Patient-derived xenograft (PDX) models have been established as important preclinical cancer models, overcoming some of the limitations associated with the use of cancer cell lines. The utility of prostate cancer PDX models has been limited by an inability to genetically manipulate them in vivo and difficulties sustaining PDX-derived cancer cells in culture. Viable, short-term propagation of PDX models would allow in vitro transfection with traceable reporters or manipulation of gene expression relevant to different studies within the prostate cancer field. Here, we report an organoid culture system that supports the growth of prostate cancer PDX cells in vitro and permits genetic manipulation, substantially increasing the scope to use PDXs to study the pathobiology of prostate cancer and define potential therapeutic targets. We have established a short-term PDX-derived in vitro cell culture system which enables genetic manipulation of prostate cancer PDXs LuCaP35 and BM18. Genetically manipulated cells could be re-established as viable xenografts when re-implanted subcutaneously in immunocompromised mice and were able to be serially passaged. Tumor growth of the androgen-dependent LuCaP35 PDX was significantly inhibited following depletion of the androgen receptor (AR) in vivo. Taken together, this system provides a method to generate novel preclinical models to assess the impact of controlled genetic perturbations and allows for targeting specific genes of interest in the complex biological setting of solid tumors.

ANZ Journal of SurgeryEarly View IMAGES FOR SURGEONS Empyema thoracis: an unreported complication of an infected renal cyst Christina Popovic MBBS, orcid.org/0000-0003-2866-7942 Department of Cardiothoracic Surgery, The Townsville Hospital, Townsville, Queensland, Australia Contribution: Conceptualization, Data curation, Formal analysis, Writing - original draft, Writing - review & editingSearch for more papers by this authorAndre Joshi MBBS, orcid.org/0000-0002-7366-5172 Department of Urology, The Princess Alexandra Hospital, Brisbane, Queensland, Australia Contribution: Conceptualization, Writing - review & editingSearch for more papers by this authorPhilippe Wolanski MBBS, Department of Cardiothoracic Surgery, The Townsville Hospital, Townsville, Queensland, Australia Department of Urology, The Townsville Hospital, Townsville, Queensland, Australia Contribution: Supervision, Writing - review & editingSearch for more papers by this authorAnand Iyer MBBS, Department of Cardiothoracic Surgery, The Townsville Hospital, Townsville, Queensland, Australia Contribution: Conceptualization, SupervisionSearch for more papers by this author Christina Popovic MBBS, orcid.org/0000-0003-2866-7942 Department of Cardiothoracic Surgery, The Townsville Hospital, Townsville, Queensland, Australia Contribution: Conceptualization, Data curation, Formal analysis, Writing - original draft, Writing - review & editingSearch for more papers by this authorAndre Joshi MBBS, orcid.org/0000-0002-7366-5172 Department of Urology, The Princess Alexandra Hospital, Brisbane, Queensland, Australia Contribution: Conceptualization, Writing - review & editingSearch for more papers by this authorPhilippe Wolanski MBBS, Department of Cardiothoracic Surgery, The Townsville Hospital, Townsville, Queensland, Australia Department of Urology, The Townsville Hospital, Townsville, Queensland, Australia Contribution: Supervision, Writing - review & editingSearch for more papers by this authorAnand Iyer MBBS, Department of Cardiothoracic Surgery, The Townsville Hospital, Townsville, Queensland, Australia Contribution: Conceptualization, SupervisionSearch for more papers by this author First published: 26 March 2021 https://doi.org/10.1111/ans.16783Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat No abstract is available for this article. Early ViewOnline Version of Record before inclusion in an issue RelatedInformation

Current in vitro therapeutic testing platforms lack relevance to tumor pathophysiology, typically employing cancer cell lines established as two-dimensional (2D) cultures on tissue culture plastic. There is a critical need for more representative models of tumor complexity that can accurately predict therapeutic response and sensitivity. The development of three-dimensional (3D) ex vivo culture of patient-derived organoids (PDOs), derived from fresh tumor tissues, aims to address these shortcomings. Organoid cultures can be used as tumor surrogates in parallel to routine clinical management to inform therapeutic decisions by identifying potential effective interventions and indicating therapies that may be futile. Here, this procedure aims to describe strategies and a detailed step-by-step protocol to establish bladder cancer PDOs from fresh, viable clinical tissue. Our well-established, optimized protocols are practical to set up 3D cultures for experiments using limited and diverse starting material directly from patients or patient-derived xenograft (PDX) tumor material. This procedure can also be employed by most laboratories equipped with standard tissue culture equipment. The organoids generated using this protocol can be used as ex vivo surrogates to understand both the molecular mechanisms underpinning urological cancer pathology and to evaluate treatments to inform clinical management.

A 75-year-old man was referred to our urology service with painless haematuria. The delayed phase on a subsequent computed tomography (CT) abdomen and pelvis showed a filling defect in the left renal pelvicalyceal system, suspicious for a transitional cell carcinoma. The patient underwent ureteroscopic biopsy suggestive of a papillary neoplasia, before progressing to a laparoscopic radical left nephrouretectomy. Final histology revealed a fumarate hydratase-deficient renal cell carcinoma with clear margins. The patient was subsequently referred for genetic counselling.

Aims: Renal mass biopsy (RMB) is advocated to improve management of small renal masses, however there is concern about its clinical utility. This study aimed to elicit opinions about the role of RMB in small renal mass management from surgeons managing renal cell carcinomas (RCC), and examine the frequency of pre-treatment biopsy in those with RCC. Methods: All surgeons in two Australian states (Queensland: n = 59 and Victoria: n = 108) who performed nephrectomies for RCC in 2012/2013 were sent questionnaires to ascertain views about RMB. Response rates were 54% for Queensland surgeons and 38% for Victorian surgeons. We used medical records data from RCC patients to determine RMB frequency. Results: Most Queensland (81%) and Victorian (59%) surgeons indicated they rarely requested RMB; however 34% of Victorians reported often requesting RMB, compared with no Queensland surgeons. This was consistent with medical records data: 17.6% of Victorian patients with T1a tumours received RMB versus 6.7% of Queensland patients ( p < 0.001). Surgeons’ principal concerns regarding RMB related to sampling reliability (90%) and/or histopathological interpretation (76%). Conclusions: Most surgeons report infrequent use of RMB for small renal masses, however we observed practice variation. The principal reasons for infrequent use were concerns about sampling reliability and histopathological interpretation, which may be valid in regions with less access to interventional radiologists and uropathologists. Further evidence is required to define patient groups for whom biopsy results will alter management. Level of evidence: Not applicable for this multicentre audit.

Background Overactive bladder (OAB) is a common syndrome in the community characterised by unstable bladder contractions, resulting in urinary urgency, frequency and nocturia in the absence of detectable disease. Large studies suggest that >10% of the general population is symptomatic. Objective The aim of this article is to summarise the stepwise treatment for OAB that seeks to improve patient quality of life and reduce patient and health system costs. Discussion OAB is a diagnosis of exclusion that begins with a targeted history and examination of the urogenital system with the aim of assessing the burden of disease on the patient. First-line treatment comprises conservative measures including weight reduction, a decrease in exposure to bladder stimulants, fluid optimisation and pelvic floor exercises. Pharmacological treatments for OAB include anticholinergic medications such as oxybutynin. If the patient is unresponsive to pharmacological treatment, a review by a urology specialist is appropriate. Recommendations may include minimally invasive procedures such as intravesical botulinum toxin A injections, reserving the invasive procedures for patients in specific circumstances.

Men treated for prostate cancer with curative intent face a recurrence rate of up to 53% at 10 years. 68Ga-PSMA imaging is a new technique that can more accurately stage cancer recurrences and facilitate personalised treatment. We evaluated the cost-effectiveness of 68Ga-PSMA PET/MRI for staging men with prostate cancer biochemical recurrence. A cost-effectiveness analysis using a decision-analytic model with Markov chains was constructed. 68Ga-PSMA PET/MRI was compared with usual care in staging of men with suspected prostate cancer recurrence. Men with biochemical recurrence from a study in Brisbane, Australia (n = 30) provided key estimates for the model. The primary outcomes were health system costs and years of life (survival) over 10 years. Deterministic and probabilistic sensitivity analyses were undertaken to address uncertainty in model estimates. On average, a strategy of 68Ga-PSMA was expected to cost AU$56 961(US$39 426) and produce 7.48 life years compared with AU$64 499 (US$44 667) and 7.41 life years in usual care. Therefore, 68Ga-PSMA was potentially cost saving (− AU$7 592 95% UI − $24 846, $7 825) (− US$5 258) and slightly more effective 0.07 life years (95% UI − 0.01, 0.16). The likelihood that 68Ga-PSMA strategy was cost-effective at acceptable thresholds was 87%. The findings were sensitive to the lesion detection rate of the 68Ga-PSMA strategy (52–75%) and the cost of follow up in usual care (AU$1 947 to $2 635). In this exploratory economic evaluation, using 68Ga-PSMA PET/MRI to detect prostate cancer recurrence appears to be cost-effective relative to usual care.

Prospective evidence for the clinical role and efficacy of prostate specific membrane antigen (PSMA) positron emission tomography (PET)/magnetic resonance imaging (MRI) combining MRI characterization and localization of lesions with PET avidity in comparison to conventional imaging is limited. In a prospective clinical trial, we aimed to evaluate the diagnostic yield and therapeutic impact of PSMA PET/MRI in men with biochemical recurrence (BCR) following curative therapy. A single-centre, prospective clinical trial at the Princess Alexandra Hospital recruited 30 patients with BCR. Patients underwent PSMA PET/MRI and concurrent conventional CT chest, abdomen, pelvis and whole-body bone scan. Biopsy was performed when safety possible for histological correlation of identified lesions. Clinical efficacy and impact of PSMA PET findings were evaluated. 30 patients with BCR were recruited (median PSA 0.69 ng/ml). PSMA avid lesions were present in 21 patients (70%). 23 patients were previously treated with definitive surgery, 6 patients received external beam radiotherapy and 1 patient had low dose rate brachytherapy. A total of 8 of 9 lesions biopsied were positive (88.9% histological correlation). PSMA PET/MRI detected local recurrence (p = 0.005) and pelvic lesions (p = 0.06) more accurately than conventional imaging. PSMA PET/MRI may be useful in staging men with biochemical recurrence, especially when PSA is low. Our data demonstrates a high detection rate, especially for locally recurrent disease, and highlights the role of this modality when PSA is low. This modality has the potential to significantly improve prostate cancer detection and may have implications for earlier salvage treatment, avoidance of futile local therapy and change patient management to lead to improved outcomes.

OBJECTIVE:To provide a clinically relevant outline of various current precision medicine principles and available evidence on the application and potential for a precision medicine approach in prostate cancer.METHODS:Narrative review of the current literature in the field.CONCLUSION:Precision medicine is the concept of individualising patient management based on specific tumour characteristics and biology, rather than traditional histological subtypes. The overall aim is to personalise management to individual patients, to provide the right cancer treatment, to the right patient, at the right time. While the approach aims to improve clinical outcomes, decrease morbidity and improve survival in men with advanced prostate cancer, its clinical application is in its infancy. It does however show great promise in this and other cancers, and will continue to be an area of active research and clinical investigation.

Radical prostatectomy (RP) is a common treatment choice for localized prostate cancer. While there is increasing utilisation of robotic assisted RP in some centres, open RP (ORP) remains well established and commonly performed in many parts of the world. The goals of modern ORP are to remove the prostate en-bloc with negative surgical margins, while minimising blood loss and preserving urinary continence and erectile function. We present a technical review of ORP incorporating contemporary techniques for control of the deep venous complex, additional haemostatic measures, nerve-sparing and vesicourethral reconstruction.

Spearman R [ 0.47 and AUC [ 0.78, predicting EPE more accurately than any individual feature and the control model (p [ 0.01). CONCLUSIONS: Tracked biopsy features (i.e. the spatial coordinates of positive and negative cores), when used alongside other clinical parameters, improved prediction of PCa volume and stage. These metrics, once validated in prospective trials, may improve PCa risk classification and disease management.

Metastatic renal cell carcinoma (mRCC) is a disease that portends poor prognosis despite an increasing number of novel systemic treatment options including new targeted therapies and immunotherapy. Ablative intervention directed at oligometastatic RCC has demonstrated survival benefit. Consequently, developing techniques for improved staging of mRCC on contemporary imaging modalities including X-ray computed tomography (CT), magnetic resonance imaging (MRI) and/or bone scan (BS) is a clinical priority. This is relevant for metastatic deposits too small to characterize or lymph nodes within physiological normality. Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein highly expressed on prostate cancer epithelial cells. Recently, small molecules targeting the PSMA receptor, linked to radioactive isotopes have been developed for use with positron emission tomography (PET). Despite its nomenclature, PSMA has also been found to be expressed in the neovasculature of non-prostate cancers such as renal cell carcinoma (RCC) and hence PSMA PET/CT imaging has been proposed as an alternative staging modality. Preliminary small studies involving the use of PSMA PET/CT imaging in mRCC have been encouraging with evidence of improved staging sensitivity which has directly led to change in management in some cases. Given these early encouraging reports, we performed a comprehensive narrative review on the available evidence, including the scientific basis for PSMA expression in RCC, the role of PSMA PET/CT imaging with potential clinical implications in mRCC, its limitations and future opportunities.

To describe national surgical patterns of prostate cancer (PCa) care considering radical prostatectomy with or without pelvic lymphadenectomy and consideration of robotic‐assisted techniques.

You have accessJournal of UrologyProstate Cancer: Detection & Screening V (MP36)1 Apr 2019MP36-17 DEFINING BIOCHEMICAL RECURRENCE IN PROSTATE CANCER WITH HYBRID PSMA PET MRI Paria Saadat, Georges Mehawed*, Michelle Ong, Andre Joshi, Matthew Roberts, Marlon Perera, Handoo Rhee, Yeates Alexander, Ian McKenzie, Janelle Munns, Greg Malone, Eric Chung, Peter Heathcote, John Preston, Lawson Malcolm, Simon Wood, David Pryor, Margot Lehman, Gustafson Sonja, Kenneth Miles, Stanley Ngai, and Ian Vela Paria SaadatParia Saadat More articles by this author , Georges Mehawed*Georges Mehawed* More articles by this author , Michelle OngMichelle Ong More articles by this author , Andre JoshiAndre Joshi More articles by this author , Matthew RobertsMatthew Roberts More articles by this author , Marlon PereraMarlon Perera More articles by this author , Handoo RheeHandoo Rhee More articles by this author , Yeates AlexanderYeates Alexander More articles by this author , Ian McKenzieIan McKenzie More articles by this author , Janelle MunnsJanelle Munns More articles by this author , Greg MaloneGreg Malone More articles by this author , Eric ChungEric Chung More articles by this author , Peter HeathcotePeter Heathcote More articles by this author , John PrestonJohn Preston More articles by this author , Lawson MalcolmLawson Malcolm More articles by this author , Simon WoodSimon Wood More articles by this author , David PryorDavid Pryor More articles by this author , Margot LehmanMargot Lehman More articles by this author , Gustafson SonjaGustafson Sonja More articles by this author , Kenneth MilesKenneth Miles More articles by this author , Stanley NgaiStanley Ngai More articles by this author , and Ian VelaIan Vela More articles by this author View All Author Informationhttps://doi.org/10.1097/01.JU.0000556027.16655.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVES: Biochemical recurrence (BCR) can occur in in up to 50% or more of men with high risk prostate cancer previously treated with surgery of curative intent. Detection of locally recurrent or metastatic disease in the presence of BCR after treatment of localised disease at low prostate specific antigen (PSA) may be improved by use of hybrid Prostate Specific Membrane Antigen (PSMA), Positron Emission Tomography (PET) with magnetic resonance imaging (MRI). The clinical utility of this approach has been minimally reported. We sought to report on a large series of hybrid PSMA PET MRI in defining BCR. METHODS: Following Institutional Research Board approval, a retrospective review of all PSMA PET MRI studies between April 2015 and April 2017 within a tertiary referral institution was conducted. Clinical variables, including patient demographics, PSA, previous treatment and histology prior to scan, indication for scan, imaging results, and outcome post imaging were collected prior to statistical analysis. RESULTS: A total of 300 PSMA PET MRI scans were performed, of which 135 were to investigate BCR. Sixty-four patients had undergone radical prostatectomy with a median PSA of 0.43 ng/ml (Interquartile Range (IQR) = 0.21 - 1.35), in whom 15 received postoperative external beam radiation therapy (EBRT) while 71 patients had received EBRT alone. From the surgical cohort, 31 patients (48.5%) had a positive scan (median PSA level 1.3 ng/ml, IQR = 0.26 – 4; Gleason score 4 + 4 in 17 patients) involving the prostatic bed (n = 6), lymph nodes (n = 18), bone (n = 6), and soft tissue (n = 11), for median serum PSAs of 1.8, 1.35, 1.6 and 0.4 ng/mL, respectively. Median PSA for those with a negative scan was 0.28 ng/mL (IQR = 0.17 – 0.57), despite 10 patients (30%) with a Gleason score 4 + 4. CONCLUSIONS: PSMA PET MRI imaging may play an important role in detecting recurrent disease in men with BCR post radical prostatectomy. The average PSA for detection of metastatic lesions are substantially less than previously quoted figures using the standard of care imaging in the setting of biochemical recurrence. Source of Funding: None. South Brisbane, Australia; Brisbane, Australia© 2019 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 201Issue Supplement 4April 2019Page: e520-e521 Advertisement Copyright & Permissions© 2019 by American Urological Association Education and Research, Inc.MetricsAuthor Information Paria Saadat More articles by this author Georges Mehawed* More articles by this author Michelle Ong More articles by this author Andre Joshi More articles by this author Matthew Roberts More articles by this author Marlon Perera More articles by this author Handoo Rhee More articles by this author Yeates Alexander More articles by this author Ian McKenzie More articles by this author Janelle Munns More articles by this author Greg Malone More articles by this author Eric Chung More articles by this author Peter Heathcote More articles by this author John Preston More articles by this author Lawson Malcolm More articles by this author Simon Wood More articles by this author David Pryor More articles by this author Margot Lehman More articles by this author Gustafson Sonja More articles by this author Kenneth Miles More articles by this author Stanley Ngai More articles by this author Ian Vela More articles by this author Expand All Advertisement PDF downloadLoading ...

Ureteral stents are an essential tool in modern day adult and paediatric urology. They are usually placed with the intention of removal or replacement after a specific time but may occasionally be forgotten or unintentionally retained. We present the case of a young man who presented with symptoms caused by a retained ureteric stent placed 26 years earlier during reconstructive ureteric surgery as an infant.