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Background: Transrectal (TR) and transperineal (TP) approaches for prostate biopsy have different morbidity profiles. Our institution transitioned to a preference for multiparametric MRI-based triage and TP biopsy since 2014. The aim of this study was to compare clinical, microbiological and health economic outcomes between TR and TP prostate biopsy., Methods: A consecutive cohort study considered prostate biopsies over an 11 year period. Hospital presentations across the region within 30 days of biopsy were analysed for details and subsequent outcomes according to biopsy approach. Cost for each encounter (routine and unplanned) were analysed and generalised linear models applied, as well as cost implications for inclusion of mpMRI-based triage and TP biopsy preference., Results: In total, 2048 prostate biopsies were performed. Similar re-presentation rates per occurred for each biopsy approach (90 patients, TR 4.8%, TP 3.8%, p = 0.29), with 23 patients presenting more than once (119 total presentations). Presentations after TR biopsy were more likely to be of infectious aetiology (TR 2.92%, TP 0.26% de novo, p < 0.001) and result in hospital admission (TR 43/49, 93.4%; TP 14/24, 58.3%; p = 0.007) for similar rates of urinary retention (TR 2.76% vs TP 3.63%, p = 1). The mean overall cost (biopsy and re-presentations) was higher for the TP group (p < 0.001), adjusted for year and age, but reduced over time and was similar for patients who re-presented (p = 0.98). Incorporation of mpMRI (with subsequently avoided biopsies), TP biopsy and re-presentations resulted in AU$783.27 saving per biopsy., Conclusions: TR biopsy resulted in more infectious complications and hospital admissions than TP biopsy for similar rates of re-presentation and urinary retention. TP biopsy costs reduced over time and use in conjunction with mpMRI provides an overall cost saving. Routine TP biopsy is safe and feasible, with further cost savings expected with other approaches (local anaesthetic) under investigation.

Grading is one of the best prognostic indicators of prostate cancer with Gleason grade 5 having the worst outcome. The prognostic influence of grade 5 patterns remains uncertain. A total of 646 prostate needle biopsy sets with Gleason score (GS) 9-10 prostatic adenocarcinoma were prospectively analysed. Patterns of grade 5 were correlated with radical prostatectomy (RP) adverse findings of high tumour volume (TV), extra-prostatic extension (EPE), seminal vesicle invasion (SVI) and lymph node involvement (LNI) in 472 and biochemical recurrence (BCR) in 338 patients after RP. Mean age and serum PSA were 69 years (range 37-91) and 26.1 ng/mL (range 1.4-1800), respectively. Gleason scores were 4+5=9 in 539 (83%), 5+4=9 in 94 (15%) and 5+5=10 in 13 cases (2%). Clusters/cords, single cells, sheets and comedocarcinoma were found in 86%, 69%, 26% and 18% with a pure pattern in 25% of cases. Comparing cases with and without sheets, there were no significant differences with RP high TV (p=0.8577), EPE (p=0.5372), SVI (p=0.5183) and LNI (p=0.4323). However, the presence of sheets predicted a significantly higher BCR rate (p=0.0033), while for tumours with single cells, the interval to BCR was significantly shorter (p<0.0001). Comparing cases with and without the other patterns, two other significant differences were found. Comedocarcinoma predicted high TV (p=0.0230) and single cells predicted EPE (p=0.0101). This study shows that all patterns currently used to assign a Gleason grade 5, including sheets, comedocarcinoma, single cells and clusters/cords, are associated with aggressive outcomes validating their inclusion in grade 5., (Copyright © 2020 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Formal staging classifications for renal cell carcinoma (RCC) were first proposed in 1978 and were incorporated into the Tumour, Nodes, Metastases (TNM) system initially published by the Union Internationale Contre le Cancer (UICC) in 1978. There has been a gradual evolution of grading criteria through six separate editions of the UICC TNM Classification, with the latest edition being published in 2016. Somewhat surprisingly there were no changes to the T category criteria from the 2009 to the 2016 editions of the classification, although an erratum has subsequently been published that incorporated the minor changes included in the eighth edition of the TNM Classification published by the American Joint Committee on Cancer. Localised tumours are staged according to the size of the primary tumour, with the TNM classification recognising that these tumours may exceed 10 cm in diameter. This is unfortunate as there is good evidence to demonstrate that, for clear cell RCC, virtually all tumours >7 cm in diameter and a substantial proportion of tumours <7 cm in diameter, show extra-renal spread. Infiltration of tumour beyond the renal capsule into the peri-renal fat is also categorised as T3a, however the clinical importance of this remains unclear. The classification of microvascular invasion within the renal sinus requires clarification, as does the prognostic significance of tumour in small vessels within the kidney., (Copyright © 2020 Royal College of Pathologists of Australasia. All rights reserved.)

There are a number of benign epithelial proliferations in the bladder that may be difficult to distinguish from carcinomas, including urothelial carcinoma and its variants, squamous cell carcinoma and adenocarcinoma. If misdiagnosed, there is the potential for over treatment, with its attendant risk of complications, as well as errors relating to prognostic assessment. In the case of the misdiagnosis of high grade proliferative lesions that mimic invasive carcinoma, unnecessary radical surgery, chemotherapy and radiotherapy may result. Similarly, the misdiagnosis of lesions that have the appearance of low grade carcinoma can prompt a lifetime of radiological investigation and cystoscopies. In this review, we discuss a variety of entities that may be diagnostically challenging and emphasise the importance of identifying key morphological features that have diagnostic utility. We also highlight the importance of relevant clinical information and the clinical settings in which these lesions may occur. In this review we have divided the lesions on the basis of morphology in order to facilitate discussion relating to the differential diagnosis. The architectural patterns we discuss include papillary lesions (polypoid/papillary cystitis and papillary urothelial hyperplasia), pseudocarcinomatous proliferations (pseudocarcinomatous urothelial hyperplasia, florid proliferation of von Brunn nests and fibroepithelial polyps), glandular lesions (intestinal metaplasia and müllerianosis) and lesions with several different patterns (prostatic type urethral polyps and nephrogenic adenoma or metaplasia)., (Copyright © 2020 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate the ability of preoperative multiparametric magnetic resonance imaging (mpMRI) and a gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography ( 68 Ga-PSMA PET/CT) scan to predict pathological outcomes and also identify a group of men with a <5% risk of histological pelvic lymph node metastasis (LNM) at pelvic lymph node dissection (PLND) performed during a robot-assisted laparoscopic radical prostatectomy (RALP) for prostate cancer. We then aimed to compare these results to known risk calculators for LNM, including the Cancer of the Prostate Risk Assessment (CAPRA) score, Memorial Sloan Kettering Cancer Centre (MSKCC) and Briganti nomograms., Patients and Methods: Between July 2014 and September 2019 only men who had both a preoperative mpMRI and staging 68 Ga-PSMA PET/CT at our institution followed by a RALP with PLND referred to a single specialist uropathology laboratory were considered for inclusion. The data were collected retrospectively prior to February 2019 and in a prospective manner thereafter. A model was built to allocate probabilities of the men with a negative 68 Ga-PSMA PET/CT scan having a <5% risk of histologically LNM at RALP based on the preoperative radiological staging., Results: A total of 233 consecutive men met the inclusion criteria of which 58 men (24.9%) had a LNM identified on PLND histology. The median (range) International Society of Urological Pathology (ISUP) Grade was 5 (1-5) and the median (range) prostate-specific antigen level was 7.4 (1.5-72) ng/mL. The median (range) number of resected lymph nodes was 16 (1-53) and the median (range) number of positive nodes identified on histology was 2 (1-22). Seminal vesicle invasion on mpMRI was more common in node-positive men than in the absence of LNM (31% vs 12%). The maximum standardised uptake value of the primary tumour on 68 Ga-PSMA PET/CT was higher in men with LNM (median 9.2 vs 7.2, P = 0.02). Suspected LNM were identified in 42/233 (18.0%) men with 68 Ga-PSMA PET/CT compared with 22/233 (9.4%) men with mpMRI (P = 0.023). The positive and negative predictive value for 68 Ga-PSMA PET/CT was 66.7% and 84.3% respectively, compared to 59.1% and 78.7% for mpMRI. A predictive model showed only two men (4.2%) with a negative preoperative 68 Ga-PSMA PET/CT would be positive for a histological LNM if they are ISUP Grade < 5 and Prostate Imaging-Reporting and Data System (PI-RADS) <5; or ISUP Grade 5 with PI-RADS < 4. An inspection of three additional variables: CAPRA score, MSKCC and Briganti nomograms did not improve the predictive probability for this group. However, of the 61 men with ISUP Grade 4-5 malignancy and also a PI-RADS 5 mpMRI, 20 (32.8%) men had a microscopic LNM despite a negative preoperative 68 Ga-PSMA PET/CT., Conclusion: Preoperative 68 Ga-PSMA/PET CT was more sensitive in identifying histological pelvic LNM than 3-T mpMRI. Men with a negative 68 Ga-PSMA PET/CT have a lower risk of LNM than predicted with CAPRA scores or MSKCC and Briganti nomograms. We identified that the combination of a negative preoperative 68 Ga-PSMA PET/CT, ISUP biopsy Grade <5 and PI-RADS <5 prostate mpMRI, or an ISUP Grade 5 with PI-RADS <4 on mpMRI was associated with a <5% risk of a LNM. The addition of CAPRA scores, MSKCC and Briganti nomograms did not improve the predictive probability within this model. Conversely, men with ISUP Grade 4-5 malignancy associated with a PI-RADS 5 prostate mpMRI had a >30% risk of microscopic LNM despite a negative preoperative 68 Ga-PSMA PET/CT and this high-risk group would appear suitable for an extended PLND at the time of a radical prostatectomy., (© 2020 The Authors BJU International © 2020 BJU International Published by John Wiley & Sons Ltd.)

The histopathological diagnosis of prostatic adenocarcinoma is challenged by the existence of numerous benign mimics. Most of these lesions have no clinical significance and many do not need to be reported. Their clinical relevance lies in the risk that they are misinterpreted as cancer. This review presents the histopathological features of benign mimics and discusses their distinction from cancer. The lesions that are most often misdiagnosed as cancer are atrophy and its variants, including simple atrophy, partial atrophy and post-atrophic hyperplasia. Benign proliferations are a group of lesions with crowded small glands with no or little nuclear atypia. The most problematic entity of this group is adenosis, which may have a more alarming architecture than some cancers. A diagnostic problem with atrophy and several of the benign proliferations is that the glands often have a discontinuous or absent basal cell layer. Hyperplastic and metaplastic lesions include basal cell hyperplasia. Basal cell hyperplasia may especially mimic prostate cancer with its small dark glands, variable nuclear atypia and a pseudoinfiltrative pattern, which may be present. The anatomical structure that most often causes diagnostic problems is the seminal vesicle. The mucosa of the seminal vesicle contains small acini, often with very pronounced nuclear atypia that may be misinterpreted as cancer. Pathologists need to be familiar with these mimics, as a false positive diagnosis of prostate cancer may lead to unnecessary radical treatment., (Copyright © 2020 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Foci of necrosis are frequently seen in malignant tumours and may be due to a variety of causes. Different types of necrosis are given various names based upon their morphological features and presumed pathogenesis, such as coagulative, liquefactive and fibrinoid necrosis. Here, we propose the term 'granular necrosis' (GN) for a specific form of tumour necrosis characterised by the presence of well-defined necrotic foci being sharply demarcated from adjacent viable tumour. A constant feature is loss of architecture resulting in an amorphous necrotic mass containing granular nuclear and cytoplasmic debris, without an associated neutrophilic infiltrate. There is usually extensive karyorrhexis, which in larger tumours is more prominent at the periphery. These foci are often microscopic but may range up to several millimetres or larger in size. This distinctive form of necrosis has been erroneously given a variety of names in the literature including coagulative necrosis and microscopic necrosis, which on the basis of the aforementioned gross and microscopic findings is inappropriate. It is apparent that this is a specific form of necrosis, hence the descriptive term 'granular necrosis' that differentiates this form of necrosis from other types. The presence of GN is recognised as occurring in a variety of tumour types, being commonly seen in renal cell carcinoma, where it has been shown to have independent prognostic significance. In some epithelial and stromal tumours of the uterus, the presence of GN also has prognostic significance and is a defining feature for the differentiation of uterine leiomyoma and leiomyosarcoma. The pathogenesis of GN is unresolved. It does not show the features of apoptosis and in recent studies has been shown to have some of the molecular changes associated with necroptosis., (Copyright © 2020. Published by Elsevier B.V.)

Infiltration of the prostatic ducts by prostatic adenocarcinoma occurs relatively frequently, being most commonly associated with high grade disease. It is now recognised that intraductal carcinoma of the prostate (IDCP) has an associated poor prognosis and this is reflected in its histological, molecular and immunohistochemical features. The current recommendation of the World Health Organization is that IDCP not be taken into consideration when grading prostate adenocarcinoma. It is apparent that Gleason did not differentiate between IDCP and stromal invasive carcinoma when developing and validating his grading system, and recent studies suggest that the incorporation of IDCP grading into the overall grading of the specimen provides additional prognostic information., (Copyright © 2019 Royal College of Pathologists of Australasia. All rights reserved.)

Purpose: The role of 68 Ga-PSMA PET/CT in the staging of prostate cancer is well known. PSMA is also overexpressed in the neovasculature of other tumours including renal cell carcinoma (RCC), suggesting there may be a role for the use of 68 Ga-PSMA PET/CT. Thus far, there has been limited literature documenting the use of 68 Ga-PSMA PET/CT in the investigation and management decisions of RCC., Methods: This was a retrospective case series of patients who received a 68 Ga-PSMA PET/CT scan for staging or restaging of RCC between July 2016 and December 2018. Primary outcome measure was to identify whether 68 Ga-PSMA PET/CT changed management compared to standard diagnostic CT imaging. Analysis was based on four categories: (1) identification of new disease, (2) refuting disease on CT imaging, (3) identification of synchronous primaries, and (4) concordance with CT imaging., Results: 38 68 Ga-PSMA PET/CT scans met inclusion criteria. Primary staging scans were performed in 16 patients, of which 75% showed avid primary lesions, with the majority of clear cell subtype. Management was changed in 43.8% of patients. CT agreed with 68 Ga-PSMA PET/CT in 37.5% of cases. Restaging scans were performed in 22 patients. 40.9% of patients had management changed by results of 68 Ga- PSMA PET/CT. CT agreed with 68 Ga- PSMA PET/CT in 36.4% of cases. Management was predominantly changed due to the identification of new sites of suspected metastases, as well as the detection of synchronous primaries., Conclusions: 68 Ga-PSMA PET/CT directly changed management in 42.1% of cases. Strongest detection rates occurred in those patients with clear cell RCC. The results of this study suggest there may be merit in the use of the modality in the staging of RCC. Further analysis, both with respect to histological confirmation, efficacy and cost-benefit, is required to determine whether there is a role for routine 68 Ga-PSMA PET/CT imaging.

Background: 68 Ga-PET/CT PSMA scan is being increasingly used for the staging of biochemically recurrent disease. Early identification of recurrent disease after radiotherapy is important in considering suitability for early salvage therapy to improve prognosis. The aim is to identify patterns of suspected prostate cancer recurrence in relation to post-radiotherapy PSA levels, especially below the accepted Phoenix definition of PSA failure (PSA nadir + 2)., Methods: This was a retrospective single tertiary institution cohort study of consecutive men between July 2014 and June 2018 who received a 68 Ga-PSMA PET/CT for elevated PSA levels following radiotherapy as primary treatment of prostate cancer. The primary outcome measure was to determine the relationship between pre-scan PSA and the probability of identifying PSMA-avid disease suggestive of recurrent prostate cancer., Results: Two hundred and seventy-six patients met criteria for inclusion. The median PSA was 3.60 ng/mL. The overall detection rate for suspected recurrent prostate cancer was 86.3%. Local recurrence was the most common site, occurring in 56.9% (157/276) of men, with isolated local recurrence in 32.6% (90/276). A total of 75.3% (55/73) of men below Phoenix criteria had scans suggestive of recurrent disease, with 52.1% of men having salvageable disease. The regions surrounding the iliac arteries were the most common areas of nodal metastatic disease, with 55.6% of recurrence occurring in the iliac regions., Conclusions: 68 Ga-PSMA PET/CT frequently identifies suspected recurrent disease prior to the accepted Phoenix definition of PSA nadir +2. Prospective outcome studies are required to determine if early identification of local recurrence improves outcomes by increasing the use of salvage local treatments and whether earlier identification of metastatic disease may improve outcomes with prompt initiation of multimodality therapies.

This study was undertaken to determine the association between extrarenal tumor spread and size in a series of well-sampled clear cell renal cell carcinoma (ccRCC). In a series of 917 cases of ccRCC, 178 were >7 cm in maximum extent. Assessment of tumors >7 cm in size showed 72 (40.4%) to have renal sinus infiltration, the tumor infiltrating perirenal fat in 7 (3.9%) cases, and both in 96 (53.9%) cases. In the remaining 3 (1.7%) cases, no extrarenal extension of the tumor was seen. These 3 cases with organ-confined ccRCC were all cystic tumors. Two showed extensive infarction with associated hemorrhage and the presence of a thick investing pseudocapsule, while the third was a cystic ccRCC arising in the upper pole of the kidney. For the ccRCCs in the series that were ≤7 cm in maximum extent, division of cases according to tumor size and pT staging category showed an increase in the proportion of tumors showing extrarenal spread with increasing size, ranging from 0% for tumors <1 cm in diameter to 84.7% for tumors >6 to 7 cm. The study has shown that for ccRCC, the extrarenal spread of tumor is strongly associated with the size of the primary tumor. The study has also shown that renal sinus invasion and/or perirenal fat infiltration by tumor is commonplace in tumors >7 cm in maximum extent and that tumors of this dimension are rarely organ-confined. These findings provide evidence that the defining features of pT1, pT2, and pT3a staging categories for ccRCC require revision.

The Gleason Grading system has been used for over 50 years to prognosticate and guide the treatment for patients with prostate cancer. At consensus conferences in 2005 and 2014 under the guidance of the International Society of Urological Pathology (ISUP), the system has undergone major modifications to reflect modern diagnostic and therapeutic practices. The 2014 consensus conference yielded recommendations regarding cribriform, mucinous, glomeruloid and intraductal patterns, the most significant of which was the removal of any cribriform pattern from Gleason grade 3. Furthermore, a Gleason score grouping system was endorsed which consisted of five grades where Gleason score 6 (3+3) was classified as grade 1 which better reflected the mostly indolent behaviour of these tumours. Another issue discussed at the meeting and subsequently endorsed was that in Gleason score 7 cases, the percentage pattern 4 should be recorded. This is especially important in situations where modern active surveillance protocols expand to include men with low volume pattern 4. While major progress was made at the conference, several issues were either not resolved or not discussed at all. Most of these items relate to details of assignment of Gleason score and ISUP grade in specific specimen types and grading scenarios. This detailed review looks at the 2014 ISUP conference results and subsequent literature from an international perspective and proposes several recommendations. The specific issues addressed are percentage pattern 4 in Gleason score 7 tumours, percentage patterns 4 and 5 or 4/5 in Gleason score 8-10 disease, minor (≤5%) high grade patterns when either 2 or 3 patterns are present, level of reporting (core, specimen, case), dealing with grade diversity among site (highest and composite scores) and reporting scores in radical prostatectomy specimens with multifocal disease. It is recognised that for many of these issues, a strong evidence base does not exist, and further research studies are required. The proposed recommendations mostly reflect consolidated expert opinion and they are classified as established if there was prior agreement by consensus and provisional if there was no previous agreement or if the item was not discussed at prior consensus conferences. For some items there are reporting options that reflect the local requirements and diverse practice models of the international urological pathology community. The proposed recommendations provide a framework for discussion at future consensus meetings., (Copyright © 2019 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Purpose: Positron emission tomography (PET) for prostate-specific membrane antigen (PSMA) represents a promising method for prostate cancer diagnosis and staging. Comparisons of PSMA-based tumour characterisation to multiparametric MRI (mpMRI) are limited, hence this study sought to compare the diagnostic accuracy of 68 Ga-PSMA PET/CT to mpMRI against radical prostatectomy (RP) whole gland histopathology., Methods: A retrospective cohort study of consecutive patients who underwent pre-operative mpMRI and 68 Ga-PSMA PET/CT followed by a RP was performed. Standard clinical parameters were collected. "Per patient" and "per lesion" analyses for image-based detection according to RP histopathology were described using sensitivity, specificity and other measures of diagnostic accuracy., Results: Fifty-eight patients (median age 65.5 years, median PSA 7.35 ng/mL) underwent RP, resulting in a high-risk cohort (≥pT3 69%). Sensitivities for identification of index lesion, bilateral and multifocal disease were 90%, 21%, 19% for mpMRI and 93%, 42%, 34% for 68 Ga-PSMA PET/CT. Histology analyses revealed 88 cancer foci of Gleason grades 3 + 3 (4%), 3 + 4 (64%), 4 + 3 (19%), 4 + 4 (3%) and ≥ 4 + 5 (10%), of which 68 Ga-PSMA PET/CT correctly detected more foci (78%, AUC 0.817) than mpMRI (69%, AUC 0.729)., Conclusions: 68 Ga-PSMA PET/CT may better reflect RP histopathology compared to mpMRI when considering multifocal and bilateral disease. These findings may influence surgical planning, targeted biopsy and focal therapy strategies and require further research.

Background: Benign prostatic hyperplasia (BPH) is the most common benign tumour in men. Although men with BPH often need medical or surgical management from a urologist at some point throughout the timeline of their disease, most men are initially assessed and managed by a general practitioner (GP) in the primary healthcare setting., Objective: The aim of this article is to highlight the principles of the pathogenesis, presentation, assessment and management of BPH in a primary care setting., Discussion: Between 2009 and 2011, BPH was managed by GPs at approximately 228,000 general practice visits per annum in Australia. Several changes in pharmaceutical agents and surgical intervention have occurred over the past decade. As a result, it is imperative that GPs remain up to date with assessment and management of BPH, are aware of new therapies and understand when to refer to a urologist.

Background: Diagnosis and monitoring of localized prostate cancer requires discovery and validation of noninvasive biomarkers. Nuclear magnetic resonance (NMR)-based metabolomics of seminal plasma reportedly improves diagnostic accuracy, but requires validation in a high-risk clinical cohort., Materials and Methods: Seminal plasma samples of 151 men being investigated for prostate cancer were analyzed with 1 H-NMR spectroscopy. After adjustment for buffer (add-to-subtract) and endogenous enzyme influence on metabolites, metabolite profiling was performed with multivariate statistical analysis (principal components analysis, partial least squares) and targeted quantitation., Results: Seminal plasma metabolites best predicted low- and intermediate-risk prostate cancer with differences observed between these groups and benign samples. Lipids/lipoproteins dominated spectra of high grade samples with less metabolite contributions. Overall prostate cancer prediction using previously described metabolites was not validated., Conclusion: Metabolomics of seminal plasma in vitro may assist urologists with diagnosis and monitoring of either low or intermediate grade prostate cancer. Less clinical benefit may be observed for high-risk patients. Further investigation in active surveillance cohorts, and/or in combination with in vivo magnetic resonance spectroscopic imaging may further optimize localized prostate cancer outcomes.

Objective: To compare the detection rates of prostate cancer (PCa) in men with Prostate Imaging-Reporting and Data System (PI-RADS) 3-5 abnormalities on 3-Tesla multiparametric (mp) magnetic resonance imaging (MRI) using in-bore MRI-guided biopsy compared with cognitively directed transperineal (cTP) biopsy and transrectal ultrasonography (cTRUS) biopsy., Methods: This was a retrospective single-centre study of consecutive men attending the private practice clinic of an experienced urologist performing MRI-guided biopsy and an experienced urologist performing cTP and cTRUS biopsy techniques for PI-RADS 3-5 lesions identified on 3-Tesla mpMRI., Results: There were 595 target mpMRI lesions from 482 men with PI-RADS 3-5 regions of interest during 483 episodes of biopsy. The abnormal mpMRI target lesion was biopsied using the MRI-guided method for 298 biopsies, the cTP method for 248 biopsies and the cTRUS method for 49 biopsies. There were no significant differences in PCa detection among the three biopsy methods in PI-RADS 3 (48.9%, 40.0% and 44.4%, respectively), PI-RADS 4 (73.2%, 81.0% and 85.0%, respectively) or PI-RADS 5 (95.2, 92.0% and 95.0%, respectively) lesions, and there was no significant difference in detection of significant PCa among the biopsy methods in PI-RADS 3 (42.2%, 30.0% and 33.3%, respectively), PI-RADS 4 (66.8%, 66.0% and 80.0%, respectively) or PI-RADS 5 (90.5%, 89.8% and 90.0%, respectively) lesions. There were also no differences in PCa or significant PCa detection based on lesion location or size among the methods., Conclusion: We found no significant difference in the ability to detect PCa or significant PCa using targeted MRI-guided, cTP or cTRUS biopsy methods. Identification of an abnormal area on mpMRI appears to be more important in increasing the detection of PCa than the technique used to biopsy an MRI abnormality., (© 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.)

Background and Objectives: The Göteborg randomised population-based prostate cancer screening trial demonstrated that prostate-specific antigen (PSA)-based screening reduces prostate cancer deaths compared with an age-matched control group. Utilising the prostate cancer detection rates from this study, we investigated the clinical and cost effectiveness of a similar PSA-based screening strategy for an Australian population of men aged 50-69 years., Methods: A decision model that incorporated Markov processes was developed from a health system perspective. The base-case scenario compared a population-based screening programme with current opportunistic screening practices. Costs, utility values, treatment patterns and background mortality rates were derived from Australian data. All costs were adjusted to reflect July 2015 Australian dollars (A$). An alternative scenario compared systematic with opportunistic screening but with optimisation of active surveillance (AS) uptake in both groups. A discount rate of 5 % for costs and benefits was utilised. Univariate and probabilistic sensitivity analyses were performed to assess the effect of variable uncertainty on model outcomes., Results: Our model very closely replicated the number of deaths from both prostate cancer and background mortality in the Göteborg study. The incremental cost per quality-adjusted life-year (QALY) for PSA screening was A$147,528. However, for years of life gained (LYGs), PSA-based screening (A$45,890/LYG) appeared more favourable. Our alternative scenario with optimised AS improved cost utility to A$45,881/QALY, with screening becoming cost effective at a 92 % AS uptake rate. Both modelled scenarios were most sensitive to the utility of patients before and after intervention, and the discount rate used., Conclusion: PSA-based screening is not cost effective compared with Australia's assumed willingness-to-pay threshold of A$50,000/QALY. It appears more cost effective if LYGs are used as the relevant outcome, and is more cost effective than the established Australian breast cancer screening programme on this basis. Optimised utilisation of AS increases the cost effectiveness of prostate cancer screening dramatically.

Introduction: Early localisation of disease recurrence after definitive treatment of prostate cancer is vital to determine suitability for salvage treatment. Our aim was to further investigate the relationship between prostate specific antigen (PSA) level and detection of suspected cancer recurrence using 68  Ga-PSMA PET/CT in patients with biochemical recurrence after radical prostatectomy (RP) or radiotherapy, particularly at low PSA levels., Methods: This retrospective single tertiary referral institution cohort study of men reviewed the results of 68  Ga-PSMA PET/CT scans for investigation of post RP and post radiotherapy PSA recurrence following primary treatment of prostate cancer. We included men with suspected recurrent prostate cancer based on an elevated post treatment PSA level. The data collected analyzed the relationship of the pre-scan PSA level to the probability of a positive scan finding for recurrent prostate cancer., Results: Of the cohort of 532 men, 425 had a previous RP and 107 had prior radiotherapy. The median PSA of the RP group was 0.59 ng/mL and 5.8 ng/mL in the radiotherapy group. In the post RP cohort, the detection rate of 68  Ga-PSMA PET/CT was 11.3% for PSA 0.01 to <0.2 ng/mL, 26.6% for PSA 0.2 to <0.5 ng/mL, 53.3% for PSA 0.5 to <1 ng/mL, 79.1% for PSA 1 to <2 ng/mL and 95.5% for PSA ≥2. Lymph node metastasis post RP was identified in 68% of men with suspected disease recurrence. In the post radiotherapy cohort the detection rate was 33.3% for PSA 0.01 to <0.5 ng/mL, 71.4% for PSA 0.5 to <1 ng/mL, 93.3% for PSA 1 to <2 ng/mL and 100% for PSA ≥2. Local recurrence after radiotherapy was suspected in 71% of the cohort and 40% had suspected lymph node metastasis., Conclusions: To our knowledge, this is largest cohort study of detection rates of 68  Ga-PSMA PET/CT in patients with biochemical recurrence after definitive treatment of prostate cancer, including patients with PSA <0.5 and in a post radiotherapy cohort. Detection of suspected recurrent disease outside the pelvis at low PSA levels will influence the decision for salvage treatment options., (© 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.)

Background: The absence of trial data comparing robot-assisted laparoscopic prostatectomy and open radical retropubic prostatectomy is a crucial knowledge gap in uro-oncology. We aimed to compare these two approaches in terms of functional and oncological outcomes and report the early postoperative outcomes at 12 weeks., Method: In this randomised controlled phase 3 study, men who had newly diagnosed clinically localised prostate cancer and who had chosen surgery as their treatment approach, were able to read and speak English, had no previous history of head injury, dementia, or psychiatric illness or no other concurrent cancer, had an estimated life expectancy of 10 years or more, and were aged between 35 years and 70 years were eligible and recruited from the Royal Brisbane and Women's Hospital (Brisbane, QLD). Participants were randomly assigned (1:1) to receive either robot-assisted laparoscopic prostatectomy or radical retropubic prostatectomy. Randomisation was computer generated and occurred in blocks of ten. This was an open trial; however, study investigators involved in data analysis were masked to each patient's condition. Further, a masked central pathologist reviewed the biopsy and radical prostatectomy specimens. Primary outcomes were urinary function (urinary domain of EPIC) and sexual function (sexual domain of EPIC and IIEF) at 6 weeks, 12 weeks, and 24 months and oncological outcome (positive surgical margin status and biochemical and imaging evidence of progression at 24 months). The trial was powered to assess health-related and domain-specific quality of life outcomes over 24 months. We report here the early outcomes at 6 weeks and 12 weeks. The per-protocol populations were included in the primary and safety analyses. This trial was registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), number ACTRN12611000661976., Findings: Between Aug 23, 2010, and Nov 25, 2014, 326 men were enrolled, of whom 163 were randomly assigned to radical retropubic prostatectomy and 163 to robot-assisted laparoscopic prostatectomy. 18 withdrew (12 assigned to radical retropubic prostatectomy and six assigned to robot-assisted laparoscopic prostatectomy); thus, 151 in the radical retropubic prostatectomy group proceeded to surgery and 157 in the robot-assisted laparoscopic prostatectomy group. 121 assigned to radical retropubic prostatectomy completed the 12 week questionnaire versus 131 assigned to robot-assisted laparoscopic prostatectomy. Urinary function scores did not differ significantly between the radical retropubic prostatectomy group and robot-assisted laparoscopic prostatectomy group at 6 weeks post-surgery (74·50 vs 71·10; p=0·09) or 12 weeks post-surgery (83·80 vs 82·50; p=0·48). Sexual function scores did not differ significantly between the radical retropubic prostatectomy group and robot-assisted laparoscopic prostatectomy group at 6 weeks post-surgery (30·70 vs 32·70; p=0·45) or 12 weeks post-surgery (35·00 vs 38·90; p=0·18). Equivalence testing on the difference between the proportion of positive surgical margins between the two groups (15 [10%] in the radical retropubic prostatectomy group vs 23 [15%] in the robot-assisted laparoscopic prostatectomy group) showed that equality between the two techniques could not be established based on a 90% CI with a Δ of 10%. However, a superiority test showed that the two proportions were not significantly different (p=0·21). 14 patients (9%) in the radical retropubic prostatectomy group versus six (4%) in the robot-assisted laparoscopic prostatectomy group had postoperative complications (p=0·052). 12 (8%) men receiving radical retropubic prostatectomy and three (2%) men receiving robot-assisted laparoscopic prostatectomy experienced intraoperative adverse events., Interpretation: These two techniques yield similar functional outcomes at 12 weeks. Longer term follow-up is needed. In the interim, we encourage patients to choose an experienced surgeon they trust and with whom they have rapport, rather than a specific surgical approach., Funding: Cancer Council Queensland., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Prostate cancer (PCa) diagnosis requires improvement with the aid of more accurate biomarkers. Postejaculate urethral washings (PEUW) could be a physiological equivalent to urine obtained following rectal prostatic massage, the current basis for the prostate cancer antigen 3 (PCA3) test. The aim of this study was to investigate if PEUW contained prostate-based material, evidenced by the presence of prostate specific antigen (PSA), and to evaluate the diagnostic performance of PEUW-based biomarkers., Methods: Male patients referred for elevated serum PSA or abnormal digital rectal examination provided ejaculate and PEUW samples. PSA, PCA3, and β2-microglobulin (β2M) were quantified in ejaculate and PEUW and compared with absolute and clinically significant (according to D'Amico criteria) PCa presence, as determined by biopsies. Diagnostic performance was determined and compared with serum PSA using receiver operating characteristic analysis., Results: From 83 patients who provided PEUW samples, paired analysis with ejaculate samples was possible for 38 patients, while analysis in an unpaired, extended cohort was possible for 62 patients. PSA and PCA3 were detected in PEUW, normalized to β2M, and PCA3:PSA was calculated. In predicting absolute PCa status, PCA3:β2M in ejaculate [area under the curve (AUC) 0.717] and PEUW (AUC 0.569) were insignificantly better than PCA3:PSA (AUC 0.668 and 0.431, respectively) and comparable with serum PSA (AUC 0.617) with similar trends observed for the extended cohort. When considering clinically significant PCa presence, serum PSA in the comparison (AUC 0.640) and extended cohorts (AUC 0.665) was comparable with PCA3: β2M (AUC 0.667) and PCA3:PSA (AUC 0.605) in ejaculate, with lower estimates for PEUW in the comparison (PCA3: β2M AUC 0.496; PCA3:PSA AUC 0.342) and extended (PCA3: β2M AUC 0.497; PCA3:PSA AUC 0.469) cohorts. The statistical analysis was limited by sample size., Conclusion: PEUW contains prostatic material, but has limited diagnostic accuracy when considering cell-derived DNA analysis. PCA3-based markers in ejaculate are comparable to serum PSA and digital rectal examination-urine markers.

The 2005 International Society of Urological Pathology (ISUP) modified Gleason grading system was further amended in 2014 with the establishment of grade groupings (ISUP grading). This study examined the predictive value of ISUP grading, comparing results with recognised prognostic parameters.Of 3700 men undergoing radical prostatectomy (RP) reported at Aquesta Pathology between 2008 and 2013, 2079 also had a positive needle biopsy available for review. We examined the association between needle biopsy 2014 ISUP grade and 2005 modified Gleason score, tumour volume, pathological stage of the subsequent RP tumour, as well as biochemical recurrence-free survival (BRFS). The median age was 62 (range 32-79 years). Median serum prostate specific antigen was 5.9 (range 0.4-69 ng/mL). For needle biopsies, 280 (13.5%), 1031 (49.6%), 366 (17.6%), 77 (3.7%) and 325 (15.6%) were 2014 ISUP grades 1-5, respectively. Needle biopsy 2014 ISUP grade showed a significant association with RP tumour volume (p < 0.001), TNM pT and N stage (p < 0.001) and BRFS (p < 0.001). Multivariate analysis using Cox proportional hazards regression model showed serum prostate specific antigen (PSA) at the time of diagnosis and ISUP grade >2 to be significantly associated with BRFS.This study provides evidence of the prognostic significance of ISUP grading for thin core needle biopsy of prostate.

Background: Determining whether men diagnosed with early prostate cancer (PCa) will live long enough to benefit from interventions with curative intent is difficult. Although validated instruments for predicting patient survival are available, these do not have clinical utility so are not used routinely in practice., Objective: To test the hypothesis that volunteers who provided ejaculate specimens had a high survival rate at 10 and 15 yr and beyond., Design, Setting, and Participants: A total of 290 patients investigated because of high serum prostate-specific antigen donated ejaculate specimens for research between January 1992 and May 2003. The median age at the time of ejaculation was 63.5 yr. 153 of the donors were diagnosed with PCa and followed up to December 31, 2013., Outcome Measurements and Statistical Analysis: Survival outcomes were compared with those for the whole population, as indicated by life expectancy tables up to 20 yr., Results and Limitations: Men in the PCa group had life expectancies comparable with values listed in life expectancy tables for the whole population. Overall, PCa-specific and relative survival were significantly better for men in the non-PCa and PCa groups in comparison with men diagnosed with PCa in Queensland during the same period. Relative survival for those aged 20-49, 50-64, and ≥65 yr was >100% for ejaculate donors and 81.5%, 82.7%, and 65.2%, respectively, for the Queensland Cancer Registry reference at 10 yr. These findings for this highly selected patient cohort support the hypothesis that an ability to provide an ejaculate specimen is associated with a high likelihood of surviving 10-20 yr after donation, whether or not PCa was detected., Conclusion: Life expectancy tables may serve as a quick and simple life expectancy indicator for biopsy patients who donate ejaculate., Patient Summary: Life expectancy tables indicated survival of up to 20 yr for men who provided ejaculate specimens for prostate cancer research., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To examine the relation between socio-demographic and clinical factors, and time from consultation to diagnosis and treatment for men with prostate cancer., Methods: Men diagnosed with prostate cancer (n = 1,064, response rate = 82%) were recruited through participating urologists and hospital outpatient clinics in Queensland, Australia, and completed telephone interviews and self-administered questionnaires. Outcome measures were the diagnostic interval (initial consultation to definitive diagnosis) and treatment interval (definitive diagnosis to start of treatment)., Results: Median time to diagnosis was 73 days (IQR = 41-144) and median treatment interval was 65 days (IQR = 36-107). After adjustment, men were more likely to wait more than 70 days for their definitive diagnosis when they initially presented with symptoms (compared with a general checkup) or did not have private health insurance. For treatment interval, men without private health insurance or who were treated with radiotherapy alone were more likely to wait more than 70 days. Treatment intervals were shorter when men received androgen deprivation therapy combined with radiotherapy., Conclusions: Differences in waiting times for diagnosis and treatment related to access to private hospital care suggest that there are inequities in health-care service provision that are system based.

In recent times, PSA screening and a substantial increase in prostate needle biopsies have not only resulted in detection of minute foci of cancer but have also very likely resulted in increased detection of atypical glandular proliferations. Not uncommonly, there are only a limited number of atypical glands in these biopsies, and these require careful evaluation to enable an accurate diagnosis. We describe diagnostic implications, use of immunohistochemistry, and clinical significance of these lesions. Foci of atypical glands, also labeled atypical small acinar proliferation of uncertain significance, have features suspicious for but not diagnostic of cancer. Atypical foci include a broad group of lesions of differing clinical significance. These include benign, small acinar proliferations mimicking prostate cancer and atypical glandular proliferations suspicious for carcinoma. Definite diagnosis requires accurate histopathologic assessment and judicious use of immunohistochemistry. Patients with atypical glands on prostate needle biopsy have a high risk for harboring cancer and therefore have an increased risk for having cancer detected in subsequent biopsies.