A polygenic two-hit hypothesis for prostate cancer.

Prostate cancer is one of the most heritable cancers. Hundreds of germline polymorphisms have been linked to prostate cancer diagnosis and prognosis. Polygenic risk scores can predict genetic risk of a prostate cancer diagnosis.

The Impact of Whole Genome Data on Therapeutic Decision-Making in Metastatic Prostate Cancer: A Retrospective Analysis.

Background: While critical insights have been gained from evaluating the genomic landscape of metastatic prostate cancer, utilizing this information to inform personalized treatment is in its infancy. We performed a retrospective pilot study to assess the current impact of precision medicine for locally advanced and metastatic prostate adenocarcinoma and evaluate how genomic data could be harnessed to individualize treatment.

Methods: Deep whole genome-sequencing was performed on 16 tumour-blood pairs from 13 prostate cancer patients; whole genome optical mapping was performed in a subset of 9 patients to further identify large structural variants.

Androgen deprivation therapy promotes an obesity-like microenvironment in periprostatic fat.

Prostate cancer is a leading cause of morbidity and cancer-related death worldwide. Androgen deprivation therapy (ADT) is the cornerstone of management for advanced disease. The use of these therapies is associated with multiple side effects, including metabolic syndrome and truncal obesity.

Lessons Learned and New Challenges: Re-evaluation of End-User Assessment of a Skills-Based Training Program for Urology Trainees.

Objectives: To re-assess the perceived benefit and relevance of simulation sessions to Victorian urology trainees and to identify areas for potential improvement.

Subjects And Methods: All trainees attending skills training sessions between 2011 and 2016 were asked to complete a structured questionnaire at the completion of the session. The questionnaire included 11 topic areas ranging from the year of surgical training to degree of usefulness of the session, including several sections for free-text response to offer more detailed feedback.

Prostatic nerve subtypes independently predict biochemical recurrence in prostate cancer.

Objective: To describe nerve subtypes involved by perineural invasion (PNI) in prostate cancer and their relationship with clinicopathological parameters and recurrence risk.

Methods: 141 prostatectomy specimens from men with localized prostate cancer and known perineural invasion were analyzed. Index tumor blocks were stained for perineural invasion and sympathetic/parasympathetic markers.

Preparation of fluorescent in situ hybridisation probes without the need for optimisation of fragmentation.

DNA-fluorescence in situ hybridisation (DNA-FISH) allows visualisation of chromosome organisation and rearrangement. FISH probes are pools of short fluorescently labelled DNA fragments that are often produced from template plasmids that contain large genomic inserts. For effective sample penetration and target hybridisation it is critical that probe fragments are between 200 and 500bp.

Developments in oligometastatic hormone-sensitive prostate cancer.

Purpose: To review the current understanding and recent developments regarding the concept of oligometastases in hormone-sensitive prostate cancer.

Methods: A comprehensive literature search of electronic databases, including PubMed and Embase was conducted for the search term 'oligometastases' in combinations with 'prostate cancer', 'hormone sensitive', 'genetics', and 'molecular'. All articles relating to these search terms have been taken into account.

Late biochemical recurrence after radical prostatectomy is associated with a slower rate of progression.

Objective: To characterise the pattern of late biochemical recurrence (BCR) in the largest contemporary cohort of patients with localised prostate cancer treated with radical prostatectomy (RP) in the active surveillance era.

Patients And Methods: Consecutive patients who underwent RP for localised prostate cancer between 2003 and 2017 were identified from a prospectively recorded, dedicated prostate cancer database. Patients who received neoadjuvant androgen-deprivation therapy were excluded.

Does partnership status affect the quality of life of men having robotic-assisted radical prostatectomy (RARP) for localised prostate cancer?

Objective: To investigate whether there are any differences in prostate cancer-specific QoL measures at baseline and at 12-months post-surgery between partnered and unpartnered men having robot-assisted radical prostatectomy (RARP) for localised prostate cancer.

Methods: We investigated differences in patient-reported outcomes using the Expanded Prostate cancer Index Composite-26 (EPIC-26) and the Clark et al. Prostate Cancer Quality of Life Scales.

Obesity suppresses tumor attributable PSA, affecting risk categorization.

Obesity is linked with more aggressive prostate cancer and higher rates of disease recurrence post treatment. It is unclear if this is due to specific tumor-promoting effects of obesity or diagnostic bias. Patients undergoing prostatectomy were categorized according to their body mass index (BMI).

Periprostatic fat tissue transcriptome reveals a signature diagnostic for high-risk prostate cancer.

Evidence suggests that altered adipose tissue homeostasis may be an important contributor to the development and/or progression of prostate cancer. In this study, we investigated the adipose transcriptional profiles of low- and high-risk disease to determine both prognostic potential and possible biological drivers of aggressive disease. RNA was extracted from periprostatic adipose tissue from patients categorised as having prostate cancer with either a low or high risk of progression based on tumour characteristics at prostatectomy and profiled by RNA sequencing.

Mitochondrial genome variation and prostate cancer: a review of the mutational landscape and application to clinical management.

Prostate cancer is a genetic disease. While next generation sequencing has allowed for the emergence of molecular taxonomy, classification is restricted to the nuclear genome. Mutations within the maternally inherited mitochondrial genome are known to impact cancer pathogenesis, as a result of disturbances in energy metabolism and apoptosis.

Modulation of paracrine signaling by CD9 positive small extracellular vesicles mediates cellular growth of androgen deprived prostate cancer.

Proliferation and maintenance of both normal and prostate cancer (PCa) cells is highly regulated by steroid hormones, particularly androgens, and the extracellular environment. Herein, we identify the secretion of CD9 positive extracellular vesicles (EV) by LNCaP and DUCaP PCa cells in response to dihydrotestosterone (DHT) and use nano-LC-MS/MS to identify the proteins present in these EV. Subsequent bioinformatic and pathway analyses of the mass spectrometry data identified pathologically relevant pathways that may be altered by EV contents.

Extracellular vesicles for personalized therapy decision support in advanced metastatic cancers and its potential impact for prostate cancer.

The use of circulating tumor cells (CTCs) and circulating extracellular vesicles (EVs), such as exosomes, as liquid biopsy-derived biomarkers for cancers have been investigated. CTC enumeration using the CellSearch based platform provides an accurate insight on overall survival where higher CTC counts indicate poor prognosis for patients with advanced metastatic cancer. EVs provide information based on their lipid, protein, and nucleic acid content and can be isolated from biofluids and analyzed from a relatively small volume, providing a routine and non-invasive modality to monitor disease progression.

Androgen synthesis in prostate cancer: do all roads lead to Rome?

The accumulation of high concentrations of signalling androgens within prostate tumours that progress despite use of androgen-deprivation therapy is a clinically important mechanism of the development of castration-resistant prostate cancer. In the past 5 years, data from a number of studies have increased our understanding of the enzymes and substrates involved in intratumoural androgen biosynthesis, and have implicated three competing pathways, which are likely to account for these observations. These pathways ('canonical', 'backdoor' and '5α-dione'), which can all ultimately generate the potent signalling androgen, dihydrotestosterone, involve many of the same enzymes, but differ in terms of substrate preference, reaction sequence and the organs and tissues in which they occur.

Routinely reported 'equivocal' lymphovascular invasion in prostatectomy specimens is associated with adverse outcomes.

Objective: To evaluate the significance of routinely reported 'equivocal' lymphovascular invasion (LVI) in prostatectomy specimens of patients with clinically localized prostate cancer.

Materials And Methods: Prospectively collected data from men who underwent prostatectomy for clinically localized prostate cancer were retrospectively reviewed. Rates of adverse pathological features and biochemical recurrence (BCR) were compared between tumours positive, negative or 'equivocal' for LVI.

Reduction in expression of the benign AR transcriptome is a hallmark of localised prostate cancer progression.

Background: Despite the importance of androgen receptor (AR) signalling to prostate cancer development, little is known about how this signalling pathway changes with increasing grade and stage of the disease.

Objective: To explore changes in the normal AR transcriptome in localised prostate cancer, and its relation to adverse pathological features and disease recurrence.

Design: Publically accessible human prostate cancer expression arrays as well as RNA sequencing data from the prostate TCGA.

A prospective study of the short-term quality-of-life outcomes of patients undergoing transperineal prostate biopsy.

Objective: To investigate in a prospective, observational study whether transperineal prostate biopsy (TPbx) results in patient-reported quality-of-life (QoL) changes from baseline in the first 3-months after TPbx.

Patients And Methods: Consenting patients completed the 26-item Expanded Prostate cancer Index Composite (EPIC-26), the Sexual Health Inventory for Men, the International Prostate Symptom Score, the Generalised Anxiety Disorder seven-item scale, the Patient Health Questionnaire nine-item scale, and a global question about willingness to have a repeat TPbx in a years' time. The instruments were scored using published scoring methods.

Does perineural invasion in a radical prostatectomy specimen predict biochemical recurrence in men with prostate cancer?

Introduction: The ability of perineural invasion (PNI) in radical prostatectomy (RP) specimens to predict biochemical recurrence (BCR) is unclear. This study investigates this controversial question in a large cohort.

Methods: A retrospective analysis was undertaken of prospectively collected data from 1497 men who underwent RP (no neoadjuvant therapy) for clinically localized prostate cancer.

"We Used a Validated Questionnaire": What Does This Mean and Is It an Accurate Statement in Urologic Research?

Objective: To educate a clinical audience of what the specific meaning of the term "validated questionnaire" means from a research methodology perspective when used in a journal article or a conference presentation.

Methods: To emphasize what is meant by the term "validated questionnaire," we reviewed the most commonly used prostate-specific, patient-reported, outcome assessment instruments and discuss which have been appropriately validated for use in patients having surgery for localized prostate cancer.

Results: Not all the prostate-specific instruments used to assess outcomes after surgical treatment for localized prostate cancer have been validated for use in this population.

Canonical androstenedione reduction is the predominant source of signaling androgens in hormone-refractory prostate cancer.

Purpose: It has been recognized for almost a decade that concentrations of signaling androgens sufficient to activate the androgen receptor are present in castration-resistant prostate cancer tissue. The source of these androgens is highly controversial, with three competing models proposed. We, therefore, wished to determine the androgenic potential of human benign and malignant (hormone-naïve and treated) prostate tissue when incubated with various precursors and examine concomitant changes in enzyme expression.

Error rates in a clinical data repository: lessons from the transition to electronic data transfer--a descriptive study.

Objective: Data errors are a well-documented part of clinical datasets as is their potential to confound downstream analysis. In this study, we explore the reliability of manually transcribed data across different pathology fields in a prostate cancer database and also measure error rates attributable to the source data.

Design: Descriptive study.

A randomised, wait-list controlled trial: evaluation of a cognitive-behavioural group intervention on psycho-sexual adjustment for men with localised prostate cancer.

Objective: To examine the effectiveness of a cognitive-behavioural therapy (CBT) group intervention to facilitate improved psycho-sexual adjustment to treatment side effects in prostate cancer survivors post-radical prostatectomy.

Methods: A randomised, wait-list controlled trial was conducted with a total of 60 men who participated in a manualised 8-week cognitive-behavioural group intervention 6 months to 5 years post-radical prostatectomy for localised prostate cancer. Participants completed standardised questionnaires pre-intervention and post-intervention, which assessed mood state, stress, general and prostate cancer anxiety, quality of life and areas of sexual functioning.