Purpose: This study aimed to prospectively analyze the role of magnetic resonance spectroscopy imaging (MRSI) and dynamic-contrast enhancement magnetic resonance (DCEMR) in the detection of prostate tumor foci in patients with persistently elevated prostate-specific antigen levels (in the range of ≥4 ng/mL to <10 ng/mL) and prior negative random trans-rectal ultrasound (TRUS)-guided biopsy.Experimental Design: This was a prospective randomized single-center study. One hundred and eighty eligible cases were included in the study. Patients in group A were submitted to a second random prostate biopsy, whereas patients in group B were submitted to a 1 H-MRSI-DCEMR examination and samples targeted on suspicious areas were associated to the random biopsy.Results: At the second biopsy, a prostate adenocarcinoma histologic diagnosis was found in 22 of 90 cases (24.4%) in group A and in 41 of 90 cases (45.5%) in group B (P = 0.01). On a patient-by-patient basis, MRSI had 92.3% sensitivity, 88.2% specificity, 85.7% positive predictive value (PPV), 93.7% negative predictive value (NPV), and 90% accuracy; DCEMR had 84.6 % sensitivity, 82.3% specificity, 78.5% PPV, 87.5% NPV, and 83.3% accuracy; and the association MRSI plus DCEMR had 92.6% sensitivity, 88.8% specificity, 88.7% PPV, 92.7% NPV, and 90.7% accuracy, for predicting prostate cancer detection.Conclusions: The combination of MRSI and DCEMR showed the potential to guide biopsy to cancer foci in patients with previously negative TRUS biopsy. To avoid a potential bias, represented from having taken more samples in group B (mean of cores, 12.17) than in group A (10 cores), in the future a MRSI/ DCEMR directed biopsy could be prospectively compared with a saturation biopsy procedure. Clin Cancer Res; 16(6); 1875-83. ©2010 AACR.At present, suspicion of prostate adenocarcinoma is mainly based on three tests: digital rectal examination, prostate-specific antigen (PSA), and trans-rectal ultrasound (TRUS), and is confirmed by TRUS-guided biopsies. The latter is recognized by urologists as the first choice in the diagnosis of prostate pathologies (1). All three modern imaging modalities, namely, computer tomography, ultrasonography, and magnetic resonance (MR), have been considered to have limitations in the diagnosis of prostate adenocarcinoma. Recently some studies (2-5) revealed the high diagnostic accuracy of combined proton 1H-magnetic resonance spectroscopic imaging (1H-MRSI) and dynamic contrast-enhanced imaging magnetic resonance (DCEMR) in the management of prostate cancer. The advantage of MRSI is that the spectroscopic analysis provides metabolic information regarding prostatic tissue by displaying the relative concentrations of chemical compounds within contiguous small volumes of interest (voxels). In the prostate the substances analyzed by MRSI are citrate, creatine, and choline. For practical purposes, prostate adenocarcinoma can be distinguished from healthy peripheral zone tissue on the basis of the (choline + creatine)/citrate ratio (5-7). Normal per...

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Prostate is an immune-competent organ normally populated by inflammatory cells. Prostatic inflammation origin can be multi-factorial and there are some emerging evidences on its possible role as a factor involved in prostate cancer (PC) pathogenesis and progression.This review critically analyzes the role of inflammation as a prognostic factor for progression and aggressiveness of PC. We verified the last 10 years literature data on the association between inflammation and PC aggressiveness, or PC response to therapies.Several studies tried to correlate different inflammatory factors with the aggressiveness and metastatization of PC; all data sustain the role of inflammation in PC progression but they also produce confusion to identify a reliable clinical prognostic marker.Data on patients submitted to radical prostatectomy (RP) showed that cases with marked intraprostatic tissue inflammation are associated with higher rate of biochemical progression; systemic inflammation markers appear to have a significant prognostic value.Analyzing data on patients submitted to radiotherapy (RT) emerges a significant association between high neuthrophil to lymphocyte ratio (NLR) and decreased progression free survival and overall survival; also plateled to lymphocyte ratio (PLR) and C-reactive protein (CRP) have been proposed as significant prognostic factors for progression and overall survival.In patients submitted to androgen deprivation therapy (ADT), inflammation may drive castration resistant PC (CRPC) development by activation of STAT3 in PC cells. NLR has been proposed as independent predictor of overall survival in CRPC submitted to chemotherapy.Most of data are focused on markers related to systemic inflammation such as NLR and CRP, more than specifically to chronic prostatic inflammation. The suggestion is that these inflammatory parameters, also if not specific for prostatic inflammation and possibly influenced by several factors other than PC, can integrate with established prognostic factors.

Study Type - Clinical (prospective trial) Level of Evidence 2b What's known on the subject? and What does the study add? In clinical practice, we know that it is necessary to identify new biomarkers that can better detect prostate cancer (PC), at the same time as reducing the number of unnecessary biopsies. Recently, studies have suggested that the most relevant clinical scenario in which the prostate cancer antigen 3 (PCA3) score could be used comprises patients with a previous negative prostate biopsy and persistently elevated PSA levels. At the same time, although multiparametric MRI is not currently used as a first approach for diagnosing PC, it can be useful for directing targeted biopsies, especially in those patients with elevated PSA levels and a previous negative TRUS-guided biopsy. Considering all of these aspects, the present study aimed to evaluate the role of multiparametric MRI as an additional diagnostic tool for improving the accuracy of the urinary PCA3 test in patients with increased PSA levels and a previous negative prostate biopsy. Our hypothesis is that the potential value of the PCA3 test as a biomarker for PC diagnosis could be improved by the use of multiparametric MRI in directing prostate biopsy. In the present study, we show that, in cases with a previous negative biopsy and persistently elevated PSA levels submitted to multiparametric MRI to direct biopsies, the sensitivity of the PCA3 test significantly improved (79% vs 68%). However, further larger randomized studies on this combination using a new biomarker and a new imaging modality for PC diagnosis are expected. OBJECTIVE To evaluate the role of multiparametric magnetic resonance imaging (MRI) as an additional diagnostic tool for improving the accuracy of the urinary prostate cancer antigen 3 (PCA3) test in patients with an increase in prostate-specific antigen (PSA) levels and a previous negative prostate biopsy. PATIENTS AND METHODS The present study comprised a prospective randomized study on patients with a previous negative transrectal ultrasonography (TRUS)-guided prostate biopsy and elevated PSA levels. In total, 180 cases were analyzed, and all were submitted to PCA3 assay. Patients in group A were submitted to a second random TRUS-guided prostate biopsy, whereas patients in group B were submitted to a multiparametric MRI examination and then to a second TRUS-guided prostate biopsy. RESULTS At the second biopsy, a histological diagnosis of prostate cancer was found in 26 of 84 cases (30.9%) in group A and in 29 of 84 cases (34.5%) in group B. In group A, the sensitivity and specificity of the PCA3 score were 68.0% and 74.5% respectively (positive predictive value of 53.1%, negative predictive value of 84.6% and accuracy of 72.6%). In group B, the sensitivity and specificity of the PCA3 score were 79.3% and 72.7%, respectively (positive predictive value of 60.5%, negative predictive value of 86.9% and accuracy of 75.0%). For the PCA3 score, the area under the receiver-operator characteristic curve was 0.825 (95% confidence...

In cancer patients, the immune system is often altered with an excess of inhibitory factors, such as immunosuppressive cytokines, produced by regulatory T cells (Treg) or myeloid-derived suppressor cells (MDSC). The manipulation of the immune system has emerged as one of new promising therapies for cancer treatment, and also represents an attractive strategy to control prostate cancer (PCa). Therapeutic cancer vaccines and immune checkpoint inhibitors have been the most investigated in clinical trials. Many trials are ongoing to define the effects of immune therapy with established treatments: androgen deprivation therapy (ADT) and chemotherapy (CT) or radiotherapy (RT). This article discusses some of these approaches in the context of future treatments for PCa.

Our aim was to systematically evaluate the benefits of degarelix as antagonist versus agonists of gonadotropin-releasing hormones (GnRH) for the treatment of advanced prostate cancer (PC). This comparison was performed either in terms of biochemical or oncological or safety profiles. To this end we, carried out a systematic review and meta-analysis of the literature.We selected only studies directly and prospectively analyzing the two treatments in the same population (randomized phase III studies). We followed the Preferred Reporting Items for Systematic Reviews and meta-analyses process for reporting studies.After we eliminated studies according to the exclusion criteria, 9 publications were considered relevant to this review. These articles described 5 clinical trials that were eligible for inclusion. The follow-up duration in all trials did not exceed 364 days. This meta-analysis and review comprised a total of 1719 men, 1061 randomized to degarelix versus 658 to GnRH agonists treatment for advanced PC. Oncological results were evaluated only in 1 trial (CS21:408 cases) and they were not the primary endpoints of the study. Treatment emerging adverse events were reported in 61.4% and 58.8% of patients in the degarelix and GnRH agonists group, respectively (odds ratio, OR = 1.17; 95% confidence interval, 95% CI: 0.78–1.77, P > 0.1). Treatment related severe cardiovascular side effects were reported (trial CS21-30-35) in 1.6% and 3.6% of patients in the degarelix and GnRH agonists group, respectively (OR = 0.55, 95% CI: 0.26–1.14, P > 0.1).Our analysis evidences relevant limitations in particular for the comparative evaluation of the efficacy and the oncological results related to degarelix.

Background: androgen receptor variant 7 (AR-V7) has been suggested as potential marker for treatment selection in men with metastatic castration-resistant prostate cancer (mCRPC). The aim of the present review is to critically analyze: frequency of the AR-V7 expression in mCRPC cases—impact of AR-V7 expression on abiraterone, enzalutamide, and taxane therapy. Methods: we searched in the Medline and Cochrane Library database from the literature of the past 10 years. We critically evaluated the level of evidence according to the European Association of Urology (EAU) guidelines. Results: 12 clinical trials were selected. The determination of AR-V7 in peripheral blood using circulating tumor cells mRNA seems to be the preferred method. At baseline, the mean percentage of cases with AR-V7 positivity was 18.3% (range 17.8%–28.8%). All data on mCRPC submitted to enzalutamide or abiraterone reported a significantly ( P <.05) lower clinical progression-free survival (CPFS) and overall survival (OS) in AR-V7+ than AR-V7− cases (CPFS hazard ratio [HR]: 2.3; 95% CI 1.1–4.9; OS HR: 3.0; 95% CI 1.4–6.3). In mCRPC cases submitted to chemotherapies data are not homogeneous and some studies showed no association between CPFS or OS and AR-V7 status (OS HR 1.6; 95% CI 0.6–4.4; P = .40). Conclusions: the suggestion is that taxane therapy is more efficacious than abiraterone or enzalutamide for men with AR-V7+ CRPC. On the contrary, clinical outcomes did not seem to differ significantly on the basis of the type of therapy used among AR-V7− cases.

Introduction To obtain the best results with radical prostatectomy, either from an oncological or a functional point of view, a correct selection of cases and planning of surgery are crucial. Multiparametric magnetic resonance imaging (MRI) promises to make it a successful imaging tool for improving many aspects of prostate cancer management. Aim The aim of this study is to evaluate whether a modern multiparametric MRI can help either to better select prostate cancer cases for a nerve-sparing radical prostatectomy or to improve the functional evaluation related to neurovascular bundles preservation. Main Outcome Measures The effect of preoperative MRI on neurovascular bundle management was examined for the frequency and the appropriateness of changes of the surgical plane on the basis of MRI indications. Methods In a prospective study, 125 consecutive patients with biopsy proven prostate cancer who were scheduled to undergo bilateral nerve-sparing surgery. All patients included into the study were submitted to a preoperative multiparametric MRI. On the basis of MRI evaluation, patients were divided into two groups. Patients in group A were then submitted to a bilateral nerve-sparing (NS) radical prostatectomy (RP), whereas patients in group B were submitted to unilateral NS or non-NS RP. Results In group A, the confirmation from the MRI study to perform a bilateral NS procedure was appropriate in 70 of 73 cases (95.9%), whereas in group B, the surgical plan was appropriate in 28 of 32 cases (87.5%). On the contrary, MRI findings suggested a change in the initial surgical plan (group B) for 32 of 105 cases (30.5%). Of these 32 cases in group B, MRI suggested to perform a unilateral NS procedure in 21 of 32 cases (65.6%) and a non-NS procedure in 11 of 32 cases (34.4%). Conclusions Multiparametric MRI analysis can significantly improve the standard selection and management of prostate carcinoma cases considered for an NS RP.