Etiology and management of urethral calculi: A systematic review of contemporary series.

Objective: To conduct a systematic literature review on urethral calculi in a contemporary cohort describing etiology, investigation, and management patterns. Methods: A systematic search of MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL) databases was performed. Articles, including case reports and case series on urethral calculi published between January 2000 and December 2019, were included. Full-text manuscripts were reviewed for clinical parameters including symptomatology, etiology, medical history, investigations, treatment, and outcomes. Data were collated and analyzed with univariate methods. Results: Seventy-four publications met inclusion criteria, reporting on 95 cases. Voiding symptoms (41.1%), pain (40.0%), and acute urinary retention (32.6%) were common presenting features. Urethral calculi were most often initially investigated using plain X-ray (63.2%), with almost all radio-opaque (98.3%). Urethral calculi were frequently associated with coexistent bladder or upper urinary tract calculi (16.8%) and underlying urethral pathology (53.7%) including diverticulum (33.7%) or stricture (13.7%). Urethral calculi were most commonly managed with external urethrolithotomy (31.6%), retrograde manipulation (22.1%), and endoscopic in situ lithotripsy (17.9%). Conclusion: This unique systematic review of urethral calculi provided a summary of clinical features and treatment trends with a suggested treatment algorithm. Management in contemporary urological practice should be according to calculus size, shape, anatomical location, and presence of urethral pathology.

Barriers and enablers of active surveillance for prostate cancer: a qualitive study of clinicians.

OBJECTIVES: To identify and explore barriers to, and enablers of, active surveillance (AS) in men with low-risk prostate cancer (LRPCa), as perceived by PCa clinicians. PATIENTS AND METHODS: Urologists and radiation oncologists in Australia and New Zealand were purposively sampled for a cross-section on gender and practice setting (metropolitan/regional; public/private). Using a grounded theory approach, semi-structed interviews were conducted with participants. Interviews were coded independently by two researchers using open, axial, and selective coding. A constant comparative approach was used to analyse data as it was collected. Thematic saturation was reached after 18 interviews, and a detailed model of barriers to, and enablers of, AS for LRPCa, as perceived by clinicians was developed. RESULTS: A model explaining what affects clinician decision making regarding AS in LRPCa emerged. It was underpinned by three broad themes: (i) clinician perception of patients' barriers and enablers; (ii) clinician perception of their own barriers and enablers; and (iii) engagement with healthcare team and resource availability. CONCLUSIONS: Clinicians unanimously agree that AS is an evidence-based approach for managing LRPCa. Despite this many men do not undergo AS for LRPCa, which is due to the interplay of patient and clinician factors, and their interaction with the wider healthcare system. This study identifies strategies to mitigate barriers and enhance enablers, which could increase access to AS by patients with LRPCa.

Development and External Validation of a Novel Nomogram to Predict the Probability of Pelvic Lymph-node Metastases in Prostate Cancer Patients Using Magnetic Resonance Imaging and Molecular Imaging with Prostate-specific Membrane Antigen Positron Emission Tomography.

BACKGROUND: Preoperative assessment of the probability of pelvic lymph-node metastatic disease (pN1) is required to identify patients with prostate cancer (PCa) who are candidates for extended pelvic lymph-node dissection (ePLND). OBJECTIVE: To develop a novel intuitive prognostic nomogram for predicting pathological lymph-node (pN) status in contemporary patients with primary diagnosed localized PCa, using preoperative clinical and histopathological parameters, magnetic resonance imaging (MRI), and prostate-specific membrane antigen (PSMA) positron emission tomography (PET). DESIGN, SETTING, AND PARTICIPANTS: In total, 700 eligible patients who underwent robot-assisted radical prostatectomy and ePLND were included in the model-building cohort. The external validation cohort consisted of 305 surgically treated patients. Logistic regression with backward elimination was used to select variables for the Amsterdam-Brisbane-Sydney nomogram. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Performance of the final model was evaluated using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision-curve analyses. Models were subsequently validated in an external population. RESULTS AND LIMITATIONS: The Amsterdam-Brisbane-Sydney nomogram included initial prostate-specific antigen value, MRI T stage, highest biopsy grade group (GG), biopsy technique, percentage of systematic cores with clinically significant PCa (GG ≥2), and lymph-node status on PSMA-PET. The AUC for predicting pN status was 0.81 (95% confidence interval [CI] 0.78-0.85) for the final model. On external validation, the Amsterdam-Brisbane-Sydney nomogram showed superior discriminative ability to the Briganti-2017 and Memorial Sloan Kettering Cancer Center (MSKCC) nomograms (AUC 0.75 [95% CI 0.69-0.81] vs 0.67 [95% CI 0.61-0.74] and 0.65 [95% CI 0.58-0.72], respectively; p < 0.05), and similar discriminative ability to the Briganti-2019 nomogram (AUC 0.78 [95% CI 0.71-0.86] vs 0.80 [95% CI 0.73-0.86]; p = 0.76). The Amsterdam-Brisbane-Sydney nomogram showed excellent calibration on external validation, with an increased net benefit at a threshold probability of ≥4%. CONCLUSIONS: The validated Amsterdam-Brisbane-Sydney nomogram performs superior to the Briganti-2017 and MSKCC nomograms, and similar to the Briganti-2019 nomogram. Furthermore, it is applicable in all patients with newly diagnosed unfavorable intermediate- and high-risk PCa. PATIENT SUMMARY: We developed and validated the Amsterdam-Brisbane-Sydney nomogram for the prediction of prostate cancer spread to lymph nodes before surgery. This nomogram performs similar or superior to all presently available nomograms.

Sorting nexin 10 sustains PDGF receptor signaling in glioblastoma stem cells via endosomal protein sorting.

Glioblastoma is the most malignant primary brain tumor, the prognosis of which remains dismal even with aggressive surgical, medical, and radiation therapies. Glioblastoma stem cells (GSCs) promote therapeutic resistance and cellular heterogeneity due to their self-renewal properties and capacity for plasticity. To understand the molecular processes essential for maintaining GSCs, we performed an integrative analysis comparing active enhancer landscapes, transcriptional profiles, and functional genomics profiles of GSCs and non-neoplastic neural stem cells (NSCs). We identified sorting nexin 10 (SNX10), an endosomal protein sorting factor, as selectively expressed in GSCs compared with NSCs and essential for GSC survival. Targeting SNX10 impaired GSC viability and proliferation, induced apoptosis, and reduced self-renewal capacity. Mechanistically, GSCs utilized endosomal protein sorting to promote platelet-derived growth factor receptor ß (PDGFRß) proliferative and stem cell signaling pathways through posttranscriptional regulation of the PDGFR tyrosine kinase. Targeting SNX10 expression extended survival of orthotopic xenograft-bearing mice, and high SNX10 expression correlated with poor glioblastoma patient prognosis, suggesting its potential clinical importance. Thus, our study reveals an essential connection between endosomal protein sorting and oncogenic receptor tyrosine kinase signaling and suggests that targeting endosomal sorting may represent a promising therapeutic approach for glioblastoma treatment.

Modern Active Surveillance in Prostate Cancer: A Narrative Review.

The use of PSA screening has led to downstaging and downgrading of prostate cancer at diagnosis, increasing detection of indolent disease. Active surveillance aims to reduce over-treatment by delaying or avoiding radical treatment and its associated morbidity. However, there is not a consensus on the selection criteria and monitoring schedules that should be used. This article aims to summarize the evidence supporting the safety of active surveillance, the current selection criteria recommended and in use, the incidence of active surveillance, barriers existing to its uptake and future developments in patient selection.

Protocol for mixed-method systematic review of urology in medical school education.

INTRODUCTION: Throughout clinical practice, most doctors will encounter patients with urological conditions. Inclusion of urological topics within medical school curriculums is important to allow doctors to effectively diagnose and manage these conditions, independently and with support from urologists. Awareness of urological education interventions and their effectiveness is essential for improving the quality and outcomes of medical student education. No systematic review of medical school education interventions on urological topics has previously been conducted. This mixed-method systematic review will assess the effectiveness of medical school education interventions on urological topics. METHODS AND ANALYSIS: This mixed-methods systematic review will include qualitative and quantitative studies involving education interventions or practices regarding urological topics conducted within a medical school curriculum. Studies regarding other curriculums including premedical education, junior doctor prevocational education or vocational urological training will be excluded. A search of CINAHL, ERIC, EMBASE, MEDLINE will be conducted for studies published since the year 2001. Dual independent screening of titles and abstracts prior to full text review will be undertaken for all identified results during the initial searches. Any disagreement will be settled by a third reviewer. A convergent segregated approach will be used to synthesise qualitative and quantitative data independently, with the results juxtaposed to identify shared and divergent findings between study types. ETHICS AND DISSEMINATION: No ethical approval was required for this review. Findings from this review will be disseminated via publication, reports and conference presentations.

Xanthogranulomatous orchitis: A rare case of testicular mass.

Xanthogranulomatous orchitis is a rare non-malignant condition. This study reports a new case of xanthogranulomatous orchitis in a 77-year-old male, who presented with acute right scrotal mass. Ultrasound and computed tomography showed a heterogenous lesion involving the testis, with a loculated collection in the overlying scrotal wall. Scrotal exploration revealed an abscess involving the scrotal skin, with hard mass involving the testis, with histological evidence of infiltration and replacement of most testicular parenchyma. This case highlights this important consideration for xanthogranulomatous orchitis in the differential of testicular mass, particularly when associated with a purulent collection. Section headings: •Inflammation and Infection•General Urology.

Mitogenomics and phylogenetics of twelve species of African Saturniidae (Lepidoptera).

African Saturniidae (Lepidoptera) include numerous species consumed at the caterpillar stage throughout the continent, and their importance to local communities as a source of nutrition and seasonal income cannot be overestimated. However, baseline genetic data with utility for the characterization of their diversity, phylogeography and phylogenetic relationships have remained scarce compared to their Asian counterparts. To bridge this gap, we sequenced the mitochondrial genomes of 12 species found in southern Africa for comparative mitogenomics and phylogenetic reconstruction of the family, including the first representatives of the tribes Eochroini and Micragonini. Mitochondrial gene content and organization were conserved across all Saturniidae included in the analyses. The phylogenetic positions of the 12 species were assessed in the context of publicly available mitogenomes using Bayesian inference and maximum likelihood (ML) methods. The monophyly of the tribes Saturniini, Attacini, Bunaeini and Micragonini, the sister relationship between Saturniini and Attacini, and the placement of Eochroa trimenii and Rhodinia fugax in the tribes Eochroini and Attacini, respectively, were strongly supported. These results contribute to significantly expanding genetic data available for African Saturniidae and allow for the development of new mitochondrial markers in future studies.

Bladder cancer in Aboriginal and Torres Strait Islander people living in Australia: a scoping review protocol.

INTRODUCTION: Bladder cancer is the third most common urological malignancy affecting Australians, with key modifiable risk factors. Aboriginal and Torres Strait Islander people suffer from a higher prevalence of cancer-modifiable risk factors, are diagnosed with bladder cancer at a younger age, and have poorer survival rates compared with the general population. A comprehensive overview of the state of current knowledge on bladder cancer in this population is required. METHODS AND ANALYSIS: A search of MEDLINE, CINAHL, EMBASE and Web of Science databases, along with appropriate grey literature sources will be conducted between the 1 April 2022 and 30 April 2022. The reference lists of all included studies will be reviewed for additional appropriate sources. The national bladder cancer dataset compiled by the Australian Institute of Health and Welfare will also be included as a source. All relevant sources meeting inclusion criteria, published in English, from inception onwards will be included. Dual independent screening of titles and abstracts prior to full-text review will be undertaken for all identified results during the initial searches. Preliminary findings will be reviewed with stakeholders, to seek culturally appropriate feedback on the implications of the results. Results will be reported in tabular form, accompanied by a narrative synthesis with comparisons to the wider bladder cancer population. ETHICS AND DISSEMINATION: Ethics review will not be required, as only publicly available data will be analysed. Findings from the scoping review will be published in a peer-reviewed journal and presented at scientific meetings to stakeholders.

Primary tumour PSMA intensity is an independent prognostic biomarker for biochemical recurrence-free survival following radical prostatectomy.

PURPOSE: The prognostic value of PSMA intensity on PSMA PET/CT due to underlying biology and subsequent clinical implications is an emerging topic of interest. We sought to investigate whether primary tumour PSMA PET intensity contributes to pre- and post-operative prediction of oncological outcomes following radical prostatectomy. METHODS: We performed a retrospective cohort study of 848 men who underwent all of multiparametric MRI (mpMRI), transperineal prostate biopsy, and 68 Ga-PSMA PET/CT prior to radical prostatectomy. PSMA intensity, quantified as maximum standard uptake value (SUVmax), and other clinical variables were considered relative to post-operative biochemical recurrence-free survival (BRFS) using Cox regression and Kaplan-Meier analysis. RESULTS: After a median follow-up of 41 months, 219 events occurred; the estimated 3-year BRFS was 79% and the 5-year BRFS was 70%. Increasing PSMA intensity was associated with less favourable BRFS overall (Log rank p < 0.001), and within subgroups of Gleason score category (Log rank p < 0.03). PSMA intensity was significantly associated with shorter time to biochemical recurrence, after adjusting for pre-operative (HR per 5-unit SUVmax increase = 1.15) and post-operative (HR per 5-unit SUVmax increase = 1.10) parameters. CONCLUSION: These results in a large series of patients confirm PSMA intensity to be a novel, independent prognostic factor for BRFS.

Urothelial Carcinoma and Prostate-specific Membrane Antigen: Cellular, Imaging, and Prognostic Implications.

CONTEXT: Staging, restaging, and surveillance of urothelial carcinoma (UC) is challenging due to suboptimal accuracy of standard of care imaging modalities. Prostate-specific membrane antigen (PSMA) imaging may serve to improve characterisation of UC. OBJECTIVE: To appraise available literature regarding cellular, imaging, and prognostic implications of PSMA for UC. EVIDENCE ACQUISITION: A systematic review was performed considering all available literature (including conference abstracts) published from 1990 to 2020 and reported according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines following registration in PROSPERO (CRD42020186744). All relevant texts relating to immunohistochemical analysis and PSMA-based imaging in UC were included and collated. Additionally, FOLH1 (gene encoding PSMA) expression according to The Cancer Genome Atlas (TCGA) database was analysed as well as according to consensus and TCGA molecular classification subtypes and subsequently compared with clinical outcomes. EVIDENCE SYNTHESIS: PSMA expression across UC tumour tissue was heterogeneous (0-100%) but appeared to decrease with increased grade and stage. The TCGA analysis demonstrated loss of FOLH1 expression with increasing T stage (p = 0.0180) and N stage (p = 0.0269), and reduced FOLH1 expression was associated with worse disease-free survival. PSMA expression in UC neovasculature was variable but mostly increased (44-100%). Eleven reports of PSMA-based imaging for UC were identified, reporting on 18 patients. PSMA positron emission tomography (PET) imaging was positive in 17 out of 18 patients. The included literature review data were limited by mostly low-quality, retrospective studies. CONCLUSIONS: Tissue PSMA, or FOLH1 expression, may inversely be associated with pathological and survival outcomes in localised UC. PSMA PET imaging may improve detection of metastatic disease and response to systemic therapy due to PSMA expression in neovasculature. Available evidence is limited; thus, larger, prospective studies are required to confirm early results and define populations that benefit most. PATIENT SUMMARY: In this systematic review, we assess the potential role of prostate-specific membrane antigen in urothelial cancer. We found that its utility is in expression of blood vessels surrounding metastasis. We conclude that it may be beneficial in detecting metastasis and response to systemic therapies.

Lichen sclerosus presenting as an isolated bulbar urethral stricture.

Lichen sclerosus (LS) is a chronic inflammatory condition of the anogenital skin that can cause significant urinary and sexual dysfunction in men, particularly by means of destructive urethral disease. LS is traditionally thought to progress from the meatus with migration along the urethra proximally, however we present a case describing an isolated bulbar urethral stricture secondary to LS. To our knowledge, this has only been reported in the literature in one previous study. Clinician recognition of LS as a potential cause of isolated bulbar urethral stricture disease is important as this has ramifications on follow up and successful management.

Real-time imaging of cellular forces using optical interference.

Important dynamic processes in mechanobiology remain elusive due to a lack of tools to image the small cellular forces at play with sufficient speed and throughput. Here, we introduce a fast, interference-based force imaging method that uses the illumination of an elastic deformable microcavity with two rapidly alternating wavelengths to map forces. We show real-time acquisition and processing of data, obtain images of mechanical activity while scanning across a cell culture, and investigate sub-second fluctuations of the piconewton forces exerted by macrophage podosomes. We also demonstrate force imaging of beating neonatal cardiomyocytes at 100 fps which reveals mechanical aspects of spontaneous oscillatory contraction waves in between the main contraction cycles. These examples illustrate the wider potential of our technique for monitoring cellular forces with high throughput and excellent temporal resolution.

External Validation and Addition of Prostate-specific Membrane Antigen Positron Emission Tomography to the Most Frequently Used Nomograms for the Prediction of Pelvic Lymph-node Metastases: an International Multicenter Study.

BACKGROUND: Different nomograms exist for the preoperative prediction of pelvic lymph-node metastatic disease in individual patients with prostate cancer (PCa). These nomograms do not incorporate modern imaging techniques such as prostate-specific membrane antigen (PSMA) positron emission tomography (PET). OBJECTIVE: To determine the predictive performance of the Briganti 2017, Memorial Sloan Kettering Cancer Center (MSKCC), and Briganti 2019 nomograms with the addition of PSMA-PET in an international, multicenter, present-day cohort of patients undergoing robot-assisted radical prostatectomy (RARP) and extended pelvic lymph-node dissection (ePLND) for localized PCa. DESIGN, SETTING, AND PARTICIPANTS: All 757 eligible patients who underwent a PSMA-PET prior to RARP and ePLND in three reference centers for PCa surgery between January 2016 and November 2020 were included. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Performance of the three nomograms was assessed using the receiver operating characteristic curve-derived area under the curve (AUC), calibration plots, and decision curve analyses. Subsequently, recalibration and addition of PSMA-PET to the nomograms were performed. RESULTS AND LIMITATIONS: Overall, 186/757 patients (25%) had pelvic lymph-node metastatic (pN1) disease on histopathological examination. AUCs of the Briganti 2017, MSKCC, and Briganti 2019 nomograms were 0.70 (95% confidence interval [95% CI]: 0.64-0.77), 0.71 (95% CI: 0.65-0.77), and 0.76 (95% CI: 0.71-0.82), respectively. PSMA-PET findings showed a significant association with pN1 disease when added to the nomograms (p < 0.001). Addition of PSMA-PET substantially improved the discriminative ability of the models yielding cross-validated AUCs of 0.76 (95% CI: 0.70-0.82), 0.77 (95% CI: 0.72-0.83), and 0.82 (95% CI: 0.76-0.87), respectively. In decision curve analyses, the addition of PSMA-PET to the three nomograms resulted in increased net benefits. CONCLUSIONS: The addition of PSMA-PET to the previously developed nomograms showed substantially improved predictive performance, which suggests that PSMA-PET is a likely future candidate for a modern predictive nomogram. PATIENT SUMMARY: Different tools have been developed to individualize the prediction of prostate cancer spread to lymph nodes before surgery. We found that the inclusion of modern imaging (prostate-specific membrane antigen positron emission tomography) improved substantially the overall performance of these prediction tools.

Heavy mineral variations in mid-Carboniferous deltaic sandstones: Records of a pre-depositional sediment history?

Sandstone composition is influenced by multiple factors, including acidic weathering, occurring during storage in the hinterland, prior to deposition. This study aims to better understand and constrain how the nature and duration of such pre-depositional factors might impact the final sediment composition. Mid-Carboniferous deltaic sandstones from the Clare Basin, western Ireland, for which depositional environments and provenance are well constrained, are the target of this study. Conventional heavy mineral analysis and specific heavy mineral ratios, such as the apatite-tourmaline index are utilised to examine these phenomena. Relatively high apatite-tourmaline index values observed in channelised sandstones contrast with lower values seen in sandstones associated with mouth bar and interdistributary bay facies. These variations are not linked to changes in provenance and thus potentially indicate differences in weathering intensity due to variable duration of alluvial storage. These changes are probably linked with shorter hinterland residence time in the channelised than in mouth bar and interdistributary bay sandstones. Variations are seen in the rutile-zircon index without any clear link with facies. These fluctuations could be ascribed to variable supply from a source, which is relatively rich in rutile but poor in zircon and apatite. Despite the apatite component in these sandstones being partially derived from recycled sources, the apatite-tourmaline index stills appears to hold information on the last sedimentary cycle.

European Health Care Systems and the Emerging Influence of European Union Competition Policy.

CONTEXT: Since the 1990s, the EU's influence over national health care policy has been limited to European internal market law or social policy coordination mechanisms. The introduction of EU competition law into health care is more recent and underdeveloped; however, its introduction would potentially be much more far-reaching and disruptive. METHODS: Three EU competition law (state-aid) cases are used and comprise both Court of Justice and European Commission decisions. One is from Ireland, one is from the Netherlands, and the third is from Belgium. FINDINGS: The Belgian (Iris-H) case sees EU institutions scrutinize a clearly "social" (nonmarket) health care model with EU competition law for the first time. This is a highly significant development. It is clear, however, that the European Commission is more reluctant to use EU competition law to scrutinize health care systems than the European courts are. CONCLUSIONS: This intent on the part of EU institutions will have to be assessed in future cases, as considerable uncertainty about its shape and outer contours remains. However, EU competition law, and the EU's state-aid investigation apparatus, encroaching into the national health care systems for the first time is highly significant.

A National Analysis of Temporal Changes in Prescribing of Testosterone Replacement Therapy Considering Methods of Delivery and Government Regulation.

PURPOSE: Testosterone replacement therapy (TRT) is commonly used for various causes of androgen deficiency and subsidized by the Pharmaceutical Benefits Scheme (PBS) in Australia when appropriate. In response to a sharp increase in the prescribing of subsidized TRT, the Australian government instituted new, stricter prescription criteria in April 2015. We aim to demonstrate longitudinal changes in the prescription patterns of subsidized TRT over time. MATERIALS AND METHODS: The publicly available PBS database was accessed for TRT prescription data between 1992-2018. Population estimate data was collected from the Australian Bureau of Statistics for population-adjustment. Data analysis was performed according to class and specific formulation of TRT. Total and population-adjusted trends were considered, as was indexation to 2015 when restrictions were implemented. RESULTS: Longitudinal trends in subsidized TRT prescription demonstrated a progressive overall increase since 2000, according to total prescriptions and population-adjusted estimates, with greater use of topical formulations (gel, patch, cream/spray) and injections. Since 2015, a 37% decline in total population-adjusted prescriptions was observed (1,399-883 per 100,000 persons). Since 2015, relatively increased use of injections (50%) and 1% gel (30%) comprise the majority of contemporary TRT. Annual financial burden due to TRT was $AU16,768 per 100,000 persons prior to 2000 (mean cost 1992-2000), increasing to $AU112,539 in 2018 (due to use of injections). The rate of change in costs slowed after the restrictions were introduced in 2015. CONCLUSIONS: The restrictions in subsidized TRT eligibility enforced by the PBS have reduced overall TRT prescriptions and slowed the cumulative financial burden.

Non-canonical Targets of HIF1a Impair Oligodendrocyte Progenitor Cell Function.

Mammalian cells respond to insufficient oxygen through transcriptional regulators called hypoxia-inducible factors (HIFs). Although transiently protective, prolonged HIF activity drives distinct pathological responses in different tissues. Using a model of chronic HIF1a accumulation in pluripotent-stem-cell-derived oligodendrocyte progenitors (OPCs), we demonstrate that HIF1a activates non-canonical targets to impair generation of oligodendrocytes from OPCs. HIF1a activated a unique set of genes in OPCs through interaction with the OPC-specific transcription factor OLIG2. Non-canonical targets, including Ascl2 and Dlx3, were sufficient to block differentiation through suppression of the oligodendrocyte regulator Sox10. Chemical screening revealed that inhibition of MEK/ERK signaling overcame the HIF1a-mediated block in oligodendrocyte generation by restoring Sox10 expression without affecting canonical HIF1a activity. MEK/ERK inhibition also drove oligodendrocyte formation in hypoxic regions of human oligocortical spheroids. This work defines mechanisms by which HIF1a impairs oligodendrocyte formation and establishes that cell-type-specific HIF1a targets perturb cell function in response to low oxygen.

68Ga-PSMA PET/CT tumour intensity pre-operatively predicts adverse pathological outcomes and progression-free survival in localised prostate cancer.

PURPOSE: Prostate-specific membrane antigen (PSMA) positron emission tomography (PSMA-PET) improves prostate cancer staging. Intraprostatic PSMA intensity may predict clinically relevant oncological outcomes. The aim of this study was to investigate the relationship between intraprostatic PSMA intensity and adverse pathology outcomes, including biochemical progression-free survival (PFS) after radical prostatectomy. METHODS: This is a cohort study of 71 patients with MRI-guided, biopsy-proven prostate cancer and pre-operative 68Ga-PSMA-11 PET/CT prior to radical prostatectomy (RP). Intraprostatic PSMA intensity was correlated to adverse pathology outcomes (Gleason score and upgrading from biopsy, pathological stage) and PFS using multivariate statistical analysis. RESULTS: 68Ga-PSMA-11 PET/CT intensity in vivo predicted all of Gleason score on RP, upgrading from biopsy to RP histopathology, pathological stage, positive surgical margins and PFS. 74.6% (53/71) of patients were free from progression at a median follow-up of 19.5 months (0.4-48 months). Predictive accuracy was particularly enhanced by PSMA among patients with biopsy Gleason score ≤ 3 + 4 (n = 39) as the most significant predictor of PFS according to Cox-proportional hazards regression. Cox-regression adjusted survival analysis predicted a 5.48-fold increase in hazard for Gleason score ≤ 3 + 4 patients with high (SUVmax > 8) compared with low (SUVmax < 8) PSMA intensity. CONCLUSION: Intraprostatic 68Ga-PSMA-11 intensity is prognostic and may be a valuable new biomarker in localised prostate cancer, especially in men with biopsy-proven Gleason 3 + 4 disease considering an initial approach of active surveillance or focal therapy.