Frequency Of Prostate Cancer Research Articles

MP75-20 HOW THE POLITICAL PARTY THAT HOLDS YOUR ELECTORATE DETERMINES IF YOUR PROSTATECTOMY IS VIA ROBOT OR OPEN SURGERY

You have accessJournal of UrologyCME1 Apr 2023MP75-20 HOW THE POLITICAL PARTY THAT HOLDS YOUR ELECTORATE DETERMINES IF YOUR PROSTATECTOMY IS VIA ROBOT OR OPEN SURGERY Anne Hong, Nathan Papa, Gregory Jack, Cliodhna Browne, and Damien Bolton Anne HongAnne Hong More articles by this author , Nathan PapaNathan Papa More articles by this author , Gregory JackGregory Jack More articles by this author , Cliodhna BrowneCliodhna Browne More articles by this author , and Damien BoltonDamien Bolton More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003349.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In a nationalised health system it would be expected that surgical approach to cancer would be centralised, and that there would be minimal variation within a single city. Anecdotally however there seemed to be areas of our large city where fewer people were being treated by minimally invasive surgery for prostate cancer. We sought to objectify whether there were variations between electorates that were represented in the frequency of prostate cancer being treated by robotic vs open surgery. METHODS: All radical prostatectomies in the city of Melbourne Australia were identified for a 3 year period, coinciding with the electoral cycle for representatives from this state. The percentage of patients from each electorate who had treatment by robotic vs open radical prostatectomy was calculated. Electorates were then compared by the political party which was the incumbent in the seat. RESULTS: Marked variations in the frequency of robotic radical prostatectomy in a given electorate were apparent, with a range from 24% to 79%. Open radical prostatectomy was the inverse. These variations were however consistently in favour of robot assisted surgery in the seats held by the more conservative parties, and in favour of open surgery in those seats more aligned to the parties that aligned with the left of the political spectrum. CONCLUSIONS: Even in a nationalised healthcare system patients from electorates that have voted in a conservative representative are more likely to be treated with minimally invasive surgery than open surgery. Measures should be taken to correct this inequity and to provide the same standard of care to all members of the community regardless of where they live in a metropolitan area. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1088 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Anne Hong More articles by this author Nathan Papa More articles by this author Gregory Jack More articles by this author Cliodhna Browne More articles by this author Damien Bolton More articles by this author Expand All Advertisement PDF downloadLoading ...

Clinical Impact of Liquid Biopsy in Prostatic Cancer: A Literature Review

The most prev amost prev abstract alent solid tumor in men worldwide is prostate cancer. The need for biomarkers to guide management choices is critical given the frequency of prostate cancer and its relatively lengthy clinical course. Based on a patient's unique risk stratification, which considers pathologic characteristics from a prostate biopsy, prostate-specific antigen (PSA) level, imaging, and other patient factors, decisions about localized prostate cancer treatment options, such as active surveillance, surgical excision, or targeted radiation, are made. An attractive method for thorough cancer analysis is to use "liquid biopsies" made up of analytes from a peripheral blood draw. These methods can be used as prognostic and predictive biomarkers as well as ready tissue sources for molecular profiling during the course of a disease and are straightforward, safe, and simple to repeat. Researchers conduct an examination of articles that are in accordance with the issue to be studied. Articles used in literature review are obtained through the database of international journal providers through PubMed, we investigated eleven clinical studies and discussed what happened in these clinical studies and the extent of the effectiveness of liquid biopsy in prostatic cancer, in one study there was relative impact of common circulating tumor DNA alterations on patient response to the most widely used large, randomize advanced prostate cancer. Other studies reported that ZNF660 methylation analysis can potentially help to stratify low-/intermediate-grade PCs into indolent vs. more aggressive subtypes. Another study found that tumor-derived biomarkers in platelets of CRPC patients enabled prediction of the outcome after abiraterone therapy with higher accuracy than baseline serum PSA or PSA response. One study reported that de novo positive CTC count after androgen deprivation therapy is probably due to a passive mechanism associated with the destruction of the tumor. In this review, we suggest that liquid biopsy could be used as biomarker for prostatic cancer, Further studies are needed to enhance liquid biopsy efficacy.

FLG Gene Mutation Up-regulates the Abnormal Tumor Immune Response and Promotes the Progression of Prostate Cancer.

Prostate Cancer (PCa) ranks sixth with regard to the cause of cancerinduced male diseases worldwide, and inflammation is closely associated with its morbidity, deterioration, and prognosis. Tumor Mutation Burden (TMB) is identified to be the most common biomarker for the prediction of immunotherapy. But it is still unclear about the relationship of gene mutations in PCa with TMB and immune response. To study the relationship between gene mutation and anti-tumor immune response in the prostate cancer tumor microenvironment. In the present work, the PCa somatic mutation data were collected from the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) datasets. As a result, 8 genes with high mutation frequency, including TP53, PTEN, TTN, FLG, CTNNB1, SPOP, MUC16, and KMT2C, were discovered to be covered by 4 cohorts from the United States, Canada, the United Kingdom, and China. Overall, the FLG mutation was related to a greater TMB, which predicted the dismal prognostic outcome. Besides, the CIBERSORT algorithm and Gene Set Enrichment Analysis (GSEA) were adopted for analysis, which revealed that FLG mutation remarkably promoted immune response in the context of PCa and accelerated cancer development. To sum up, FLG shows a high mutation frequency in PCa, and is related to the increase in TMB, up-regulation of abnormal immune responses in tumors, and promotion of tumor progression. Therefore, it may be used as a biomarker to predict the abnormal immune responses and provide a therapeutic target for immunotherapy in the treatment of PCa.

Mortalidade por câncer de próstata no estado do Piauí: perfil epidemiológico e tendências

Objetivo: Analisar a frequência do câncer de próstata no Piauí, no período de 2007 a 2016. Métodos: Trata-se de estudo retrospectivo, onde a coleta dos dados ocorreu na base de dados DATASUS (Departamento de Informática do SUS), no Sistema Informação de Mortalidade (SIM), baseado nos dados estatísticos populacional do IBGE 2010 e processados no Microsoft Excel 2010. Os dados estatísticos foram realizados a partir de cálculos de análises de tendência baseados nas variáveis dependentes (y) que foram as taxas por ano de mortalidade e independente (x) considerados os anos de estudo. Resultados: No Piauí, entre os anos de 2007 a 2016 obteve-se cerca de 2281 casos de morte por Câncer de próstata, onde a os idosos com mais de 80 anos, pardos possuem maior prevalência. Conclusão: Tendo esse estudo fortalecido à importância da realização dos testes de prevenção e diagnóstico precoce, além de servido como instrumento de análise dos índices de letalidade por câncer de próstata.

Incidental pulmonary embolism in oncologic patients\u2014a systematic review and meta-analysis

PurposeIncidental pulmonary embolism (IPE) is a common finding on computed tomography (CT). IPE is frequent in oncologic patients undergoing staging CT. The aim of this analysis was to provide the pooled frequency of IPE and frequencies of IPE in different primary tumors.MethodsMEDLINE, SCOPUS, and EMBASE databases were screened for studies investigating frequency of IPE in oncologic staging CT up to February 2020. Overall, 12 studies met the inclusion criteria and were included into the present study.ResultsThe pooled analysis yielded a total of 28,626 patients. IPE was identified in 963 patients (3.36%, 95% CI = 3.15; 3.57). The highest frequency was found in prostate cancer (8.59%, 95%CI = 3.74; 13.44), followed by hepatobiliary carcinoma (6.07%, 95%CI = 3.09; 9.05) and pancreatic cancer (5.65%, 95%CI = 3.54; 7.76). The lowest frequencies were identified in tumors of male reproductive organs (0.79%, 95%CI = 0.21; 1.37) and hematological diseases (1.11% 95%CI = 0.74; 1.48).ConclusionThe overall frequency of IPE in oncologic patients was 3.36%. There are considerable differences in regard to primary tumors with the highest frequency in prostate cancer and pancreatic and hepatobiliary carcinomas.

Abstract A018: Distinct genomic alterations in prostate cancer of African American men

Abstract Background: In recent years remarkable ethnic/racial differences in the frequency of prostate cancer (CaP) driver gene alterations have emerged. Along the lines of ethnic differences in CaP genomes, oncogenic activation of ERG proto-oncogene and deletion of the PTEN tumor suppressor gene are most widely studied. These findings underscore distinct biology of prostate cancer in different ethnicities and races. We have reported the cumulative analyses of 435 patients (whole genome sequencing (WGS): 14, FISH evaluations: 101, SNP array: 320) comparing CaP genomes of African American (AA) and Caucasian American (CA) patients. An AA CaP genome-associated deletion was identified and mapped to the Limbic System-Associated Membrane Protein (LSAMP) gene locus. Further examination of the data indicated the AA CaP-genome associated deletion of the Chromodomain Helicase DNA Binding Protein 1(CHD1) gene. The goal of the current study is the comparative assessment of frequencies and prognostic associations of CaP genome alterations in the context of racial/ethnic differences. Methods: A prostate tumor tissue microarray (TMA) of benign and tumor foci (500+ cores) was generated by sampling 2-3 cores representing the range of cell morphology in matched cohort of 42 AA and 59 CA patients with up to 20 years of follow-up. Comparative evaluation of frequencies and prognostic associations of ERG oncoprotein by immunohistochemistry and the deletion of LSAMP, CHD1, and PTEN genes by FISH was performed. ERG frequencies were further assessed in index tumors of Chinese CaPs (N=100) and were compared to ERG frequencies in index tumors of patients from the United States equal-access military health-care system (N=336 AA and N=594 CA). Results: Higher frequencies of recurrent deletions of CHD1 (29% AA vs. 10% CA p=0.017) and LSAMP (26% AA vs. 7% CA, p=0.006) were identified in AA CaP compared to CA CaPs. These deletions were associated with significantly higher risk of rapid biochemical recurrence. In contrast, PTEN deletions (15% AA vs. 63% CA) and the frequency of ERG positive CaPs (26% AA vs. 64% CA) were more frequent among CA CaPs. Comparative evaluation of ERG frequencies in CaPs (N=1,292) underscores highest ERG frequency among CA patients (49.3%) followed by AA (23.2%) and Chinese (22%) men. Conclusions: In light of distinct biology of CaPs in ethnically/racially diverse CaP patient populations, there is a need for developing broadly applicable diagnostic, prognostic marker panels and therapeutic approaches. Higher frequency of CHD1 deletion in CaPs of AA patients may provide new therapeutic opportunities due to the sensitivity of CHD1 deletion harboring tumors to PARP inhibitors and platinum agents. Acknowledgments: This research was supported by the CPDR-USU program HU0001-10-2-0002, the National Cancer Institute R01CA162383 grant, the EDRN/NCI ACN12011-001-0 grant, the Snyder Medical Foundation, the Otto Mønsteds Foundation, the Mazzone Foundation, the Breast Cancer Research Foundation, the Novo Nordisk Foundation, and grants by MTA-TKI643/2012, KTIA_NAP_13-2014-0021. Citation Format: Albert Dobi, Gyorgy Petrovics, Hua Li, Denise Young, Shyh-Han Tan, Yongmei Chen, Qingyu Xiao, Yidi Sun, Hong Li, Yixue Li, Yuan Ji, Jun Hou, Wendy Wang, Jacob Kagan, Guo-Ping Zhao, Sudhir Srivastava, Reinhard Ebner, Inger L. Rosner, Jennifer Cullen, Matthew Freedman, Isabell Sesterhenn, Zoltan Szallasi, Shiv Srivastava. Distinct genomic alterations in prostate cancer of African American men [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr A018.

Social determinants of prostate cancer in the Caribbean: a systematic review and meta-analysis

BackgroundProstate cancer remains the leading cause of cancer deaths among Caribbean men. However, little data exists on the influence of social factors on prostate cancer in the Caribbean setting. This article supports the 2011 Rio Political Declaration on addressing health inequalities by presenting a systematic review of evidence on the role of social determinants on prostate cancer in Caribbean men. It aims to determine the distribution, by known social determinants of health, of the frequency and adverse outcomes of prostate cancer among Caribbean populations.MethodsObservational studies reporting an association between a social determinant and prostate cancer frequency and outcomes were sought in MEDLINE, EMBASE, SciELO, CINAHL, CUMED, LILACS, and IBECS databases. Fourteen social determinants and 7 prostate cancer endpoints were chosen, providing 98 possible relationship groups exploring the role of social determinants on prostate cancer. Observational studies with > 50 participants conducted in Caribbean territories between 2004 and 2016 were eligible. The review was conducted according to STROBE and PRISMA guidelines. Random-effects meta-analyses were performed.ResultsFrom 843 potentially relevant citations, 13 articles from 9 studies were included. From these included studies, 24 relationships were reported looking at 11 distinct relationship groups, leaving 90 relationship groups (92% of all relationship groups) unexplored. Study heterogeneity and risk of bias restricted results to a narrative synthesis in most instances. Meta-analyses showed more diagnosed prostate cancer among men with less formal education (n = 2 studies, OR 1.60, 95%CI 1.18–2.19) and among men who were married (n = 3 studies, OR 1.54, 95%CI 1.22–1.95).ConclusionsThis review highlights limited evidence for a higher occurrence of diagnosed prostate cancer among Caribbean men with lower levels of education and among men who are married. The role of social determinants on prostate cancer among Caribbean men remains poorly understood. Improvements in study quantity and quality, and reduced variability in outcomes and reporting are needed. This report represents the current evidence, and provides a roadmap to future research priorities for a better understanding of Caribbean prostate cancer inequalities.

The Effect of Shift Work on Urogenital Disease: a Systematic Review.

Non-standard shift work schedules negatively impact the overall health of shift workers, and several studies have shown that shift work, specifically, is detrimental to urogenital health. The aims of this study are to systematically review the literature and determine the effect of shift work on the outcomes of hypogonadism, male infertility, lower urinary tract symptoms, and urogenital cancers. Recent evidence supports associations between non-standard shift work and an increase in the frequency of prostate cancer and the severity of erectile dysfunction, lower urinary tract symptoms, and hypogonadal symptoms, as well as worsening of semen parameters and fertility. These associations are strengthened by the presence of shift work sleep disorder (SWSD) which affects up to 20% of shift workers. No studies have assessed the impact of shift work on the frequency or severity of nephrolithiasis, interstitial cystitis, pelvic pain, prostatitis, or urinary tract infections. Non-standard shift work has been associated with a variety of negative health outcomes and urologic complications, especially with concurrent shift work sleep disorder. Recognition of these elevated risks among shift workers can aid in more effective screening for urologic conditions.

MP87-01 RECURRENT MITOCHONDRIAL DNA MUTATION FOUND IN BONE METASTASES

You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) IV1 Apr 2018MP87-01 RECURRENT MITOCHONDRIAL DNA MUTATION FOUND IN BONE METASTASES Carrie Sun, Colm Morrissey, John Petros, and Rebecca Arnold Carrie SunCarrie Sun More articles by this author , Colm MorrisseyColm Morrissey More articles by this author , John PetrosJohn Petros More articles by this author , and Rebecca ArnoldRebecca Arnold More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2901AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We have previously described a single DNA base alteration in the mitochondrially encoded ND3 gene (A10398G; Thr114Ala) that occurs as a bone metastasis-specific alteration in the majority of 13 prostate cancer patients with bone metastasis (Bone 78 (2015) 81-86). The objective of this study was to define the incidence of this single base alteration in an expanded series of patients and to determine whether the prostate primary also harbored this mutation or if it occurred de-novo in the bone using an ultra-sensitive assay. METHODS We developed a digital drop PCR (ddPCR) fluorescent assay using the RainDance platform designed to quantitatively interrogate the mitochondrial DNA (mtDNA) nucleotide position 10398 missense mutation. Clinical specimens from a rapid autopsy program included 39 patients with multiple tissues available including the prostate primary, soft tissue metastases, bone metastases and normal tissue controls. The number of DNA molecules with the wild type and mutant base were counted and mutation levels compared between normal tissue, primary tumor and metastatic sites. RESULTS Of 39 patients with bone metastasis that were evaluated, 20 (51%) had significantly increased levels of the 10398 missense mutation in the mitochondrially encoded ND3 gene compared to normal uninvolved tissue. The increase ranged from 2.5-59 fold in the bone. On average, 200,000 DNA molecules were counted from each tissue examined. Because of the ultra-sensitive nature of the ddPCR assay used, we also identified the same base alteration in 2 lymph node metastases and one adrenal metastasis. Of the 3 primary prostate tissues examined that gave adequate results, 2 did not have an increased alteration at the 10398 position compared to normal tissue and one did. Of the two prostate primaries without the mutation, neither bone metastasis had the mutation. In the patient whose prostate primary tumor had mutation (2.2=fold increase over normal tissue), the bone metastasis also had the mutation (36-fold increase over normal tissue). CONCLUSIONS In this expanded cohort of 39 patients with prostate cancer bone metastases, the majority (51%) had a substantially increased level of missense mutation at the 10398 nucleotide position of the mitochondrial genome in the bone metastasis. This mutational hot-spot is unprecedented in frequency in prostate cancer and implies a strong selective pressure for bone metastatic cells that had acquired this mutation in the ND3 gene of respiratory complex 1. A smaller number of soft-tissue metastases also demonstrated enrichment of this mutation. While the small number of primary prostate cancers available for analysis preclude any firm conclusions, the two cases without the mutation also did not have the mutation in the bone metastasis while the one with the mutation in the prostate primary demonstrated a 36-fold increase of the mutation in the bone metastasis. It is therefore possible that the mutation arises in the prostate and is selected for in the bone metastasis. This finding that the exact same missense mutation is present in over 50% of patients prostate cancer bone metastases far exceeds any somatic mutation previously reported in prostate cancer suggesting functional importance. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e1187 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Carrie Sun More articles by this author Colm Morrissey More articles by this author John Petros More articles by this author Rebecca Arnold More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Polygamy, sexual behavior in a population under risk for prostate cancer diagnostic: an observational study from the Black Sea Region in Turkey.

ABSTRACTAim:Although prostate cancer (PCa) is the most common cancer type in men, a replaceable risk factor has not yet been established. In our study, we assessed the relationship between the number of sexual partners, age of first sexual experience and age of first masturbation and prostate cancer incidence.Materials and Methods:In Ordu University Department of Urology between January 2013 and September 2016, in PSA elevation and rectal examination, patients with prostate biopsy were evaluated due to nodule palpation in the prostate. At younger ages and at present, their first masturbation ages, first sexual debut ages, and total sexual partner numbers were recorded. The correlation between the obtained data and PCa frequency was evaluated.Results:The study included 146 patients with PCa identified on biopsy and 171 patients with benign biopsy results who answered the questions. 66.7% of the ones whose biopsy results were benign and 40.6% of cancer suspects had only one sexual partner. The median number of sexual partners was 1±4 (1-100) in the benign group and 2±6 (1-500) in the malignant group (p=0.039). There was a negative correlation between age of first sexual debut and number of partners (r: −0,479; p <0.001).Conclusion:In our study, it appears that there may be an association between the number of sexual partners and prostate cancer in the patient group with PSA level above 4ng/mL. Avoidance of sexual promiscuity or participation in protected sex may be beneficial to protect against prostate cancer.

Ethnicity and ERG frequency in prostate cancer.

Emerging observations emphasize a distinct biology of prostate cancer among men of different ethnicities and races, as demonstrated by remarkable differences in the frequency of ERG oncogenic activation, one of the most common and widely studied prostate cancer driver genes. Worldwide assessment of ERG alterations frequencies show consistent trends, with men of European ancestry having the highest rates of alteration and men of African or Asian ancestries having considerably lower alteration rates. However, data must be interpreted cautiously, owing to variations in assay platforms and specimen types, as well as ethnic and geographical classifications. Many opportunities and challenges remain in assessing cancer-associated molecular alterations at a global level, and these need to be addressed in order to realize the true potential of precision medicine for all cancer patients.

All-Cause Mortality for Life Insurance Applicants with a History of Prostate Cancer.

- To determine the all-cause mortality of life insurance applicants diagnosed with prostate cancer currently or at some time in the past. - Prostate cancer is common and a frequent cause of cancer death. Both the frequency of prostate cancer in men and its propensity for causing premature mortality require insurance company medical directors and underwriters to have a good understanding of prostate cancer-related mortality trends, patterns, and outcomes in the insured population. - Life insurance applicants with reported prostate cancer were extracted from data covering United States residents between November 2007 and November 2014. Information about these applicants was matched to the Social Security Death Master (SSDMF) file for deaths occurring from 2007 to 2011 and to another commercially available death source file (Other Death Source, ODS) for deaths occurring from 2007 to 2014 to determine vital status. Actual to Expected (A/E) mortality ratios were calculated using the Society of Actuaries 2015 Valuation Basic Table (2015VBT), select and ultimate table (age last birthday) and the 2013 US population as expected mortality ratios. All expected bases were not smoker distinct. - The study covered applicants between the ages of 45 and 75 and had approximately 405,000 person-years of exposure. Older aged applicants had a lower mortality ratio than those who were younger. Applicants 45 to 54 had the highest mortality ratios in the first year after diagnosis which steadily decreased in years 6 to 10 with an increase in the mortality ratio for those over 10 years from diagnosis. Relative mortality rate was close to unity for those with localized cancer across all age groups. The mortality ratio was 2 to 4 times greater for those with cancer in 1 positive node, and much greater with 3 positive nodes. For each time-from-diagnosis category, the relative mortality ratios compared to age were highest in the 45-54 age group. The A/E mortality ratios based on the 2015VBT were consistently 3 to 4 times that of the mortality ratios based on the 2013 US population. - The mortality patterns of insurance applicants with prostate cancer were similar to that observed in individuals with prostate cancer in the general population. Applicant age, time to diagnosis and cancer severity were the most significant variables to predict mortality.

Radiotherapy cannot prolong overall survival of young prostate cancer patients with bone metastases.

BackgroundPatients with prostate cancer is commonly diagnosed with bone metastases. With the growing use of prostate-specific antigen testing, the frequency of prostate cancer has progressively increased in patients younger than 70 years. Radiotherapy is recognized for its effect on local control of bone metastases, but whether it could prolong overall survival is still controversial.MethodsA total of 113 prostate cancer patients (<70y) with bone metastases were retrospectively analyzed. The Kaplan–Meier method was used for survival analysis with log-rank test. Multivariate analysis was performed to find the prognostic factors with the COX regression model.ResultsThe 1-, 2-, 3-, 5-, 7- and 10-year survival rates were 97.14, 82.86, 62.61, 38.76, 25.83 and 13.84 % respectively in the radiotherapy group, and 92.75, 73.91, 54.66, 36.63, 26.03 and 17.85 % respectively in the non-radiotherapy group, which showed no significant difference. Multivariate COX regression showed the overall survival was associated with alkaline phosphatase when bone metastases occurred and the number of bone metastases.ConclusionWith the advances in life-prolonging treatment of metastatic prostate cancer, radiotherapy may not be the first choice for young bone metastatic prostate cancer patients in order to improve survival.

Incidental Prostate Cancer Frequency and Features of Patients Undergoing Radical Cystoprostatectomy

Incidental Prostate Cancer Frequency and Features of Patients Undergoing Radical Cystoprostatectomy

Prostate cancer detection rates of negative MP-MRIs.

91 Background: Increased lesion suspicion score on MRI is known to be associated with increased grade of prostate cancer. However, the negative predictive value (NPV) of MRI is still being investigated. To determine the NPV of mpMRI, we evaluated the frequency of prostate cancer (CaP) detection by 12-core template mapping biopsy (Mbx) in men whose mpMRI showed no suspicious regions. Methods: 374 men undergoing MRI-US fusion biopsy from 12/2012 to 06/2015 were enrolled in an IRB-approved database and met inclusion criteria for this study. The mpMRI sequences T2-weighted, diffusion-weighted imaging, and dynamic contrast enhancement were used to identify and classify targets as low, medium, and high suspicion. Men with negative mpMRI received a template 12-core template mapping biopsy. Only patients with complete mpMRI sequences were included. Results: 53 men with a negative MRI were identified (mean age=63.5 years, PSA=7.53 ng/mL, mean prostate volume=67.2 mL). The NPV of negative MRI was 64.2% for any cancer and 96.2% for clinically significant cancer (Gleason≥7). Men on active surveillance had the highest CDR 56.3%, compared to 38.9% for biopsy-naive men, and 15.8% for men with prior negative biopsy (Figure 1). Clinically significant CaP was found in two patients: Gleason 4+3 in a patient on Active Surveillance, and 4+4 in a biopsy naïve patient. Conclusions: Negative MRI has a high NPV (96%) for clinically significant CaP found in 12-core template mapping biopsy. If we did not biopsy mpMRI negative men, we would have missed 16 patients with Gleason 6 and 2 patients with ≥ Gleason 7. Clinicians can use this information in patient counseling to discuss the likelihood of detecting significant cancer – though these findings should be reproduced widely before a negative MRI is used to recommend against biopsy. Sources of funding: NIH-National Institute of Diabetes and Digestive and Kidney Diseases [Table: see text]

PREVENTION AND TREATMENT OF ERECTILE DYSFUNCTION IN PATIENTS AFTER RADICAL NERVESPARING PROSTATECTOMY

The purpose of our research is to improve the quality of life of patients undergoing radical prostatectomy. With the increasing frequency of prostate cancer and determining the effectiveness of surgical treatment significantly increased the number of radical prostatectomy. Surgical treatment is definitely in much greater extent when compared to radiation treatments related to the development of impotence, erectile dysfunction and urinary incontinence.The incidence of erectile dysfunction after prostatectomy ranges from 10 to 50%. Therefore, the development of new programmes for the rehabilitation of patients can improve their quality of life, due to the greater likelihood of recovery of erectile function after the operation. In our study we observed 84 patient. The incidence of erectile dysfunction was 76%. After applying one of the existing methods of stimulation: FDE5 inhibitors, intracavernose injections of prostaglandin, physical therapy, we were able to increase the effectiveness of treatment up to 54.8%, 40% and 70% respectively.

Antibody targeting of HER2/HER3 signaling overcomes heregulin-induced resistance to PI3K inhibition in prostate cancer.

Dysregulated expression and/or mutations of the various components of the phosphoinositide 3-kinase (PI3K)/Akt pathway occur with high frequency in prostate cancer and are associated with the development and progression of castration resistant tumors. However, small molecule kinase inhibitors that target this signaling pathway have limited efficacy in inhibiting tumor growth, primarily due to compensatory survival signals through receptor tyrosine kinases (RTKs). Although members of the epidermal growth factor receptor (EGFR), or HER, family of RTKs are strongly implicated in the development and progression of prostate cancer, targeting individual members of this family such as EGFR or HER2 has resulted in limited success in clinical trials. Multiple studies indicate a critical role for HER3 in the development of resistance against both HER-targeted therapies and PI3K/Akt pathway inhibitors. In this study, we found that the growth inhibitory effect of GDC-0941, a class I PI3K inhibitor, is markedly reduced in the presence of heregulin. Interestingly, this effect is more pronounced in cells lacking phosphatase and tensin homolog function. Heregulin-mediated resistance to GDC-0941 is associated with reactivation of Akt downstream of HER3 phosphorylation. Importantly, combined blockade of HER2 and HER3 signaling by an anti-HER2/HER3 bispecific antibody or a mixture of anti-HER2 and anti-HER3 antibodies restores sensitivity to GDC-0941 in heregulin-treated androgen-dependent and -independent prostate cancer cells. These studies indicate that the combination of PI3K inhibitors with HER2/HER3 targeting antibodies may constitute a promising therapeutic strategy for prostate cancer.

PROSTATE CANCER;

Introduction: A study was done on the prostate cases received in pathologydepartment, Dow Medical College, Dow University of Health Sciences, from different hospitals ofKarachi to see the frequency of prostate cancer. Objectives: Benign hyperplasia prostate iscommon in middle and old age men, while prostate cancer is found more in older age group, itcan occur in middle age also. Methodology: Slides / paraffin blocks were taken for study from 1stJanuary 2008 to 31st December 2011 retrospectively and from 1st January 2012 to 31stDecember 2012 prospectively. Results: In present study 300 cases of prostate slides werestudied in which 274 (91.33%) cases of benign hyperplasia prostate and 26 (8.67%) cases ofprostate carcinoma were found of 46-74 years of age, including 2 (7.70%) cases, of 45 years ofage. Conclusions: It is observed that the increased tendency of prostate carcinoma was foundmore after 50 years of age and in present study 2 cases, of 45 years of age, showing theoccurrence of prostate carcinoma in early age.

Repeat transrectal prostate biopsies in diagnosing prostate cancer

Patients with negative prostate biopsy and persistent suspicion of prostate cancer (PCa) can pose a serious diagnostic problem. The AIM of our study was to determine the frequency of PCa found on repeat prostate biopsy and the factors leading to higher possibility of cancer positive histological result. We studied retrospectively 113 patients (82 from University Clinic, Jena, Germany and 31 from Department of Urology, Plovdiv, Bulgaria) with initial negative biopsy for cancer who underwent repeat biopsies. The patients were examined between January 1999 and May 2010. The target group included patients with Prostate Specific Antigen (PSA) level lower than 12.5 ng/ml and without suspicious finding on digital rectal examination (DRE). Different biopsy schemes were used in the initial and the following biopsies, depending on patient age and total prostate volume. Overall PCa detection rate was 22.1% (25 of 113). The repeat biopsy found PCa in 15.9% (18 of 113). In patients with 3 biopsies the PCa detection rate was considerably lower--only 8.6% (3 of 35). PCa was found in only 1 patient of 18 (5.5%) who underwent four or more biopsies. Transurethral resection of the prostate (TURP) was performed in 15 patients with at least two previously negative biopsies. The pathohistological examination of the resected tissue showed PCa in 3 of the patients (20%). The interval between biopsies is not a significant predictive factor for positive prostate biopsy. The chance for detecting PCa after the second negative transrectal biopsy procedure is low. Therefore, TURP can be used as an alternative procedure to harvest adequate tissue material for pathologic examination, especially in patients with obstructive voiding symptoms.

Truncation of BRAF and Raf1 in prostate cancer in China.

77 Background: Chromosome translocations and fusion genes have been identified as common events in carcinomas in recent years and TMPRSS2:ERG fusions have been found in about half of human prostate cancers. However, by genome-wide analysis of Chinese prostate cancer cases, we found that certain genomic alterations, commonly identified in prostate cancer samples from the Western countries, occurred at a very low frequency in China, including the fusion of TMPRSS2:ERG. In 2010, recurrent fusion genes involving the RAF family gene BRAF and Raf1 were identified (Palanisamy et al, Nature Med. 16:793). Although the frequency of fusions involving BRAF and Raf1 are at a much lower frequency than fusion of TMPRSS2:ERG, BRAF and Raf1 are drugable, making them potential therapeutic targets. As the TMPRSS2:ERG fusion is infrequent in Chinese prostate cancers, we investigated if fusions involving BRAF and Raf1 occur at a higher frequency in prostate cancer in China than in Western countries. Methods: We used the fluorescence in situ hybridization signal split apart approach on prostate cancer samples made into tissue microarrays to detect the frequency of BRAF and Raf1 truncations. Three BAC probes on each side (5’ and 3’) of the two genes were labeled differentially using biotin and digoxigenin and subsequentially detected as red and green fluorescent signals, respectively. Results: We found that BRAF was truncated in four (two split signals, one 5’ deletions and one 3’ deletions) of the 193 informative cases (2.07%) and RAFaf1 (two 5’ deletions and one split signals) was truncated in three of 201 informative cases (1.49%). Although in some cases, three or four copies of these genes were detected, extensive copy number gain caused by amplification was not detected. Conclusions: These results indicate that truncations and potentially fusion of BRAF and Raf1 exist in Chinese prostate cancer, but at a similar low frequency as found in the Western samples (6/349 for BRAF and 4/450 for Raf1). Further studies are required to confirm the functional consequence of these truncations and to evaluate the therapeutic value of targeting these genes in this sub-group of prostate cancers.