank test, Cox proportional hazards models, and propensity score‐matched analyses. A total of 2255 (85.4%) patients were included in the LC‐RT group and 386 (14.6%) patients in the SC‐RT group. SC‐RT was more common in patients over 75 years age (odds ratio [OR]: 1.70, 95% confidence interval [CI] 1.32‐2.20), treatment at an academic center (OR: 1.76, 1.20‐2.57), living greater than 15 miles distance to treatment facility (OR: 1.38, 1.05‐1.83), treatment to the rib (OR: 2.99, 1.36‐6.60), and in 2014 (OR: 1.73, 1.19‐2.51). RT to the spine was more commonly long course (P < .0001). In the propensity‐matched cohort, LC‐RT was associated with improved OS (P < .0001), but no OS difference was observed between 37.5 Gy and either 8 Gy in one fraction or 20 Gy in 5 fractions (P > .5). LC‐RT remains the most common treatment fractionation scheme for palliative bone metastases in PCa patients. Use of palliative SC‐RT is increasing, particularly in more recent years, for older patients, treatment at academic centers, and with increasing distance from a treatment center.

Multi-field-of-view SPECT is superior to whole-body scanning for assessing metastatic bone disease in patients with prostate cancer.

The aim of this study was to compare the diagnostic performance of whole-body bone scintigraphy (WBS) and multi-field-of-view single photon emission tomography (multi-FOV SPECT) with 99mTc-oxidronate (99mTc-HDP) in patients with prostate cancer (PCa). In a prospective study, WBS and SPECT acquisitions were performed in 194 patients with histologically confirmed PCa and serum prostate-specific antigen (PSA) levels above 10 ng/mL. Scans obtained using the two modalities were interpreted separately. Clinical and biochemical follow-up, radiological studies and biopsies served as benchmarks for the assessments. The impact of PSA level on WBS and SPECT results was also evaluated. The patient-based sensitivity, specificity, accuracy, PPV and NPV values of SPECT examinations were higher than those of WBS, especially in patients with serum PSA levels <40 ng/mL. Multi-FOV SPECT proved to be more sensitive and specific than WBS in detecting bone metastases in PCa patients.

Comparison of hybrid 68Ga-PSMA-PET/CT and 99mTc-DPD-SPECT/CT for the detection of bone metastases in prostate cancer patients: Additional value of morphologic information from low dose CT.

This study compared 68Gallium-prostate-specific-membrane-antigen based Positron-emission-tomography (68Ga-PSMA-PET) and 99metastabletechnetium-3,3-diphospho-1,2-propanedicarbonacid (99mTc-DPD-SPECT) in performing skeletal staging in prostate cancer (PC) patients and evaluated the additional value of the information from low-dose-computed tomography (CT). In this retrospective study, 54 patients who received 68Ga-PSMA-PET/CT and 99mTc-DPD-SPECT/CT within 80 days were extracted from our database. Osseous lesions were classified as benign, malignant or equivocal. Lesion, region and patient based analysis was performed with and without CT fusion. The reference standard was generated by defining a best valuable comparator (BVC) containing information from all available data. In the patient based analysis, accuracies measured as "area-under-the-curve" (AUC) for 68Ga-PSMA-PET, 99mTc-SPECT, 68Ga-PSMA-PET/CT and 99mTc-SPECT/CT were 0.97-0.96, 0.86-0.83, 1.00 and 0.83, respectively (p<0.05) (ranges = optimistic vs. pessimistic view). Region based analysis resulted in the following sensitivities and specificities: 91.8-97.7%, 100-99.5% (PET); 61.2-70.6%, 99.8-98.3% (SPECT); 97.7%, 100% (PET/CT), 69.4% and 98.3% (SPECT/CT) (p<0.05). The amount of correct classifications of equivocal lesions by CT was significantly higher in PET (100%) compared to SPECT (52.4%) (p<0.05). 68Ga-PSMA-PET outperforms 99mTc-DPD-SPECT in detecting bone metastases in PC patients. Additional information from low-dose-CT resulted in a significant reduction in equivocal lesions in both modalities, however 68Ga-PSMA-PET benefited most. • Ga-PSMA-PET outperforms 99m Tc-DPD-SPECT in skeletal staging in prostate cancer patients • Proportion of equivocal decisions was significantly reduced by CT-fusion in both modalities • Ga-PSMA-PET benefits more from CT information, compared to 99m Tc-DPD-SPECT.

68Ga]PSMA-HBED-CC Uptake in Osteolytic, Osteoblastic, and Bone Marrow Metastases of Prostate Cancer Patients.

The aim of this study was to evaluate potential differences in "Glu-NH-CO-NH-Lys" radio-labeled with [68Ga]gallium N,N-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N-diacetic acid ([68Ga]PSMA-HBED-CC) uptake in osteolytic, osteoblastic, mixed, and bone marrow metastases in prostate cancer (PC) patients. This retrospective study was approved by the local ethics committee. Patients who received [68Ga]PSMA-HBED-CC positron emission tomography/computed tomography ([68Ga]PSMA-PET/CT) with at least one positive bone metastasis were included in this study. Only patients who have not received systemic therapy for their PC were included. Bone metastases had to be confirmed by at least one other imaging modality or follow-up investigation. The maximum standardized uptake value (SUVmax) and mean Hounsfield units (HUmean) of each metastasis were measured. Based on CT, each metastasis was classified as osteolytic (OL), osteoblastic (OB), bone marrow (BM), or mixed (M). One hundred fifty-four bone metastases in 30 patients were evaluated. Eighty out of 154 (51.9%) metastases were classified as OB, 21/154 (13.6%) as OL, 23/154 (14.9%) as M, and 30/154 (19.5%) as BM. The SUVmax for the different types of metastases were 10.6±7.07 (OB), 24.0±19.3 (OL), 16.0±21.0 (M), and 14.7±9.9 (BM). The SUVmax of OB vs. OL and OB vs. BM metastases differed significantly (p≤0.025). A significant negative correlation between HUmean and SUVmax (r=-0.23, p<0.05) was measured. [68Ga]PSMA-HBED-CC uptake is higher in osteolytic and bone marrow metastases compared to osteoblastic metastases. Information derived from [68Ga]PSMA-PET and CT complement each other for the reliable diagnosis of the different types of bone metastases in PC patients.

Discordance rate between radiolabelled choline PET/CT and bone scintigraphy in detecting bone metastases in patients with prostate cancer: a meta-analysis

The objective of the study was to systematically review published data and perform a meta-analysis about the discordance rate between radiolabelled choline PET/CT and bone scintigraphy (BS) in detecting bone metastases in patients with prostate cancer (PCa). A comprehensive literature search of studies or subsets of studies published through November 2014 including information on the comparison among radiolabelled choline PET/CT and bone scintigraphy in PCa patients was carried out. A meta-analysis was performed in order to calculate the pooled discordance rate among these methods in detecting bone metastases on a per patient-based analysis. Twelve articles were selected. The pooled discordance rate among radiolabelled choline PET/CT and BS in detecting bone metastases was 10.9 % (95 % confidence interval 6.3–16.7 %). Discordant findings were due to radiolabelled choline positive and BS negative or inconclusive findings, but BS positive and radiolabelled choline-negative findings also occurred. We discuss the possible causes of discordant findings. Discordance rate between radiolabelled choline PET/CT and BS in detecting bone metastases in PCa patients is not negligible and both methods are useful in this setting.

Association ofXPCGene Polymorphisms with Susceptibility to Prostate Cancer: Evidence from 3,936 Subjects

Polymorphisms of xeroderma pigmentosum complementation group C (XPC) are thought to have significant effects on prostate cancer (PCa) risk. The aim of our study was to evaluate the impact of XPC gene polymorphisms on PCa risk by using a meta-analysis. Data were collected from the following electronic databases: PubMed, EMBASE, Elsevier Science Direct, Cochrane Library, and CNKI, with the last report up to April 30, 2013. Odds ratios with 95% confidence intervals were used to assess the strength of the association. A total of five separate case-control studies (1966 cases and 1970 controls) were included in this meta-analysis. Meta-analysis was performed for the rs2228001 and PAT+/-polymorphisms. We did not detect a significant association between rs2228001 polymorphism and PCa (p>0.05). Similar results were found in stratification analyses by ethnicity and tumor stage. We detected a significant association of PAT+/-polymorphism with PCa (p<0.05). In stratification analysis, we did not detect a significant association of PAT+/-polymorphism with risk of bone metastasis in PCa patients (p>0.05). These analyses suggest that XPC gene PAT+/-polymorphism, but not rs2228001, likely contributes to susceptibility to PCa.

Multi-field-of-view SPECT is superior to whole-body scanning for assessing metastatic bone disease in patients with prostate cancer

The aim of this study was to compare the diagnostic performance of whole-body bone scintigraphy (WBS) and multi-field-of-view single photon emission tomography (multi-FOV SPECT) with 99mTc-oxidronate (99mTc-HDP) in patients with prostate cancer (PCa). In a prospective study, WBS and SPECT acquisitions were performed in 194 patients with histologically confirmed PCa and serum prostate-specific antigen (PSA) levels above 10 ng/mL. Scans obtained using the two modalities were interpreted separately. Clinical and biochemical follow-up, radiological studies and biopsies served as benchmarks for the assessments. The impact of PSA level on WBS and SPECT results was also evaluated. The patient-based sensitivity, specificity, accuracy, PPV and NPV values of SPECT examinations were higher than those of WBS, especially in patients with serum PSA levels <40 ng/mL. Multi-FOV SPECT proved to be more sensitive and specific than WBS in detecting bone metastases in PCa patients.

Osteoprotegerin in Serum as a Novel Marker of Bone Metastatic Spread in Prostate Cancer

Prostate cancer (PCa) is the most frequent carcinoma in men and is often complicated by skeletal metastasis (1). Because bone scintigraphy, the standard method of monitoring metastatic bone involvement, is expensive, lacks specificity, and is not particularly suitable for the follow-up of patients, various metabolic bone markers have been studied as indicators for bone metastasis in PCa patients (2)(3). Markers that reflect osteoblast proliferation, e.g., skeletal alkaline phosphatase (sALP), are reportedly useful, which is consistent with the osteoblastic reactions seen in the skeletal metastases (4). The balance between osteoblastic and osteoclastic activity in bone is essentially influenced by osteoclastogenesis. The latter is regulated by three proteins: receptor activator of nuclear factor-κB (RANK), which is expressed on osteoclast precursor cells; its ligand (RANKL), which is expressed on the surface of preosteoblastic and stromal cells; and osteoprotegerin (5)(6). The interaction of RANKL with RANK stimulates the differentiation of osteoclasts, whereas osteoprotegerin blocks this process by functioning as a decoy receptor for RANKL. This novel cytokine system appears to play an important role in the establishment of bone metastases in PCa patients (7). Osteoprotegerin has recently been found to be overexpressed in bone metastases of these patients (8). This overexpression could indirectly favor osteoblastic reactions by inhibiting osteoclastogenesis and might explain the bone lesions typically seen PCa patients. Because tissue overexpression of proteins often is reflected in blood, osteoprotegerin could be a potential serum marker for diagnosis of bone metastasis. Using a recently introduced novel osteoprotegerin assay, we performed the present study to evaluate the diagnostic validity of osteoprotegerin as a potential bone metastasis marker in PCa in comparison with sALP and cross-linked N-telopeptides of type I collagen (NTx), which represent osteoblastic and osteoclastic markers, respectively. The study included 36 male controls (mean age, 51.4 years) with no …