Aspects Of Prostate Cancer Research Articles

PLK1 Phosphorylates WRN at Replication Forks

Prostate cancer, particularly castration-resistant prostate cancer, remains a serious public health issue. Androgen signaling inhibitors have emerged as a major treatment approach, but with limited success. Thus, identification of novel treatment targets is of high clinical relevance. Polo-like kinase 1 (PLK1) has documented roles in various aspects of prostate cancer, including resistance to androgen inhibitors. Radiotherapy is another major approach for treating prostate cancer, but how Plk1 might regulate the efficacy of radiotherapy is unknown. Non-homologous end joining (NHEJ) and homologous recombination (HR) are two major DNA repair pathways, with cellular choices between NHEJ and HR being elegantly regulated by end-processing. However, how the long-range DNA end resection is regulated remains poorly understood. It has been documented that WRN is actively involved in long-range resection pathway. In this study, we demonstrate that PLK1-associated phosphorylation of WRN regulates end resection at double-strand breaks (DSBs), thereby promoting HR and chromosome stability. Cells expressing the WRN unphosphorylatabe mutant show the phenotype similar to WRN null cells, as they lack the ability for long-range resection and increase NHEJ. In summary, we reveal that PLK1-associated MRN phosphorylation promotes end resection, eventually affecting cellular choices for DSB repair pathways.

Controversies in prostate cancer management: Consensus recommendations from experts in northern Spain

In recent years, various aspects of prostate cancer (PC) management have undergone significant changes, including the implementation of therapeutic strategies such as the use of new hormonal agents like abiraterone, apalutamide, enzalutamide or darolutamide and the incorporation of next generation imaging techniques (NGI). However, the evidence regarding the role of NGI and the therapeutic decision-making based on their findings is not solid. Following the methodology of the Advanced Prostate Cancer Consensus Conference (APCCC), a multidisciplinary expert consensus was developed to address controversial questions concerning the use of NGI and clinical management in four priority scenarios: localized PC, PC after radical prostatectomy, PC after radiotherapy with curative intent, and metastatic hormone-sensitive PC. This consensus represents the opinions of medical oncology, radiation oncology and urology physicians and provides useful recommendations for clinical practice.

Controversias en el abordaje del cáncer de próstata: consenso de recomendaciones de expertos del norte de España

In recent years, various aspects of prostate cancer (PC) management have undergone significant changes, including the implementation of therapeutic strategies such as the use of new hormonal agents like abiraterone, apalutamide, enzalutamide or darolutamide and the incorporation of next generation imaging techniques. However, the evidence regarding the role of next generation imaging techniques and the therapeutic decision-making based on their findings is not solid. Following the methodology of the Advanced Prostate Cancer Consensus Conference, a multidisciplinary expert consensus was developed to address controversial questions concerning the use of next generation imaging techniques and clinical management in 4 priority scenarios: localized PC, PC after radical prostatectomy, PC after radiotherapy with curative intent, and metastatic hormone-sensitive PC. This consensus represents the opinions of medical oncology, radiation oncology and urology physicians, and provides useful recommendations for clinical practice.

Histological patterns, subtypes and aspects of prostate cancer: different aspects, different outcomes.

The most common prostatic cancers (PCa) are acinary adenocarcinomas. Histological subtypes have been variably defined. The purpose of this review is to discuss unusual histological patterns and subtypes of acinar adenocarcinoma, as well as other types of PCa and their prognostic and therapeutic relevance. The new term 'subtype' for morphologically defined tumor entities replaced the term 'variant' in the new 2022 classification of the WHO to allow for clear terminological distinction from genetic variants. The 2022 WHO classification mentions prostatic intraepithelial neoplasia (PIN)-like carcinoma, signet-cell-like adenocarcinoma, sarcomatoid carcinoma and pleomorphic-giant-cell adenocarcinoma of the prostate as true subtypes of acinary PCa. Other forms of acinary PCa are termed unusual histological patterns and include atrophic, foamy-cell, microcystic, pseudohyperplastic and mucinous patterns. Nonacinar forms of prostate cancer include other glandular PCa, the ductal adenocarcinoma and the treatment-associated neuroendocrine carcinoma, and nonglandular PCa, the adenosquamous carcinoma, the squamous cell carcinoma and the adenoid cystic (basal cell) carcinoma of the prostate. True subtypes of acinary PCa and other forms of glandular and nonglandular PCa show relevant differences in prognosis and treatment approach compared with classic acinary PCa. The relevance of unusual histological patterns mainly lies in their deceptive benign appearance and the need for pathologists to know about these entities for accurate and timely diagnosis.

Prostate cancer management at an Italian tertiary referral center: does multidisciplinary team meeting influence diagnostic and therapeutic decision-making process? A snapshot of the everyday clinical practice.

Multidisciplinary team (MDT) management decision-making process appears as an interesting tool to answer most aspects of prostate cancer (PCa) diagnosis and treatment, allowing a fairer choice of therapies. The aim of this study to prospectively investigate the impact on prostate cancer clinical management of the uro-oncology MDT meeting at an Italian tertiary referral center. All cases discussed over an 18-months period at San Luigi Hospital uro-oncology MDT were prospectively evaluated for the impact of the MDT discussion on PCa clinical decision-making. Dilemma and management plan in the monodisciplinary visit before and/or after primary treatment were recorded. Subsequently, the MDT discussed the case and reached a consensus decision, which was also recorded. Changes in diagnostic assessment and patient management from pre- to post-MDT meeting were evaluated by a consultant urologist. Overall, 201 patients, of which 99, 81 and 21 with local, advanced and metastatic disease respectively, were selected for MDT evaluation. The most frequent reasons for MDT approach after either PCa diagnosis or primary treatment were metastatic disease or locally advanced disease/positive surgical margins/biochemical recurrence, respectively. Patients with local, advanced and metastatic disease had a significative change of diagnostic/therapeutic management in 23.2%, 46.9% and 33.4%, respectively (P<0.001). Multimodal treatment was recommended in 25.3%. The uro-oncology MDT meeting alters management plans in at least one-quarter of patients reaching almost 50% of cases in locally advanced disease.

Predictability and identifiability assessment of models for prostate cancer under androgen suppression therapy.

The past two decades have seen the development of numerous mathematical models to study various aspects of prostate cancer in clinical settings. These models often contain large sets of parameters and rely on limited data sets for validation. The quantitative analysis of the dynamics of prostate cancer under treatment may be hindered by the lack of identifiability of the parameters from the available data, which limits the predictive ability of the model. Using three ordinary differential equation models as case studies, we carry out a numerical investigation of the identifiability and uncer- tainty quantification of the model parameters. In most cases, the parameters are not identifiable from time series of prostate-specific antigen, which is used as a clinical proxy for tumor progression. It may not be possible to define a finite confidence bound on an unidentifiable parameter, and the relative uncertainties in even identifiable parameters may be large in some cases. The Fisher information ma- trix may be used to determine identifiable parameter subsets for a given model. The use of biological constraints and additional types of measurements, should they become available, may reduce these uncertainties. Ensemble Kalman filtering may provide clinically useful, short-term predictions of pa- tient outcomes from imperfect models, though care must be taken when estimating "patient-specific" parameters. Our results demonstrate the importance of parameter identifiability in the validation and predictive ability of mathematical models of prostate tumor treatment. Observing-system simulation experiments, widely used in meteorology, may prove useful in the development of biomathematical models intended for future clinical application.

The long non-coding RNA PCSEAT exhibits an oncogenic property in prostate cancer and functions as a competing endogenous RNA that associates with EZH2

Prostate cancer (PCa) is the most common malignancy and the leading cause of cancer deaths in males. Recent studies demonstrate that long non-coding RNAs (lncRNAs) are involved in many aspects of PCa. However, their biological roles in PCa remain imperfectly understood. Here,wecharacterized anlncRNA, PCaspecific expression and EZH2-associatedtranscript (PCSEAT, annotated as PRCAT38), which is specifically overexpressedin PCa. We further demonstrated that knockdown of PCSEAT results in the reduction of PCa cell growth and motility, and overexpression of PCSEAT reverses these phenotypes. Furthermore, bioactive PCSEAT is incorporated into exosomes and transmitted to adjacent cells, thus promoting cell proliferation and motility. Mechanistically, we found that PCSEAT promotes cell proliferation, at least in part by affecting miR-143-3p- and miR-24-2-5p-mediated regulation of EZH2, suggesting that PCSEAT and EZH2 competitively ‘sponge’ miR-143-3p and miR-24-2-5p.Overall, ourresultsrevealthat PCSEAT is specifically overexpressed in PCa patients and a potential oncogene in PCa cells via mediating EZH2 activity, indicating that PCSEAT may be a potential therapeutic target in PCa.

Prostate Cancer Information Available in Health-Care Provider Offices: An Analysis of Content, Readability, and Cultural Sensitivity.

Prostate cancer (PrCA) is the most common cancer affecting men in the United States, and African American men have the highest incidence among men in the United States. Little is known about the PrCA-related educational materials being provided to patients in health-care settings. Content, readability, and cultural sensitivity of materials available in providers’ practices in South Carolina were examined. A total of 44 educational materials about PrCA and associated sexual dysfunction was collected from 16 general and specialty practices. The content of the materials was coded, and cultural sensitivity was assessed using the Cultural Sensitivity Assessment Tool. Flesch Reading Ease, Flesch-Kincaid Grade Level, and the Simple Measure of Gobbledygook were used to assess readability. Communication with health-care providers (52.3%), side effects of PrCA treatment (40.9%), sexual dysfunction and its treatment (38.6%), and treatment options (34.1%) were frequently presented. All materials had acceptable cultural sensitivity scores; however, 2.3% and 15.9% of materials demonstrated unacceptable cultural sensitivity regarding format and visual messages, respectively. Readability of the materials varied. More than half of the materials were written above a high-school reading level. PrCA-related materials available in health-care practices may not meet patients’ needs regarding content, cultural sensitivity, and readability. A wide range of educational materials that address various aspects of PrCA, including treatment options and side effects, should be presented in plain language and be culturally sensitive.

Applications of Nanoparticles Probes for Prostate Cancer Imaging and Therapy.

Prostate cancer (PCa) is the most common type of cancer in men with high morbidity and mortality. However, the current treatment with drugs often leads to chemotherapy resistance. It is known that the multi-disciplines research on molecular imaging is very helpful for early diagnosing, staging, restaging and precise treatment of PCa. In the past decades, the tumor-specific targeted drugs were developed for the clinic to treat prostate cancer. Among them, the emerging nanotechnology has brought about many exciting novel diagnosis and treatments systems for PCa. Nanotechnology can greatly enhance the treatment activity of PCa and provide novel theranostics platform by utilizing the unique physical/chemical properties, targeting strategy, or by loading with imaging/therapeutic agents. Herein, this chapter focuses on state-of-art advances in imaging and diagnosing PCa with nanomaterials and highlights the approaches used for functionalization of the targeted biomolecules, and in the treatment for various aspects of PCa with multifunctional nanoparticles, nanoplatforms and nanodelivery system.

Abstract C85: Do African-American veterans need distinct “Prostate Cancer Screening Guidelines” to overcome outcome disparities?

Abstract Background: The United States Preventive Task Force recommended against the prostate-specific antigen (PSA)-based screening for prostate cancer in 2012, a recommendation that applies to all American men. African-American men, however, have the highest incidence of prostate cancer and are more likely to be diagnosed with an advanced stage and poor prognostic-form of prostate cancer. The incidence of prostate cancer is almost 60% higher, and the mortality rate is two- to three-times greater among African Americans than that of Caucasian men1. The Veteran's Health Administration is an unbiased, race-color blind, equal and open access, single-payor, government run health care system2. Yet, due to complex interactions of ethnicity, biology, comorbidities, environmental interactions, as well as social causes, African-American veterans are present with more aggressive disease and carry a worse outcome. Therefore African-American veterans need specific interventions to improve prostate cancer outcomes; i.e., improve survivals and quality of life. We hypothesize that by developing specific and structured prostate cancer screening recommendations, we can improve the overall prostate cancer outcomes among African-American veterans. Methods: We performed a PubMed search using the keywords: African American, African American veterans, Prostate cancer, Outcomes, Molecular markers, Prostate-specific Antigen velocity, and PSA density to derive data relevant to our hypothesis. Results: 1. Men over the age of 65 are most susceptible to prostate cancer, and the average age of veterans is 582. So, they are at a nearly optimal age for preventative prostate cancer screening. 2. The USPSTF guidelines were based on two studies, and one of these studies reported that only 4% of its participants were African American. So, it is inappropriate to use the same guidelines for African American veterans. 3. Several aspects of prostate cancer are different between African Americans and Caucasians. These differences include prostate cancer incidence and outcome, genetic differences, comorbidity, PSA levels, social barriers, and course of the disease. 4. Prior to the new USPSTF guidelines, African American veterans were just as likely as white veterans to undergo PSA testing3. 5. Among the diseases linked to comorbidity with prostate cancer, cardiovascular disease is the most frequent. Hence, the leading cause of death in both the African-American population and the African-American veteran population is cardiovascular disease.2 Conclusion: 1. Because there is no cure for metastatic prostate cancer, early diagnosis and intervention for African-American veterans will lead to saving lives; specific guidelines for prostate cancer will be very beneficial. 2. This will also decrease the costs of treating recurrent and metastatic disease and conserve the resources of the VA Health System. 3. Because the Veterans Health System is equal access, it is an optimal environment to test different prostate cancer screening guidelines for African Americans. 4. Specific draft guidelines will be presented.

Do African-American men need separate prostate cancer screening guidelines?

BackgroundIn 2012, the United States Preventative Services Task Force issued new guidelines recommending that male U.S. residents, irrespective of race, no longer be screened for prostate cancer. In African American men, the incidence of prostate cancer is almost 60 % higher and the mortality rate is two to three times greater than in Caucasians. The purpose of this study is to reduce African American men's prostate cancer burden by demonstrating they need separate screening guidelines.MethodsWe performed a PubMed search using the keywords: African American, Prostate cancer, Outcomes, Molecular markers, Prostate-specific Antigen velocity, PSA density, and to derive data relevant to our hypothesis.ResultsIn our literature review, we identified several aspects of prostate cancer that are different in Caucasian and African American men. These included prostate cancer incidence and outcome, the clinical course of the disease, serum PSA levels, genetic differences, and social barriers. It's also important to note that the USPSTF guidelines were based on two studies, one of which reported that only 4 % of its participants were African American. The other did not report demographic information, but used participants from seven European countries with small African American populations.ConclusionGiven the above, we conclude that separate prostate cancer screening guidelines are greatly necessary to help save the lives of African Americans.

MP39-01 USE OF PSA SCREENING GUIDELINES AMONG PRIMARY CARE PHYSICIANS

You have accessJournal of UrologyProstate Cancer: Detection & Screening V1 Apr 2016MP39-01 USE OF PSA SCREENING GUIDELINES AMONG PRIMARY CARE PHYSICIANS Matt Rosenberg, David Crawford, Jay Newmark, and Mitch Steiner Matt RosenbergMatt Rosenberg More articles by this author , David CrawfordDavid Crawford More articles by this author , Jay NewmarkJay Newmark More articles by this author , and Mitch SteinerMitch Steiner More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.126AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Widespread implementation of prostate specific antigen (PSA) based prostate cancer screening has resulted in the detection of both clinically significant and insignificant cancer. In 2012 the United States Preventive Services Task Force (USPSTF) recommended that screening should not be offered to men unless there was shared decision making. Other guidelines have recommended PSA screening but for only limited circumstances. As 90% of the PSA testing ordered in the United States is by primary care providers (PCP), we sought to determine their opinions about several aspects of prostate cancer and PSA. METHODS A questionnaire was constructed and a pilot evaluation performed at the annual American Academy of Family Practice (AAFP) meeting in the fall of 2015. Participants were chosen randomly for the survey as they visited the exhibit hall. Questions were included to identify demographics, the use of PSA, and impressions of significant values of the laboratory test as well as basic understanding of prostate cancer. RESULTS 153 clinicians were surveyed. 35 (22.9%) respondents stated that they do not recommend PSA based screening. 118 (78.1%) offer PSA screening, with 59 (50%) starting at age 45 and 48 (41%) at age 55. For those that screen, the average age to start was 48.5 years. Respondents referenced several guidelines to support their screening decisions: USPSTF (68), AAFP (30), American Urological Association (AUA) (13), National Comprehensive Cancer Network (NCCN) (1), combination of guidelines (19), their own (3) or none (18). Providers who did not recommend PSA testing referenced USPSTF (19), AAFP (3), AUA (6) or a combination of guidelines (8) to support their decision. When asked what they considered a suspicious PSA level, the responses the providers offered varied from 1.5-12ng/ml, depending on patient age. 149 (97%) respondents believed that some prostate cancers were more lethal than others. 134 (90%) stated they would use a pre-biopsy test to differentiate aggressive from non-aggressive cancers. CONCLUSIONS There are many guidelines available for primary care providers regarding prostate cancer screening. What is apparent is the tremendous confusion and disconnect caused by these messages. It is also apparent that the providers do not want to abandon screening the correct patient. This creates an educational opportunity to help those at the front lines of patient care in regards to management of screening and appropriate pathways for referral. As the specialists in prostate disease, urologists should be the leading these endeavors. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e541 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Matt Rosenberg More articles by this author David Crawford More articles by this author Jay Newmark More articles by this author Mitch Steiner More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Differences in urinary proteins related to surgical margin status after radical prostatectomy.

Presented exploratory pilot study was aimed at evaluation of proteins present in urinary specimens collected from prostate cancer suffering subjects after radical prostatectomy, divided into two experimental cohorts: positive (n=15) and negative (n=15) surgical margins (PSM/NSM). The presence of PSM suggests inadequate cancer clearance and the possible need for additional treatment. Proper identification of these risk-patients is therefore of a paramount importance. Total protein profiles were firstly identified by using SDS-PAGE and compared by using partial least square discrimination analysis (PLS-DA), which revealed differences in molecular weights of 80-99 and 150-235 kDa between the experimental groups. For further identification of proteins, comparative proteomic technologies were employed. Two-dimensional gel electrophoresis with subsequent identification of protein spots by using MALDI-TOF mass fingerprinting revealed differential expression of proteins between NSM/PSM cohorts. Moreover, in PSM group, three uniquely identified proteins (cyclin-dependent kinase 6, galectin-3-binding protein and L-lactate dehydrogenase C chain) were found, which show tight connection with prostate cancer and presence of all of them was previously linked to certain aspects of prostate cancer. These proteins may be associated with the molecular mechanisms of prostate cancer development; hence, their identification may be helpful for the assessment of disease progression risk after radical prostatectomy, but also for possible early diagnosis.

Molecular and Clinicopathological Aspects of Prostate Cancer in Bulgarian Probands.

To correlate the molecular data to the clinicopathological parameters in Bulgarian prostate cancer patients. PCA3 overexpression, TMPRSS2-ERG gene fusion, GSTP1 promoter hypermethylation, somatic mutations in the AR gene and the IVS1-27G > A polymorphism in the KLF6 gene were studied. A total of 148 patients were analyzed: 16 aggressive PCa, 83 non-aggressive PCa, 25 BPH and 24 chronic inflammatory diseases. Real-time RT-PCR, DNA sequencing, and bisulfite conversion of DNA, were applied. All cases with aggressive PCa before treatment were tested positive for PCA3 overexpression, expression of a T2-ERG gene fusion product and GSTP1 promoter hypermethylation. No somatic mutations were detected in the AR gene and all patients showed normal KLF6-IVS1-27G > A genotype. The TMPRSS2-ERG positive status correlates with moderate to poorly differentiated prostate tumors and it is considered as unfavorable disease predictor. Positive GSTP1 promoter hypermethylation seems to be highly specific and the earliest epigenetic change in the prostate gland, which indicates the beginning of the pathological process. The appearance of positive molecular markers in blood was considered as a predictor of PCa dissemination. GSTP1 promoter hypermethylation was found as the earliest and a long-lasting epigenetic marker in blood samples of PCa patients, which makes it suitable as a marker for treatment follow-up. The molecular profile of prostate cancer needs to be strictly monitored during the course of disease treatment, which is of a great help in determining the patient's individual therapy response.

Abstract IA11: The role of bone microenvironment in the lethal progression of prostate cancer

Abstract Lethal prostate cancer (PCa) is clinically characterized by bone-homing and bone- forming metastases, and bone is frequently the initial organ involved in castrate-resistant progression. These clinical observations led investigators to develop bone-tropic radiopharmaceuticals to treat men with advanced PCa. The ability of the bone-homing alpha emitter (RAD-223) to prolong progression free and overall survival establishes the therapeutic relevance of targeting bone 1. The long accepted paradigm of PCa progression has been dominated by the model of evolution from androgen dependence to androgen independence under the selective pressure of castration. Thus, Src family kinases (SFKs) were investigated experimentally and clinically for the treatment of putative “androgen independent” PCa, as SFKs play a role in both tumor growth and bone turnover. The roles of SFKs in migration, invasion, survival of tumor cells, and osteoclast and osteoblast function in tumor microenvironment were supported by numerous clinical and laboratory observations 2, 3. Despite promising phase I /II reports of dasatinib, a multikinase and potent SFK inhibitor, in men with advanced PCa 4, 5, a phase III trial failed to yield the expected survival advantage 6. The result of this trial highlights the difficulties in translating data from cell line models to biologically heterogeneous clinical PCa and in transitioning from phase I/II to phase III clinical trials. The efficacy of dasatinib was not observed likely due to persistent AR signaling, which remains the primary driver of progression in bone by the transition from paracrine to intracrine androgen signaling 7. Based on these considerations, we are testing the efficacy of an androgen biosynthesis inhibitor in combination with dasatinib to better understand the relevance of mechanism(s). A co–clinical investigational strategy is being applied to better define biomarkers to predict clinical efficacy. These studies also highlight the importance of preclinical work that utilizes models that better reflect the heterogeneity of PCa. This problem is partly overcome by patient- derived xenografts (PDX) 8, 9 10. These models reflect many aspects of PCa in bone and can be used to identify therapy targets and better identify both mechanisms of drug efficacy and development of resistance. Studies in PDX have led to identification of FGF signaling as a therapy target 11. Additional studies in PDX implicated the tumor microenvironment in the striking bone responses observed with cabozantinib 13. These observations led us to propose a model of prostate cancer progression founded on the hypothesis that cancer progresses from being an endocrine-driven cancer (Dihydrotestosterone-dependent) to paracrine/intracrine driven (microenvironment-dependent), and then finally to a cell autochthonous phase 12. Continued studies should lead to decisions on therapy treatment that are based on an understanding of markers that predict disease progression. This new paradigm will also result in more effective therapy combinations.

MP53-08 MAGNETIC RESONANCE IMAGING/ULTRASOUND FUSION-GUIDED BIOPSY FOR RE-TARGETING OF ATYPICAL SMALL ACINAR PROLIFERATION

INTRODUCTION AND OBJECTIVES: To overcome the wellknown prostate-specific antigen limits, several new biomarkers have been proposed. Since its introduction in clinical practice, the urinary prostate cancer gene 3 (PCA3) assay has shown promising results for prostate cancer (PC) detection. Furthermore, multiparametric magnetic resonance imaging (mMRI) has the ability to better describe several aspects of PC. METHODS: A prospective study of 171 patients with negative prostate biopsy findings and a persistent high prostate-specific antigen level was conducted to assess the role of mMRI and PCA3 in identifying PC. All patients underwent the PCA3 test and mMRI before a second transrectal ultrasoundguided prostate biopsy. The accuracy and reliability of PCA3 (3 different cutoff points) and mMRI were evaluated. Four multivariate logistic regression models were analyzed, in terms of discrimination and the cost benefit, to assess the clinical role of PCA3 and mMRI in predicting the biopsy outcome. A decision curve analysis was also plotted. RESULTS: Repeated transrectal ultrasound-guided biopsy identified 68 new cases (41.7%) of PC. The sensitivity and specificity of the PCA3 test and mMRI was 68% and 49% and 74% and 90%, respectively. Evaluating the regression models, the best discrimination (area under the curve 0.808) was obtained using the full model (base clinical model plus mMRI and PCA3). The decision curve analysis, to evaluate the cost/benefit ratio, showed good performance in predicting PC with the model that included mMRI and PCA3. CONCLUSIONS: mMRI increased the accuracy and sensitivity of the PCA3 test, and the use of the full model significantly improved the cost/benefit ratio, avoiding unnecessary biopsies. Source of Funding: none

MP53-07 PROSTATE CANCER ANTIGEN 3 (PCA3) AND MULTIPARAMETRIC MAGNETIC RESONANCE (MMRI) IN ASSOCIATION REDUCES UNNECESSARY BIOPSIES: DIGNOSTIC VALUE AND DECISION CURVE ANALYSIS

INTRODUCTION AND OBJECTIVES: To overcome the wellknown prostate-specific antigen limits, several new biomarkers have been proposed. Since its introduction in clinical practice, the urinary prostate cancer gene 3 (PCA3) assay has shown promising results for prostate cancer (PC) detection. Furthermore, multiparametric magnetic resonance imaging (mMRI) has the ability to better describe several aspects of PC. METHODS: A prospective study of 171 patients with negative prostate biopsy findings and a persistent high prostate-specific antigen level was conducted to assess the role of mMRI and PCA3 in identifying PC. All patients underwent the PCA3 test and mMRI before a second transrectal ultrasoundguided prostate biopsy. The accuracy and reliability of PCA3 (3 different cutoff points) and mMRI were evaluated. Four multivariate logistic regression models were analyzed, in terms of discrimination and the cost benefit, to assess the clinical role of PCA3 and mMRI in predicting the biopsy outcome. A decision curve analysis was also plotted. RESULTS: Repeated transrectal ultrasound-guided biopsy identified 68 new cases (41.7%) of PC. The sensitivity and specificity of the PCA3 test and mMRI was 68% and 49% and 74% and 90%, respectively. Evaluating the regression models, the best discrimination (area under the curve 0.808) was obtained using the full model (base clinical model plus mMRI and PCA3). The decision curve analysis, to evaluate the cost/benefit ratio, showed good performance in predicting PC with the model that included mMRI and PCA3. CONCLUSIONS: mMRI increased the accuracy and sensitivity of the PCA3 test, and the use of the full model significantly improved the cost/benefit ratio, avoiding unnecessary biopsies. Source of Funding: none

Editorial referring to the paper published in this issue on pp. 256–262 Inflammatory changes and the prostate

Editorial referring to the paper published in this issue on pp. 256–262 Inflammatory changes and the prostate

Engagement of Renin-Angiotensin System in Prostate Cancer

Angiotensin II (Ang-II) plays a role not only as a vasoconstrictor in controlling blood pressure and electrolyte and fluid homeostasis, but also as a mitogenic factor through the Ang-II type-1 (AT1) receptor in cardiovascular cells. Since a low prevalence of cancer in hypertensive patients receiving angiotensin converting enzyme inhibitors has been reported, the molecular mechanisms of the renin-angiotensin system (RAS) in cancer cells have been elucidated. Interestingly, there is increasing evidence that the RAS is implicated in the development of prostate cancer. As previously reported, AT1 receptor blockers (ARBs), a class of antihypertensive agent, have the potential to inhibit the growth of prostate cancer cells and tumors through the AT1 receptor. This review highlights that the RAS plays a potential role in various aspects of prostate cancer, and ARBs could be useful for treatment of prostate cancer or its chemoprevention.

One Size Fits All in Prostate Cancer: A Story Tale Whose Time has Come and Gone

The touchstone to evaluate accurately the aggressiveness and invasiveness of prostate cancer is something of a holy grail in the facet of urologic oncology. Gene expression and sequencing studies have improved our interpretations of the genetic determinants of the disease but are unsuccessful in the establishment of any unified classification to improve the molecular stratification. These questions addressing failure in rational drug design are difficult to answer in the multifaceted and heterogeneous pathogenesis of prostate cancer. In this review, we have developed a roadmap of the "recalcitrant prostate cancer proteome" to recognize the aspects of prostate cancer that may be helpful in effectively translating these findings to the clinic.