Mortality In Prostate Cancer Patients Research Articles

KAT5 Negatively regulates the proliferation of prostate cancer LNCaP cells via the caspase 3-dependent apoptosis pathway

ABSTRACTProstate cancer is one of the most common cancers in men over the age of sixty. Lysine acetyltransferase 5 (KAT5) is a histone acetyltransferase involved in transcriptional regulation, DNA repair, and cell signaling pathways. Previous studies have shown that KAT5 expression is reduced in the cytoplasm of the prostate cancer cell line LNCaP when exposed to androgen. Moreover, KAT5 has been reported to have a role in the molecular pathway leading to androgen-independent prostate cancer after long-term androgen deprivation therapy. Here, we showed that KAT5 expression was significantly reduced in prostate cancer tissues and cell lines by using the public databases Oncomine and Human Protein Atlas. Reduced KAT5 expression was significantly associated with high mortality in prostate cancer patients. Furthermore, KAT5 overexpression increased the level of apoptotic markers, such as cleaved-caspase 3, in LNCaP cells, thus enhancing the apoptotic death of LNCaP cells. Taken together, KAT5 induced apoptosis in prostate cancer cells via the caspase-3 pathway, indicating that KAT5 could be a gene therapy target for prostate cancer.

<i>Helicobacter pylori</i> Infection and the Risk of Mortality in Prostate Cancer Patients Receiving Androgen Deprivation Therapy: A Real-World Evidence Study

Background: Helicobacter pylori (H. pylori) is a major risk factor for gastric cancer and may affect androgen activity in men. The association between H. pylori and androgen deprivation therapy (ADT) in patients with prostate cancer (PCa) remain unclear. Methods: This retrospective cohort study linked National Health Insurance (NHI) data to Taiwan Cancer Registry (TCR) and Taiwan Death Registry (TDR) between 1995 and 2016. PCa patients who received ADT were classified into H. pylori infection and non-H. pylori infection groups. The outcomes were overall mortality, prostate cancer-specific mortality, and castration-resistant prostate cancer (CRPC). Propensity score matching was adopted for the primary analysis, and inverse probability of treatment weighting (IPTW) was used for the sensitivity analysis. Findings: Of the 62,014 selected PCa patients, 23,701 received ADT, of whom 3,516 had H. pylori infections and 20,185 did not. After matching, there were 3,022 patients in the H. pylori infection group and 6,044 patients in the non-H. pylori infection group. The mean follow-up period for the matched cohort was 4.8 years. Compared to the non-H. pylori group, the H. pylori group was significantly associated with decreased risks of all-cause mortality (hazard ratio [HR] 0.90; 95% confidence interval [CI] 0.84-0.96) and prostate cancer-specific mortality (HR 0.88; 95% CI 0.81-0.95) in the matched analysis. Interpretation: H. pylori infection was associated with a reduced risk of mortality in PCa patients receiving ADT. Funding: Taoyuan General Hospital, Ministry of Health and Welfare and the Ministry of Science and Technology Taiwan. Declaration of Interest: All authors declared no conflict of interest disclosures. Ethical Approval: This study was approved by the Institutional Review Board of the Tri-Service General Hospital (approval number: TSGHIRB No B-107-04).

BMI1 Drives Metastasis of Prostate Cancer in Caucasian and African-American Men and Is A Potential Therapeutic Target: Hypothesis Tested in Race-specific Models

Metastasis is the major cause of mortality in prostate cancer patients. Factors such as genetic makeup and race play critical role in the outcome of therapies. This study was conducted to investigate the relevance of BMI1 in metastatic prostate cancer disease in Caucasian and African-Americans. We employed race-specific prostate cancer models, clinical specimens, clinical data mining, gene-microarray, transcription-reporter assay, chromatin-immunoprecipitation (ChIP), IHC, transgenic-(tgfl/fl) zebrafish, and mouse metastasis models. BMI1 expression was observed to be elevated in metastatic tumors (lymph nodes, lungs, bones, liver) of Caucasian and African-American prostate cancer patients. The comparative analysis of stage III/IV tumors showed an increased BMI1 expression in African-Americans than Caucasians. TCGA and NIH/GEO clinical data corroborated to our findings. We show that BMI1 expression (i) positively correlates to metastatic (MYC, VEGF, cyclin D1) and (ii) negative correlates to tumor suppressor (INKF4A/p16, PTEN) levels in tumors. The correlation was prominent in African-American tumors. We show that BMI1 regulates the transcriptional activation of MYC, VEGF, INKF4A/p16, and PTEN. We show the effect of pharmacological inhibition of BMI1 on the metastatic genome and invasiveness of tumor cells. Next, we show the anti-metastatic efficacy of BMI1-inhibitor in transgenic zebrafish and mouse metastasis models. Docetaxel as monotherapy has poor outcome on the growth of metastatic tumors. BMI1 inhibitor as an adjuvant improved the taxane therapy in race-based in vitro and in vivo models. BMI1, a major driver of metastasis, represents a promising therapeutic target for treating advanced prostate cancer in patients (including those belonging to high-risk group).

Circulating vitamin D level and mortality in prostate cancer patients: a dose-response meta-analysis.

Previous studies investigating the association of circulating 25-hydroxyvitamin D level with prognosis of prostate cancer yielded controversial results. We conducted a dose–response meta-analysis to elucidate the relationship. PubMed and EMBASE were searched for eligible studies up to July 15, 2018. We performed a dose–response meta-analysis using random-effect model to calculate the summary hazard ratio (HR) and 95% CI of mortality in patients with prostate cancer. Seven eligible cohort studies with 7808 participants were included. The results indicated that higher vitamin D level could reduce the risk of death among prostate cancer patients. The summary HR of prostate cancer-specific mortality correlated with an increment of every 20 nmol/L in circulating vitamin D level was 0.91, with 95% CI 0.87–0.97, P = 0.002. The HR for all-cause mortality with the increase of 20 nmol/L vitamin D was 0.91 (95% CI: 0.84–0.98, P = 0.01). Sensitivity analysis suggested the pooled HRs were stable and not obviously changed by any single study. No evidence of publications bias was observed. This meta-analysis suggested that higher 25-hydroxyvitamin D level was associated with a reduction of mortality in prostate cancer patients and vitamin D is an important protective factor in the progression and prognosis of prostate cancer.

Simvastatin Therapy for Drug Repositioning to Reduce the Risk of Prostate Cancer Mortality in Patients With Hyperlipidemia.

Prostate cancer (PCa) is one of the most commonly diagnosed cancers in the western world, and the mortality rate from PCa in Asia has been increasing recently. Statins are potent inhibitors of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase and are commonly used for treating hyperlipidemia, with beneficial effects for cardiovascular disease and they also exhibit anti-cancer activity. However, the protective effects of statins against PCa are controversial. In this study, we investigated the effect of two types of statins (simvastatin and lovastatin) and the mortality rate of PCa patients by using the Taiwan National Health Insurance Research Database (NHIRD). A total of 15,264 PCa patients with hyperlipidemia records and medical claims from the Registry of Catastrophic Illness were enrolled. The patients were divided into two cohorts based on their statin use before the diagnosis of PCa: statin users (n = 1,827) and non-statin users (n = 1,826). The results showed that patients who used statins exhibited a significantly reduced risk of mortality from PCa [adjusted hazard ratio (HR) = 0.84, 95% CI = 0.73–0.97]. Analysis of the cumulative defined daily dose (DDD) indicated that patients who were prescribed simvastatin ≥ 180 DDD had a dramatically decreased risk of death from PCa (adjusted HR = 0.63; 95% CI = 0.51–0.77). This population-based cohort study demonstrated that statin use significantly decreased the mortality of PCa patients, and that this risk was inversely associated with the cumulative DDD of simvastatin therapy. The results of this study revealed that statins may be used for drug repositioning and in the development of a feasible approach to prevent death from PCa.

Analysis of diagnosis and prognosis of MRP8/14 on prostate cancer

Objective To compare the MRP8/14 level in Normal people, benign prostatic hyperplasia(BPH) patient and prostate cancer patient, and explore the relationgship between MRP8/14 and prostate cancer. Methods 150 cases of normal people, 150 cases of BPH patients and 150 cases of prostate cancer patients were chose from December 2012 to December 2014 in our hospital. ELISA method was used to detect the MRP8/14 level in each group. ROC cure was used to analyse the prediction value of MRP8/14 for prostate cancer. According to the cut off value of MRP8/14, prostate cancer patients were divided into MRP8/14 low value group (MRP8/14<cut off value) and MRP8/14 high value group (MRP8/14≥cut off value), and the difference of patient's clinical characteristics and survival function between high value group and low value group were explored. Results The MRP8/14 level of normal people was (966.7±152.8)ng/ml, while the BPH patient was (1 207.0±190.6)ng/ml, and the prostate cancer patient was (2 833.3±1 101.5)ng/ml, the difference is statistically significant. ROC analysis resμlt showed that the AUC for the prediction of prostate cancer was 0.887(95%CI 0.841-0.934), with a high statistical significance, indicating that MRP8/14 may possess high prediction value for prostate cancer. In addition, the cut off value was 2 845.682 ng/ml, with the specifity of 76.4% and sensitivity of 85.1%. According to the cut off value of MRP8/14, prostate cancer patients were divided into the low MRP8/14 group ( 2 and tumour stage>Ⅲ were much more in MRP8/14 high value group. PSA level, LDH level, AKP level, CRP level and Alkaline Phosphatase level were also significantly increased in MRP8/14 high value group. Besides, prostate cancer patient with an average follow-up of 2 years, a total of 32 cases of patients died, 12 cases in the MRP8/14 low value group with mortality of 13.6%, 20 cases in MRP8/14 high value group with mortality of 32.3%. Kaplan Meier survival function curve shows 2 years survival rate of patients in high value group was significantly reduced. Cox regression analysis showed that MRP8/14 was possible risk factors associated with mortality, and the independent predictors for all-cause mortality during follow-up. Conclusion MRP8/14 was significantly increased in prostate cancer patients, and it was an independent predictor of 2-year mortality in prostate cancer patients. Key words: Myeloid-related protein 8/14; Prostate cancer; Prognostic; Clinical significance

Lipid degradation promotes prostate cancer cell survival.

Prostate cancer is the most common male cancer and androgen receptor (AR) is the major driver of the disease. Here we show that Enoyl-CoA delta isomerase 2 (ECI2) is a novel AR-target that promotes prostate cancer cell survival. Increased ECI2 expression predicts mortality in prostate cancer patients (p = 0.0086). ECI2 encodes for an enzyme involved in lipid metabolism, and we use multiple metabolite profiling platforms and RNA-seq to show that inhibition of ECI2 expression leads to decreased glucose utilization, accumulation of fatty acids and down-regulation of cell cycle related genes. In normal cells, decrease in fatty acid degradation is compensated by increased consumption of glucose, and here we demonstrate that prostate cancer cells are not able to respond to decreased fatty acid degradation. Instead, prostate cancer cells activate incomplete autophagy, which is followed by activation of the cell death response. Finally, we identified a clinically approved compound, perhexiline, which inhibits fatty acid degradation, and replicates the major findings for ECI2 knockdown. This work shows that prostate cancer cells require lipid degradation for survival and identifies a small molecule inhibitor with therapeutic potential.

Predicting survival in node-positive prostate cancer after open, laparoscopic or robotic radical prostatectomy: A competing risk analysis of a multi-institutional database.

To investigate cancer-specific mortality and other-cause mortality in prostate cancer patients with nodal metastases. The study included 411 patients treated with radical prostatectomy and pelvic lymph node dissection for prostate cancer with lymph node metastases at 10 tertiary care centers between 1995 and 2014. Kaplan-Meier analyses were used to assess cancer-specific mortality-free survival rates at 8 years' follow up in the overall population, and after stratifying patients according to clinical and pathological parameters. Uni- and multivariable competing risk Cox regression analyses were used to assess cancer-specific mortality and other-cause mortality. Finally, cumulative-incidence plots were generated for cancer-specific mortality and other-cause mortality after stratifying patients according to the number of positive lymph nodes and the median age at surgery, according to the competing risks method. Men with prostate-specific antigen ≤40 ng/mL and those with one to three positive lymph nodes showed higher cancer-specific mortality-free survival estimates as compared with their counterparts with prostate-specific antigen >40 ng/mL and >3 metastatic lymph nodes, respectively (all P < 0.001). At multivariable Cox regression analyses, preoperative prostate-specific antigen >40 ng/mL, >3 lymph node metastases and pathological Gleason score 8-10 were all independent predictors of cancer-specific mortality (all P-values ≤0.001). On competing risk analysis, when patients were stratified according to the number of positive lymph nodes (namely, ≤3 vs >3), the 8-year cancer-specific mortality rates were 27.4% versus 44.8% for patients aged <65 years, and 15.2% versus 52.6% for patients aged ≥65 years, respectively. Three positive lymph nodes represent the best prognostic cut-off in node-positive prostate cancer patients. In those individuals with >3 positive lymph nodes, the overall mortality rate is completely related to prostate cancer in young patients.

Androgen-deprivation therapy-induced atherosclerosis in prostate cancer: Differences between GnRH-agonist and antagonist

Objectives: Cardiovascular disease (CVD) is one of the most common causes of mortality in prostate cancer patients. In prostate cancer treatment androgen deprivation therapy (ADT) is associated with weight gain and development of the metabolic syndrome. However, different modes of ADT can achieve castration. A post-hoc analysis of phase III trials suggests that GnRH-antagonists are associated with less cardiac events in men with pre-existing CVD during the first year of ADT. We investigated the effects of GnRH-agonist and GnRH-antagonist on the development of CVD in two mouse models.

Association between PSA kinetics and cancer-specific mortality in patients with localised prostate cancer: analysis of the placebo arm of the SPCG-6 study

The prognostic value of prostate-specific antigen (PSA) kinetics in untreated prostate cancer (PCa) patients is debatable. We investigated the association between PSA doubling time (PSAdt), PSA velocity (PSAvel) and PSAvel risk count (PSAvRC) and PCa mortality in a cohort of patients with localised PCa managed on watchful waiting. Patients with clinically localised PCa managed observationally, who were randomised to and remained on placebo for minimum 18 months in the SPCG-6 study, were included. All patients survived at least 2 years and had a minimum of three PSA determinations available. The prognostic value of PSA kinetics was analysed and patients were stratified according to their PSA at consent: ≤10, 10.1-25, and >25 ng/ml. Cumulative incidences of PCa-specific mortality were estimated with the Aalen-Johansen method. Two hundred and sixty-three patients were included of which 116, 76 and 71 had a PSA at consent ≤10, 10.1-25, and >25 ng/ml, respectively. Median follow-up was 13.6 years. For patients with PSA at consent between 10.1 and 25 ng/ml, the 13-year risks of PCa mortality were associated with PSA kinetics: PSAdt ≤3 years: 62.0% versus PSAdt >3 years: 16.3% (Gray's test: P < 0.0001), PSAvel ≥2 ng/ml/year: 48.0% versus PSAvel <2 ng/ml/year: 11.0% (Gray's test: P = 0.0008), and PSAvRC 2: 45.0% versus 0-1: 3.8% (Gray's test: P = 0.001). In contrast, none of the PSA kinetics were significantly associated with changes of 13-year risks of PCa mortality in patients with PSA at consent ≤10 or >25 ng/ml. We found that magnitude changes in 13-year risks of PCa mortality that can be indicated by PSA kinetics depend on PSA level in patients with localised PCa who were managed observationally. Our results question PSA kinetics as surrogate marker for PCa mortality in patients with low and high PSA values. NCT00672282.

546 Patterns of recurrence and long-term cancer-specific mortality of prostate cancer patients treated with salvage radical prostatectomy for radio-recurrent prostate cancer

546 Patterns of recurrence and long-term cancer-specific mortality of prostate cancer patients treated with salvage radical prostatectomy for radio-recurrent prostate cancer

Body mass index and mortality in prostate cancer patients: a dose-response meta-analysis.

Previous studies concerning the association between body mass index (BMI) and mortality in prostate cancer yielded mixed results. We investigated the association by performing a meta-analysis of all available studies. Relevant studies were identified by searching PubMed and EMBASE to August 2015. We calculated the summary hazard ratio (HR) and 95% confidence interval (CI) using random-effects models. We estimated combined HRs associated with defined increments of BMI, using random-effects meta-analysis and dose-response meta-regression models. Thirty-seven cohort studies and one case-control study involving 27 38 000 patients of prostate cancer were selected for meta-analysis. The summary results indicated higher prediagnosis BMI but not postdiagnosis BMI was associated with increased risk of death from prostate cancer. An increment of every 5 kg/m(2) in prediagnosis BMI was associated with a 15% higher prostate cancer-specific mortality (HR=1.15, 95% CI: 1.07-1.23, P<0.01). Prediagnosis or postdiagnosis BMI showed no effect on all-cause mortality in prostate cancer patients. In conclusion, higher prediagnosis BMI is associated with a higher risk of death from prostate cancer. Considering the significant heterogeneity among included studies, these findings require confirmation in future studies.

Cancer Stem-Cell Related miRNAs: Novel Potential Targets for Metastatic Prostate Cancer

Globally Prostate Cancer is the second most commonly diagnosed and sixth leading cause of Cancer mortalities in men worldwide but currently there is no cure for metastatic castration-resistant prostate cancer (CRPC). Chemoresistance and metastasis are the main causes of treatment resistance and mortality in Prostate Cancer patients. Although several advances have been made to control yet there is an urgent need to investigate the mechanisms and pathways for chemoresistance and prostate cancer (PCa) metastasis. Cancer stem cells (CSCs), a sub-population of cancer cells characterised by self-renewal and tumor initiation, have gained intense attention as they not only play a crucial role in cancer relapse but also contribute substantially to chemoresistance. Contributing to the role of CSCs are the miRNAs which are known key regulators of the posttranscriptional regulation of genes involved in a wide array of biological processes including tumorigenesis. The altered expressions of miRNAs have been associated with not only with tumor development but also with invasion, angiogenesis, drug resistance, and metastasis. Thus identification of signature miRNA associated with EMT and CSCs would provide a novel therapeutic strategy for the improvement of current treatment thus leading to increase in patient survival.

Vitamin D and prostate cancer prognosis: a Mendelian randomization study.

Decreased vitamin D levels have been associated with prostate cancer, but it is unclear whether this association is causal. A functional single-nucleotide polymorphism (SNP) in the group-specific component (GC) gene (T > G, rs2282679) has been associated with 25-hydroxy (25-OH) vitamin D and 1.25 dihydroxy (1.25-OH2) vitamin D levels. To examine the hypothesized inverse relationship between vitamin D status and prostate cancer, we studied the association between this SNP and prostate cancer outcome in the prospective PROCAGENE study comprising 702 prostate cancer patients with a median follow-up of 82 months. GC rs2282679 genotypes were not associated with biochemical recurrence [hazard ratios (HR) 0.91, 95 % confidence interval (CI) 0.73-1.12; p = 0.36], development of metastases (HR 1.20, 95 % CI 0.88-1.63; p = 0.25) or overall survival (HR 1.10; 95 % CI 0.84-1.43; p = 0.50). A causal role of vitamin D status, as reflected by GC rs2282679 genotype, in disease progression and mortality in prostate cancer patients is unlikely.

Prostate cancer metastasis: roles of recruitment and reprogramming, cell signal network and three-dimensional growth characteristics.

Prostate cancer (PCa) metastasizes to bone and soft tissues, greatly decreasing quality of life, causing bone pain, skeletal complications, and mortality in PCa patients. While new treatment strategies are being developed, the molecular and cellular basis of PCa metastasis and the “cross-talk” between cancer cells and their microenvironment and crucial cell signaling pathways need to be successfully dissected for intervention. In this review, we introduce a new concept of the mechanism of PCa metastasis, the recruitment and reprogramming of bystander and dormant cells (DCs) by a population of metastasis-initiating cells (MICs). We provide evidence that recruited and reprogrammed DCs gain MICs phenotypes and can subsequently metastasize to bone and soft tissues. We show that MICs can also recruit and reprogram circulating tumor cells (CTCs) and this could contribute to cancer cell evolution and the acquisition of therapeutic resistance. We summarize relevant molecular signaling pathways, including androgen receptors (ARs) and their variants and growth factors (GFs) and cytokines that could contribute to the predilection of PCa for homing to bone and soft tissues. To understand the etiology and the biology of PCa and the effectiveness of therapeutic targeting, we briefly summarize the animal and cell models that have been employed. We also report our experience in the use of three-dimensional (3-D) culture and co-culture models to understand cell signaling networks and the use of these attractive tools to conduct drug screening exercises against already-identified molecular targets. Further research into PCa growth and metastasis will improve our ability to target cancer metastasis more effectively and provide better rationales for personalized oncology.

Aspirin use decreases the risk of prostate cancer recurrence after post-prostatectomy radiotherapy

The objective of the study is to determine if aspirin use is associated with decreased risk of biochemical failure, distant metastasis, and prostate cancer specific mortality in prostate cancer patients after adjuvant or salvage radiation therapy following radical prostatectomy. We identified 189 men with pathologic T2a-4a, N0/X, M0 prostate adenocarcinoma who received adjuvant or salvage radiation therapy following prostatectomy. Aspirin use (defined as use at time of radiation therapy or during follow-up) was present in 60 men (32 %). Cox multivariate analysis was performed using Kaplan-Meier estimation and log-rank test with the following covariates: pre-radiation therapy prostate-specific antigen, Gleason score, prostate-specific antigen doubling time, warfarin or clopidogrel use, aspirin use, surgical margin status, radiation dose, time interval from prostatectomy to radiation therapy, and radiation technique. The median follow-up time was 50 months. Aspirin use was associated with improved 5-year rates of prostate-specific antigen nadir + 2 ng/mL biochemical failure (15 vs. 42 %, p = 0.002), distant metastases (0 vs. 8 %, p = 0.02), and prostate cancer-specific mortality (0 vs. 5 %, p = 0.14). On multivariate analysis, aspirin nonuse (hazard ratio = 2.9, 95 % confidence interval = 1.3–6.6) was the only predictor for prostate-specific antigen nadir + 2 ng/mL biochemical failure. In patients who received adjuvant and salvage radiation therapy after primary radical prostatectomy, aspirin use was associated with a decreased risk of biochemical failure.

Impact of beta-blockers on prostate cancer mortality: a meta-analysis of 16,825 patients.

IntroductionIncreasing evidence suggests that beta-blocker use might be associated with reduced mortality in prostate cancer patients. To provide a quantitative assessment of this association, we pooled data available to examine the association between beta-blocker use and mortality of prostate cancer.MethodsWe identified studies by a literature search of MEDLINE (from 1 January 1966) and EMBASE (from 1 January 1974), through 10 September 2014, and by searching the reference lists of pertinent articles. Two authors independently screened and reviewed the eligibility of each study. The primary outcomes were prostate cancer-specific mortality and all-cause mortality.ResultsA total of four studies including 16,825 patients were included in this meta-analysis. Analysis of all studies showed that beta-blocker use was associated with reduced prostate cancer-specific mortality (hazard ratio =0.85, 95% confidence interval =0.77–0.94), without any heterogeneity between studies (Q=3.59, I 2=16.5%, P=0.309). However, we observed no association with all-cause mortality (hazard ratio =0.97, 95% confidence interval =0.90–1.04). There was also no evidence of the presence of significant heterogeneity between the four studies (Q=2.48, I 2=0.0%, P=0.480).ConclusionThese findings indicate that beta-blocker use was associated with reduced cancer-specific mortality among prostate cancer patients taking beta-blockers.

638 Androgen deprivation therapy and increased non-cancer mortality in prostate cancer patients: Analysis of the number needed to harm

638 Androgen deprivation therapy and increased non-cancer mortality in prostate cancer patients: Analysis of the number needed to harm

Pooled Analysis of C-Reactive Protein Levels and Mortality in Prostate Cancer Patients

IntroductionPrevious studies have reported that higher C-reactive protein (CRP) levels are significantly associated with worse outcome in prostate cancer patients. The size of each individual study was not large enough to allow sufficient statistical power to draw conclusions. We conducted a pooled analysis of individual data of published studies to evaluate the association between increased CRP level and risk of death in prostate cancer, and to find the best CRP cutoff that could predict mortality. Materials and MethodsOriginal research studies on prostate cancer survival and CRP levels were identified (n = 6). Corresponding authors were contacted and invited to share individual data. Two data sets were received (235 patients). The combined hazard ratio (HR) was calculated and adjusted for age, prostate-specific antigen, hemoglobin, and alkaline phosphatase. The best cutoff of CRP was explored using X-title software version 3.6.1. ResultsHigh CRP level was statistically significantly associated with mortality (meta-HR, 1.83 [95% confidence interval (CI), 1.51-2.21]), without evidence of heterogeneity among studies. At pooled analysis, adjusted pooled HR for CRP < 5 versus ≥ 5 mg/L was 1.44 (95% CI, 1.02-20.4). The best CRP cutoff was 12 mg/L: the adjusted HRpooled for CRP < 12 versus ≥ 12 mg/L was 1.53 (95% CI, 1.01-2.32). ConclusionIncreased CRP levels are associated with overall survival in prostate cancer patients. Because CRP is an affordable and readily available assay, it might hold promise in improving prognostication and potentially to predict the activity of specific therapeutic agents.

Cardiovascular events associated with androgen deprivation therapy in patients with prostate cancer: a systematic review and meta-analysis.

A recently published meta-analysis of randomized clinical trials (RCT) showed that androgen deprivation therapy (ADT) did not significantly increase cardiovascular mortality in prostate cancer patients. However, cardiovascular morbidity, which can impact quality of life, was not evaluated. To evaluate the risk of cardiovascular morbidity associated with ADT in patients with prostate cancer. We conducted a literature search from January 1960 to June 2012. RCT and large cohort studies that evaluated first-line endocrine therapy and ADT longer than 6 months were screened for inclusion. In total, 126,898 patients were included in four cohort studies, and 10,760 patients were included in nine RCTs. Analysis of the RCTs showed no differences in the development of acute myocardial infarction (AMI) (OR 1.23; 95 % CI 0.92-1.64; I (2): 0 %) among the patients receiving ADT or not. The analysis of randomized studies that reported other nonfatal cardiovascular events demonstrated a significant increase in such events in the group receiving ADT (OR 1.55; 95 % CI 1.09-2.20; I (2): 0 %). When the large cohort studies were included in the analysis, an increased risk of AMI among men with ADT was found (OR 2.01, 95 % CI 1.90-2.13; I (2): 91,3 %). The use of ADT in prostate cancer patients corresponded with a significant increase in cardiovascular morbidity associated with AMI and with nonfatal events. Therefore, ADT is linked to a significant negative impact on quality of life. Periodic cardiovascular evaluation is required for these patients.