Shannon McGrath

Prostate cancer biomarkers: Are we hitting the mark?

Purpose Localised prostate cancer diagnosis and management is increasingly complex due to its heterogeneous progression and prognostic subgroups. Pitfalls in current screening and diagnosis have prompted the search for accurate and invasive molecular and genetic biomarkers for prostate cancer. Such tools may be able to distinguish clinically significant cancers from less aggressive variants to assist with prostate cancer risk stratification and guide decisions and healthcare algorithms. We aimed to provide a comprehensive review of the current prostate cancer biomarkers available and in development. Methods MEDLINE and EMBASE databases searches were conducted to identify articles pertaining to the use of novel biomarkers for prostate cancer. Results A growing number of novel biomarkers are currently under investigation. Such markers include urinary biomarkers, serology-based markers or pathological tissue assessments of molecular and genetic markers. While limited clinical data is present for analysis, early results appear promising. Specifically, a combination of serum and urinary biomarkers (Serum PSA + Urinary PCA3 + Urinary TMPRSS2-ERG fusion) appears to provide superior sensitivity and specificity profiles compared to traditional diagnostic approaches (AUC 0.88). Conclusion The accurate diagnosis and risk stratification of prostate cancer is critical to ensure appropriate intervention. The development of non-invasive biomarkers can add to the information provided by current screening practices and allows for individualised risk stratification of patients. The use of these biomarkers appears to increase the sensitivity and specificity of diagnosis of prostate cancer. Further studies are necessary to define the appropriate use and time points of each biomarker and their effect on the management algorithm of prostate cancer.

Minimally invasive surgical therapies for benign prostatic hypertrophy: The rise in minimally invasive surgical therapies

The prevalence of benign prostatic hypertrophy (BPH) causing bothersome lower urinary tract symptoms increases with our ageing population. Treatment of BPH traditionally begins with medical therapy and surgical intervention is then considered for those whose symptoms progress despite treatment. Minimally invasive surgical therapies have been developed as an intermediary in the treatment of BPH with the aim of decreasing the invasiveness of interventions. These therapies also aim to reduce morbidity and dysfunction related to invasive surgical procedures. Multiple treatment options exist in this group including mechanical and thermo-ablative strategies. Emerging therapies utilizing differing technologies range from the established to the experimental. We review the current literature related to these minimally invasive therapies and the evidence of their effectiveness in treating BPH. The role of minimally invasive surgical therapies in the treatment of BPH is still yet to be strongly defined. Given the experimental nature of many of the modalities, further study is required prior to their recommendation as alternatives to invasive surgical therapy. More mature evidence is required for the analysis of durability of effect of these therapies to make robust conclusions of their effectiveness.

Prostate cancer screening with prostate-specific antigen: A guide to the guidelines

Background Prostate cancer remains the most common non-skin cancer malignancy in men. Prostate-specific antigen (PSA) is recognized as a biomarker for the diagnosis, monitoring, and risk prediction of prostate cancer. Its use in the setting of prostate cancer screening has been controversial due to the risk of over diagnosis and over treatment. Objective Within Australia, there are inconsistent recommendations surrounding the use of PSA screening in clinical practice. In light of the 2016 PSA-screening guidelines by the major Australian health authorities, the current review aims to highlight the controversies and objectively outline the current recommendations within Australia. Discussion Health-care authorities across Australia have issued conflicting guidelines for prostate cancer screening culminating in confusion amongst health care practitioners and members of the public alike. A general consensus is held by other countries across the globe but differences amongst the specific details in how to best employ a PSA screening program still exist.

Prostate Imaging Reporting and Data System score of four or more: active surveillance no more.

This study not only supports the use of olaparib in the treatment of mCPRP but, crucially, Mateo et al. provide further evidence for the feasibility of genetic stratification of patients for treatment. As with the use by Antonarakis et al. [6] of androgen receptor splice variant 7 messenger RNA (AR-V7) to detect response to enzalutamide and abiraterone, next-generation sequencing techniques accurately identified the subset of patients with genetic mutations amenable to PARP inhibition. This increased treatment response from 33 to 88%. Currently recruitment continues for the second part of the trial, TOPARP-B. Potential participants will be screened before commencing olaparib treatment, with only biomarker-positive patients being enrolled. The results of this study will be keenly awaited, but the potential for genetically targeted treatment has now been demonstrated. The role of genetic biomarkers in clinical management algorithms still needs to be established with the potential for genetic stratification extending beyond just treatment. Arguably even more importantly, greater understanding of the genetic basis of prostate cancer will allow more accurate risk stratification modelling. With personalized screening and treatment becoming a reality for patients with prostate cancer, it is to be hoped that the debate over the investigation, diagnosis and treatment of prostate cancer will soon be decided. Conflicts of Interest

Interpreting Prostate Multiparametric Magnetic Resonance Imaging: Urologists' Guide Including Prostate Imaging Reporting and Data System

Abstract Objective To review and explain the development of multiparametric MRI and its use in prostate cancer diagnosis while educating on the implication of certain radiological findings. Methods The physics of MRI is reviewed prior to the explanation of different phase technologies in “multiparametric” scanning. Sample images of the prostate are used to display phenomena described Results modalities of multi-parametric MRI of the prostate were reviewed and the interpretation of certain findings displayed on sample images to educate clinicians about their presence and significance. Conclusions Diagnosis, biopsy targeting, surveillance, operative planning and staging has led to endorsement of mpMRI and it is imperative that treating Urologists have an understanding of mpMRI to appreciate the power and limitations of its findings.

“Plug and Play”: a novel technique utilising existing technology to get the most out of the robot

We describe a simple technique in which current and freely available technology can be utilised by surgeons while operating the Da Vinci Si/Xi Surgical Robotic systems. This technique allows for a parallel intraoperative display within the surgical console of any desired subject material from a standard computer, utilising commercially available cabling. The ability to view 3D reconstructed images, patient radiology and patient results within the console whilst operating, has the potential to increase operative efficiency, reduce error and aid in adequate resection of tissues. The ease with which our technique is achieved, the benefits of its use and the low cost associated with its implementation support our suggestion that all robotic surgeons incorporate this into their regular operative setup.

Transperineal prostate biopsy – tips for analgesia

The modern transperineal prostate biopsy (TPB) technique was first described in 1983(1). Since its introduction, TPB has become favorable over transrectal ultrasound prostate biopsy (TRUS-PB) approach due to higher cancer detection rates particularly in the anterior and transition zones, lower rates of sepsis, and decreased risk of rectal bleeding(2). Using a standardized template for prostate biopsy – sampling of the prostate is improved with TP prostate biopsy when compared to transrectal-guided biopsy(2). This article is protected by copyright. All rights reserved.

Pelvic lymph node dissection during radical cystectomy for muscle-invasive bladder cancer

Radical cystectomy is the gold-standard treatment option for muscle-invasive and metastatic bladder cancer. At the time of cystectomy, up to 25% of patients harbour metastatic lymph node deposits. These deposits most frequently occur in the obturator fossa, but can be as proximal as the interaortocaval region. Thus, the use of concurrent pelvic lymph node dissection (PLND) with cystectomy has been increasingly reported. Data from studies including many patients suggest substantial oncological benefit in PLND cohorts versus non-PLND cohorts, irrespective of pathological nodal status. Additionally, PLND provides useful prognostic information, including disease burden, lymph node density, and extracapsular extension of metastatic lymph nodes. Accordingly, the National Comprehensive Cancer Network guidelines advocate the use of PLND during radical cystectomy for muscle-invasive bladder cancer. Despite this recommendation, a lack of consensus exists regarding the optimal PLND template. Comparative series suggest that extended PLND provides improved recurrence-free survival and cancer-specific survival compared with more limited PLND templates. More extensive templates (such as super-extended PLND) provide no additional survival benefit at the potential cost of increased operative time and patient morbidity. In addition to extended PLND templates, increased nodal harvest confers an oncological benefit in patients with node-positive disease or in patients with node-negative disease. Accordingly, recommendations for a minimum nodal yield have been proposed. Despite the growing body of evidence, formal recommendations by oncological and urological authoritative bodies have been limited owing to the lack of randomized data and level I evidence.Radical cystectomy plus concurrent pelvic lymph node dissection (PLND) provides oncological benefit and useful prognostic information. However, a lack of consensus exists regarding the optimal PLND template. Here, the authors describe and discuss the use of different PLND templates.Key pointsPelvic lymph node dissection (PLND) during radical cystectomy for bladder cancer seems to provide oncological benefit.PLND also provides useful prognostic information, such as tumour burden, lymph node density, and extracapsular extension of metastatic lymph nodes, which can guide management.Extended PLND templates seem to provide optimal recurrence-free and cancer-specific survival, whereas the use of super-extended PLND provides no added benefit.Increased nodal yield improves oncological outcomes in patients with node-negative or node-positive disease.Despite the current evidence, recommendations for optimal PLND techniques during radical cystectomy for muscle-invasive bladder cancer are limited.

EducationInterpreting Prostate Multiparametric MRI: Urologists' Guide Including PIRADS

Abstract Objective To review and explain the development of multiparametric MRI and its use in prostate cancer diagnosis while educating on the implication of certain radiological findings. Methods The physics of MRI is reviewed prior to the explanation of different phase technologies in “multiparametric” scanning. Sample images of the prostate are used to display phenomena described Results modalities of multi-parametric MRI of the prostate were reviewed and the interpretation of certain findings displayed on sample images to educate clinicians about their presence and significance. Conclusions Diagnosis, biopsy targeting, surveillance, operative planning and staging has led to endorsement of mpMRI and it is imperative that treating Urologists have an understanding of mpMRI to appreciate the power and limitations of its findings.

Interpreting Prostate Multiparametric MRI: Urologists' Guide Including PIRADS

Abstract Objective To review and explain the development of multiparametric MRI and its use in prostate cancer diagnosis while educating on the implication of certain radiological findings. Methods The physics of MRI is reviewed prior to the explanation of different phase technologies in “multiparametric” scanning. Sample images of the prostate are used to display phenomena described Results modalities of multi-parametric MRI of the prostate were reviewed and the interpretation of certain findings displayed on sample images to educate clinicians about their presence and significance. Conclusions Diagnosis, biopsy targeting, surveillance, operative planning and staging has led to endorsement of mpMRI and it is imperative that treating Urologists have an understanding of mpMRI to appreciate the power and limitations of its findings.