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Suppl Figures 1-8. Supplementary Figure 1. Identification of the PCA3-shRNA2 hairpin. (a). Predicted hairpin of PCA3 RNA2. The bases in red are those identified within the prostate RNA transcriptome. (b). BLAST results of the 98bp fragment derived from PCA3-shRNA2 using 3'RACE, indicates that the sequence is found within PCA3 intron 1. Supplementary figure 2. Expression of PCA3 and PCA3-shRNA2 in cell lines representing prostate cancer (blue and labeled) and other malignancies (red). The expression of the two PCA3 RNAs is shown (normalised to PSA mRNA expression) for each of 22 cell lines. The non-prostate cancer cell lines are not labeled for clarity. In order of PCA3-shRNA2 expression these are (from HCT-116 (PCA3-shRNA2 DCt=-15.85), HEK 293, A549, NCI-H460, WM793, RT112, T47D, MRC5, AN3CA, RT4, SKOV-3, EJ, MCF-7, Jurkat and HeLa (PCA3-shRNA2 DCt=5.08)). Supplementary figure 3. Androgen regulated expression of PSA, PCA3 and PCA3 shRNA2. Expression (fold change) was determined using qrtPCR and normalized to a non-androgen regulated U1 RNA. PCA3 and PCA3 shRNA expression was directly related to testosterone concentration within growth media (0, 1nM and 10nM) Supplementary figure 4. Expression of PCA3, BMCC1, PCA3-shRNA2a and PCA3-shRNA2b in malignant and benign prostatic tissue. Significantly higher expression is seen in malignant tissues, when compared to benign tissues, for BMCC1 (DCt: -11.5{plus minus}2 vs. -14.1{plus minus}3, T Test p

Background: PCA3 is a long noncoding RNA (lncRNA) with unknown function, upregulated in prostate cancer. LncRNAs may be processed into smaller active species. We hypothesized this for PCA3.Methods: We computed feasible RNA hairpins within the BMCC1 gene (encompassing PCA3) and searched a prostate transcriptome for these. We measured expression using qRT-PCR in three cohorts of prostate cancer tissues (n = 60), exfoliated urinary cells (n = 484 with cancer and n = 166 controls), and in cell lines (n = 22). We used in silico predictions and RNA knockup to identify potential mRNA targets of short transcribed RNAs.Results: We predicted 13 hairpins, of which PCA3-shRNA2 was most abundant within the prostate transcriptome. PCA3-shRNA2 is located within intron 1 of PCA3 and appears regulated by androgens. Expression of PCA3-shRNA2 was upregulated in malignant prostatic tissues, exfoliated urinary cells from men with prostate cancer (13–273 fold change; t test P < 0.003), and closely correlated to PCA3 expression (r = 0.84–0.93; P < 0.001). Urinary PCA3-shRNA2 (C-index, 0.75–0.81) and PCA3 (C-index, 0.78) could predict the presence of cancer in most men. PCA3-shRNA2 knockup altered the expression of predicted target mRNAs, including COPS2, SOX11, WDR48, TEAD1, and Noggin. PCA3-shRNA2 expression was negatively correlated with COPS2 in patient samples (r = −0.32; P < 0.001).Conclusion: We identified a short RNA within PCA3, whose expression is correlated to PCA3, which may target mRNAs implicated in prostate biology.Impact: This short RNA is stable ex vivo, suggesting a role as a robust biomarker. We identify cytoplasmic enrichment of this RNA and potential targeting of mRNAs implicated in prostate carcinogenesis. Cancer Epidemiol Biomarkers Prev; 24(1); 268–75. ©2014 AACR.

Suppl. Tables 1-3. Supplementary table 1. Predicted hairpin RNAs within PCA3 and BMCC1. Supplementary table 2. Predicted mRNA targets for PCA3-shRNA2. Supplementary table 3. Primers and condition used to detect target mRNAs.

To examine the long-term oncological outcomes and urological morbidity of low-dose-rate prostate brachytherapy (LDRBT) monotherapy using live intraoperative dosimetry planning and an automated needle navigation delivery system for the treatment of men with low and intermediate-risk prostate cancer.A prospective database of 400 consecutive patients who underwent LDRBT between July 2003 and June 2015 was retrospectively reviewed to assess urinary side-effects and biochemical progression, based on the Phoenix definition and also a definition of a prostate-specific antigen (PSA) level of ≥0.2 μg/L.Minimum patient follow-up was 5.5 years. The median follow-up of the entire cohort was 11.8 years. The median (range) PSA level was 6.1 (0.9-17) μg/L and the median Gleason score was 3 + 4. The biochemical relapse-free survival (RFS; freedom from biochemical recurrence) based on the Phoenix definition was 85.8% (343/400). The RFS using a 'surgical' definition of a PSA level of0.2 μg/L was 71% (284/400). Of the 297 men followed for ≥10 years, prostate cancer-specific survival (PCSS) was 98% (291/297). Post-LDRBT urethral stricture developed in 11 men (2.8%, 11/400). For men with ≥10 years of follow-up, 22 men (7.4%, 22/297) required a pad for either stress or urge urinary incontinence (UI). UI was identified in only 2.2% (one of 46) of men who had a bladder neck incision (BNI) before LDRBT.LDRBT is associated with excellent PCSS, with a median follow-up of 11.8 years. The risk of post-implantation urethral stricture and UI is low and a pre-implantation BNI for management of bladder outflow obstruction does not increase the risk of UI or urethral stricture.

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. 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. 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

68Ga prostate specific membrane antigen PET/CT (68Ga-PSMA PET/CT) may be superior to multiparametric MRI (mpMRI) for localisation of prostate cancer tumour foci, however the concordance and differences between 68Ga-PSMA PET/CT and mpMRI when applied to all biopsied patients and potential benefit in patients with negative mpMRI is unclear. Retrospective analysis of patients undergoing mpMRI, prostate biopsy and 68Ga-PSMA PET/CT over a 3-year period. Diagnostic performance of 68Ga-PSMA PET/CT and mpMRI were assessed using biopsy histopathology for the entire cohort and radical prostatectomy specimen in a subset of patients. Lesion concordance and additional detection of each modality were determined, including in a dedicated cohort of patients with mpMRI PIRADS 2 scans. A total of 144 patients were included in the study. Index lesion/foci detection was similar between 68Ga-PSMA PET/CT and mpMRI (sensitivity 83.1% vs 90.1%; p = 0.267), however lesions missed by mpMRI were larger (1.66 cm3 vs 0.72 cm3; p = 0.034). Lesion detection rates were similar across the biopsy histopathology and radical prostatectomy specimen subset, with a high concordance for index (80.1%) and a moderate concordance for total (67%) lesions between the 2 imaging modalities. The additional detection yield favoured 68Ga-PSMA PET/CT over mpMRI for index (13.5% vs 4.3%) and total (18.2% vs 5.4%) lesions; both modalities missed 2.1% and 12.3% of index and total lesions, respectively. 68Ga-PSMA PET/CT identified 9 of 11 patients with PIRADS 2 mpMRI but subsequently diagnosed with Gleason ≥ 3 + 4 disease. Despite high concordance rates, 68Ga-PSMA PET/CT incrementally improved tumour localisation compared with mpMRI. These results suggest that 68Ga-PSMA PET/CT may have an incremental value to that of mpMRI in the diagnostic process for prostate.

© 2019 John Wiley & Sons, Ltd. Background: Men treated for prostate cancer experience heightened psychological distress and have an increased risk of suicide. Management of this distress and risk is crucial for quality urological care. Objective: To identify risk indicators for poorer trajectories of psychological adjustment and health-related quality of life (QoL) after surgery for localised prostate cancer. Design, Setting, and Participants: Patients were newly diagnosed with localised prostate cancer scheduled for surgical treatment. Patients were assessed at baseline (pre-surgery) and 6 weeks, 3 months, 6 months, 12 months, and 24 months post–surgery. Measurements: Assessment measures included sociodemographics, domain-specific and health-related QoL, and psychological distress. Mixed effects regression models were used to analyse the data. Results and Limitations: A total of 233 patients provided data for this analysis (Mage = 60 years, standard deviation [SD] = 4.02; MPSA = 7.37 ng/mL). At baseline, the prevalence of high psychological distress was 28% reducing to 21% at 24 months. Before treatment, younger age, more comorbidities, and worse bowel function were related to greater psychological distress; and younger age and better urinary, sexual, and bowel function were related to better health-related QoL. By contrast, for changes over time, only bowel function was important with better bowel function predicting decreasing psychological distress for men. Conclusions: Regular distress screening is indicated over the 24 months after surgery for localised prostate cancer. Care pathways for men with prostate cancer need also to respond to age-specific concerns and health problems associated with comorbidities in aging men. Focussed symptom control for bowel bother should be a priority.

The Elevation sensitive Oblique Incidence Sounder Experiment (ELOISE) was an extensive experiment undertaken by the Defence Science and Technology (DST) Group that focused on collecting ionospheric sensor data from multiple overlapping ionospheric paths in the Australian region in order to improve understanding of the characteristics of ionospheric variability and its effect on HF radio propagation. The experiment ran from July to October 2015 and included a period of three weeks of increased sample density and three days of dedicated over-the-horizon (OTH) radar operations. It was anticipated that ELOISE would sample a wide range of environmental conditions and present an opportunity to characterise periods of “normal variability” and periods of “exceptional variability” in the ionosphere. This report is a general description of the aims of this experiment and the types of data collected. Particular interest focused on observing and measuring variability in ionospheric electron density gradients and their effect on oblique HF propagation. To this end, ELOISE established a pair of two dimensional HF receiver arrays to directly measure the oblique angle of arrival (AoA) on many overlapping oblique paths. ELOISE also established a dense sub-network of spatially separated quasi-vertical incidence soundings in the vicinity of Alice Springs in central Australia. This enabled a comparison of gradients observed in a dense network of vertical sounders with gradient effects observed in oblique propagation passing overhead. Several additional ionospheric observing systems were also used to give complementary pictures of the fine scale characteristics of ionospheric variability in the region. Plain Language Summary This paper is an overview of the 2015 Elevation sensitive Oblique Incidence Sounder Experiment (ELOISE), an experiment designed to observe and characterise mid-latitude ionospheric disturbances in the Australian region and understand their impact on high frequency (HF) signal propagation. ELOISE involved the simultaneous operation of a large collection of ionospheric sounders enabling ionospheric variability to be characterised on a finely sampled large scale. Particular efforts were made to provide direct high fidelity measurements of the angle of arrival (AoA) on many oblique HF propagation paths. These direct AoA measurements imply horizontal electron density gradients that can be compared to ionospheric gradients estimated from conventional models of the ionosphere derived from the spatial network of sounder sites. The size and scope of the experiment are detailed in this paper and some preliminary results are presented.

To reduce unnecessary prostate biopsies (Pbx), better discrimination is needed. To identify clinically significant prostate cancer (CSPC) we determined the performance of LacdiNAc‐glycosylated prostate‐specific antigen (LDN‐PSA) and LDN‐PSA normalized by prostate volume (LDN‐PSAD). We retrospectively measured LDN‐PSA, total PSA (tPSA), and free PSA/tPSA (F/T PSA) values in 718 men who underwent a Pbx in 3 academic urology clinics in Japan and Canada (Pbx cohort) and in 174 PC patients who subsequently underwent radical prostatectomy in Australia (preop‐PSA cohort). The assays were evaluated using the area under the receiver operating characteristics curve (AUC) and decision curve analyses to discriminate CSPC. In the Pbx cohort, LDN‐PSAD (AUC 0.860) provided significantly better clinical performance for discriminating CSPC compared with LDN‐PSA (AUC 0.827, P = 0.0024), PSAD (AUC 0.809, P

Multiparametric magnetic resonance imaging (mpMRI) improves clinically significant prostate cancer (csPCa) detection by facilitating targeted biopsy (cognitive, fusion technology, or in-gantry MRI guidance) and reducing negative biopsies. This study sought to describe the feasibility of introducing an mpMRI-based triage pathway, including diagnostic performance, applicability to training, and cost analysis. An observational retrospective cohort study of consecutive patients attending a large public tertiary referral training hospital who underwent mpMRI for suspicion of prostate cancer was considered. Standard clinical, MRI-related, histopathological, and financial parameters were collected for analysis of biopsy avoidance, diagnostic accuracy of biopsy approach, and operator (consultant and resident/registrar) and logistical (including financial) feasibility. 653 men underwent mpMRI, of which 344 underwent prostate biopsy resulting in a 47% biopsy avoidance rate. Overall, 240 (69.8%) patients were diagnosed with PCa, of which 208 (60.5%) were clinically significant, with higher rates of csPCa observed for higher PIRADS scores. In patients who underwent both systematic and targeted biopsy (stTPB), targeted cores detected csPCa in 12.7% and 16.6% in more men than systematic cores in PIRADS 5 and 4, respectively, whereas systematic cores detected csPCa in 5% and 3.2% of patients, where targeted cores did not. A high standard of performance was maintained across the study period and the approach was shown to be cost effective. Introdution of an mpMRI-based triage system into a large public tertiary teaching hospital is feasible, cost effective and leads to high rates of prostate cancer diagnosis while reducing unnecessary biopsies and detection of insignificant PCa.

Physical exercise is increasingly recognized as a valuable treatment strategy in managing prostate cancer, not only enhancing supportive care but potentially influencing disease outcomes. However, there are limited studies investigating mechanisms of the tumor-suppressive effect of exercise. Recently, extracellular vesicles (EVs) have been recognized as a therapeutic target for cancer as tumor-derived EVs have the potential to promote metastatic capacity by transferring oncogenic proteins, integrins, and microRNAs to other cells and EVs are also involved in developing drug resistance. Skeletal muscle has been identified as an endocrine organ, releasing EVs into the circulation, and levels of EV-containing factors have been shown to increase in response to exercise. Moreover, preclinical studies have demonstrated the tumor-suppressive effect of protein and microRNA contents in skeletal muscle-derived EVs in various cancers, including prostate cancer. Here we review current knowledge of the tumor-derived EVs in prostate cancer progression and metastasis, the role of exercise in skeletal muscle-derived EVs circulating levels and the alteration of their contents, and the potential tumor-suppressive effect of skeletal muscle-derived EV contents in prostate cancer. In addition, we review the proposed mechanism of exercise in the uptake of skeletal muscle-derived EVs in prostate cancer.

Background Caveolae proteins play diverse roles in cancer development and progression. In prostate cancer, non‐caveolar caveolin‐1 (CAV1) promotes metastasis, while CAVIN1 attenuates CAV1‐induced metastasis. Here, we unveil a novel mechanism linking CAV1 to selective loading of exosomes with metastasis‐promoting microRNAs. Results We identify hnRNPK as a CAV1‐regulated microRNA binding protein. In the absence of CAVIN1, non‐caveolar CAV1 drives localisation of hnRPNK to multi‐vesicular bodies (MVBs), recruiting AsUGnA motif‐containing miRNAs and causing their release within exosomes. This process is dependent on the lipid environment of membranes as shown by cholesterol depletion using methyl‐β‐cyclodextrin or by treatment with n‐3 polyunsaturated fatty acids. Consistent with a role in bone metastasis, knockdown of hnRNPK in prostate cancer PC3 cells abolished the ability of PC3 extracellular vesicles (EV) to induce osteoclastogenesis, and biofluid EV hnRNPK is elevated in metastatic prostate and colorectal cancer. Conclusions Taken together, these results support a novel pan‐cancer mechanism for CAV1‐driven exosomal release of hnRNPK and associated miRNA in metastasis, which is modulated by the membrane lipid environment., Highlights 1. Non‐caveolar caveolin‐1 drives non‐canonical localization of hnRNPK to multivesicular bodies (MVB) via membrane raft‐dependent mechanism. 2. MVB localized hnRNPK mediates EV loading of AsUGnA motif‐containing miRNA, which is required for EV‐induced in vitro osteoclastogenesiss. 3. Elevated EV hnRNPK in biofluids from metastatic cancer patients suggest a role as a biomarker.

IntroductionActive surveillance (AS) for patients with prostate cancer (PC) with low risk of PC death is an alternative to radical treatment. A major drawback of AS is the uncertainty whether a patient truly has low risk PC based on biopsy alone. Multiparametric MRI scan together with biopsy, appears useful in separating patients who need curative therapy from those for whom AS may be safe. Two small clinical trials have shown short-term high-dose vitamin D supplementation may prevent PC progression. There is no substantial evidence for its long-term safety and efficacy, hence its use in the care of men with PC on AS needs assessment. This protocol describes the ProsD clinical trial which aims to determine if oral high-dose vitamin D supplementation taken monthly for 2 years can prevent PC progression in cases with low-to-intermediate risk of progression.Method and analysisThis is an Australian national multicentre, 2:1 double-blinded placebo-controlled phase II randomised controlled trial of monthly oral high-dose vitamin D supplementation (50 000 IU cholecalciferol), in men diagnosed with localised PC who have low-to-intermediate risk of disease progression and are being managed by AS. This trial will assess the feasibility, efficacy and safety of supplementing men with an initial oral loading dose of 500 000 IU cholecalciferol, followed by a monthly oral dose of 50 000 IU during the 24 months of AS. The primary trial outcome is the commencement of active therapy for clinical or non-clinical reason, within 2 years of AS.Ethics and disseminationThis trial is approved by Bellberry Ethics Committee (2016-06-459). All results will be reported in peer-reviewed journals.Trial registration numberACTRN12616001707459.

Background Active surveillance (AS) is the disease management option of choice for low-risk prostate cancer. Despite this, men with low-risk prostate cancer (LRPC) find management decisions distressing and confusing. We developed Navigate, an online decision aid to help men and their partners make management decisions consistent with their values. The aims are to evaluate the impact of Navigate on uptake of AS; decision-making preparedness; decisional conflict, regret and satisfaction; quality of illness communication; and prostate cancer-specific quality of life and anxiety. In addition, the healthcare cost impact, cost-effectiveness and patterns of use of Navigate will be assessed. This paper describes the study protocol. Methods Three hundred four men and their partners are randomly assigned one-to-one to Navigate or to the control arm. Randomisation is electronically generated and stratified by site. Navigate is an online decision aid that presents up-to-date, unbiased information on LRPC tailored to Australian men and their partners including each management option and potential side-effects, and an interactive values clarification exercise. Participants in the control arm will be directed to the website of Australia’s peak national body for prostate cancer. Eligible patients will be men within 3 months of being diagnosed with LRPC, aged 18 years or older, and who are yet to make a treatment decision, who are deemed eligible for AS by their treating clinician and who have Internet access and sufficient English to participate. The primary outcome is self-reported uptake of AS as the first-line management option. Secondary outcomes include self-reported preparedness for decision-making; decisional conflict, regret and satisfaction; quality of illness communication; and prostate cancer-specific quality of life. Uptake of AS 1 month after consent will be determined through patient self-report. Men and their partners will complete study outcome measures before randomisation and 1, 3 and 6 months after study consent. Discussion The Navigate online decision aid has the potential to increase the choice of AS in LRPC, avoiding or delaying unnecessary radical treatments and associated side effects. In addition, Navigate is likely to reduce patients’ and partners’ confusion and distress in management decision-making and increase their quality of life. Trial registration Australian and New Zealand Clinical Trial Registry ACTRN12616001665426. Registered on 2 December 2016. All items from the WHO Trial Registration Data set can be found in this manuscript.

Objectives To assess the long-term effects of various exercise modes on psychological distress in men with prostate cancer on androgen deprivation therapy (ADT). Patients and methods 135 prostate cancer patients aged 43–90 years on ADT were randomized to twice weekly supervised impact loading and resistance exercise (ImpRes), supervised aerobic and resistance exercise (AerRes), and usual care/delayed supervised aerobic exercise (DelAer) for 12 months, and completed measures of psychological distress using the Brief Symptom Inventory-18 (BSI-18). BSI-18 provides three subscales for anxiety, depression, and somatisation, as well as the global severity index (GSI) where higher scores indicate higher distress. Results Following the intervention, somatization was not different to baseline, however, there were significant interactions (p p p p p = 0.031). Men with the highest level of anxiety, depression, somatization, and the GSI improved the most with exercise (ptrend Conclusion Various supervised exercise modes (aerobic, resistance and impact loading) are effective in reducing psychological distress in men with prostate cancer on ADT. Those with the highest level of psychological distress improved the most. Supervised exercise should be prescribed to improve psychological health in prostate cancer patients on ADT.

Vitamin D may reduce mortality from prostate cancer (PC). We examined the associations of post-treatment plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D concentrations with PC mortality. Participants were PC cases from the New South Wales Prostate Cancer Care. All contactable and consenting participants, at 4.9 to 8.6 years after diagnosis, were interviewed and had plasma 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) measured in blood specimens. Cox regression allowing for left-truncation was used to calculate adjusted mortality hazards ratios (HR) and 95% confidence intervals (95% CI) for all-cause and PC-specific mortality in relation to vitamin D levels and other potentially-predictive variables. Of the participants (n = 111; 75·9% response rate), there were 198 deaths from any cause and 41 from PC in the study period. Plasma 25(OH)D was not associated with all-cause or PC-specific mortality (p-values > 0·10). Plasma 1,25(OH)2D was inversely associated with all-cause mortality (HR for highest relative to lowest quartile = 0·45; 95% CI: 0·29–0·69), and PC-specific mortality (HR = 0·40; 95% CI: 0·14–1·19). These associations were apparent only in men with aggressive PC: all-cause mortality HR = 0·28 (95% CI·0·15–0·52; p-interaction = 0·07) and PC-specific mortality HR = 0·26 (95% CI: 0·07–1.00). Time spent outdoors was also associated with lower all-cause (HR for 4th relative to 1st exposure quartile = 0·42; 95% CI: 0·24–0·75) and PC-specific (HR = 0·48; 95% CI: 0·14–1·64) mortality, although the 95% CI for the latter was wide. The inverse association between post-treatment plasma 1,25(OH)2D levels and all-cause and PC-specific mortality in men with aggressive PC, suggest a possible beneficial effect of vitamin D supplementation in these men.

The original version of this Article contained an error in the spelling of the author Manuela Gago-Dominguez, which was incorrectly given as Manuela G. Dominguez. This has now been corrected in both the PDF and HTML versions of the Article.

INTRODUCTION AND OBJECTIVE:To reduce unnecessary prostate biopsies (Pbx), better discrimination is needed. To identify significant prostate cancer (sigPC) we determined the performance of LacdiNAc-...

The aim of this thesis was to develop a technique, using autologous urinary tract tissues, to replace segments of proximal ureters. These studies were undertaken to test the hypothesis that urinary tract in continuity could be used for overcoming the problem of proximal ureteric defects.The sub-aims were:1. To confirm previously reported studies and specifically examine omentum as the supporting vascular structure. 2. To introduce and assess the adaptations of 'intubated neo-ureterotomies' and previously established omental pedicles.3. To incorporate the findings and conclusions from previous studies as complimentary extensions of currently used procedures, yet, in addition, make provision for reliable salvage operations should they be required subsequently.These studies were performed on dogs because of their recognised suitability (Hinman, 1984) and their ready availability. To enable long-term follow-up, the experimental programme took 10 years so that the consequences of these techniques could be appreciated fully.In preliminary studies, the tendency for autologous partial thickness bladder grafts to remain viable as replacements for excised segments of distal ureters was confirmed. In addition, omentum was shown to be very suitable for providing vascular support. The histological changes associated with successful 'grafting' were detailed and the potential for both 2 and 3-stage procedures considered.The next experiments examined free partial thickness grafts which were wrapped with omentum at the time of the procedures. Intubated 'graft neo-ureterotomies' (Davis-type intubations) were adopted in an attempt to improve results but great difficulty was experienced in keeping stents in position for the proscribed time in the protocol of 8 weeks. When a reliable technique for keeping stents in situ was developed, 8 of the 14 dogs studied at 12 months radiologically had acceptable calyceal appearances with intravenous urography (IVU). Urodynamically, 9 of the 14 were unobstructed compared to their contralateral controls. Four of the 5 obstructed upper tracts were due to graft failures.In the next studies, a 3 stage procedure was employed to lessen the likelihood of graft failure. The intubated neo-ureterotomy technique was used as before. At the first operation, a vascular pedicle was established by fixing omentum in a gutter of incised outer bladder wall. This omental pedicle supported the partial thickness bladder graft which was isolated from the bladder at a second procedure, 4 weeks later, to replace a length of excised uppermost ureter. Stents were removed 8 weeks after the second procedure. At 12 months, all but 2 dogs had acceptable calyceal appearances radiologically, and urodynamically none of the upper tracts was obstructed. As in the previous group, grafts did not appear to contract at all, but ureters on either sides of the grafts tended to contract more vigorously than did the contralateral controls. There were no graft failures.The final experiment was designed to implement the principle of a two-stage partial thickness bladder graft with the provision of a graft on a pre-established omental pedicle as a 'guaranteed' retrieval procedure, should this be needed. In addition, the approach devised complements the currently used and popular techniques of Psoas Hitch and Boari Bladder Flap. Of the 10 dogs studied for 6 months after their Bladder Advancement Extension Graft Procedures, none was obstructed at the end of this time, though 2 required retrieval procedures.The Bladder Advancement Extension Graft Technique provides a graft, supported by omentum, longer than the donor site, urothelially lined with viable muscle, which, in addition, successfully bridges the gap between kidney and bladder with provision for a simple corrective procedure for any stenoses which may develop. This approach is a logical and comprehensive extension of current surgical principles and has been developed fully in dogs. It now awaits application and evaluation in humans.

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 68Ga-PSMA PET/CT to mpMRI against radical prostatectomy (RP) whole gland histopathology. A retrospective cohort study of consecutive patients who underwent pre-operative mpMRI and 68Ga-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. 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 68Ga-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 68Ga-PSMA PET/CT correctly detected more foci (78%, AUC 0.817) than mpMRI (69%, AUC 0.729). 68Ga-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.

An Australian network of oblique angle-of-arrival (AoA) ionosondes was installed as part of the ELOISE experimental campaign in September 2015, aimed at an improved understanding of the spatial and temporal structure of traveling ionospheric disturbances (TIDs) at mid-latitudes. In this paper, the array design and signal processing for the AoA sounder is described, along with a sample of results showing typical disturbance signatures. Realistic parameterized models of electron density perturbations, along with geometric ray tracing, were used to synthesize the effects of medium to large scale TIDs on the sounder observables and aid in classifying the measurements.

Objective: Research suggests some men on active surveillance for low risk, localised prostate cancer, will opt for treatment before evidence of disease progression due to anxiety or uncertainty. This study aims to explore the experiences of men (and their partners) on active surveillance, to further understand the perceived benefits, challenges, and facilitators for adherence, in order to inform person‐centred support. Methods: Semi‐structured, qualitative interviews were conducted with participants (13 males currently or previously on active surveillance, 5 female partners) via telephone or face‐to‐face. Interviews were audiotaped, transcribed verbatim, and thematically analysed. Results: The majority of participants described active surveillance in a positive, nonchalant manner. However, some participants described feeling concerned, anxious, or worried before follow‐up appointments, often due to a fear of cancer progression. Despite this, most participants did not desire additional psychological support, as it had already been accessed or was considered unnecessary. Several factors appeared to facilitate their adherence and influence their experience, including their perception of cancer, the doctor‐patient relationship, and the coping strategies they used (e.g., seeking information online and preparing for the future). Conclusions: This study provides an insight into the facilitators, coping strategies, and views of men and partners who adhered to active surveillance (at least until disease progression). Most participants had adequate access to support and experienced few concerns, although fears were often heightened before appointments. The experiences, needs, and attitudes illustrated in this study may be used to develop effective person‐centred support for men on active surveillance at risk to leaving prematurely.

The use of emerging nanotechnologies, such as plasmonic nanoparticles in diagnostic applications, potentially offers opportunities to revolutionize disease management and patient healthcare. Despite worldwide research efforts in this area, there is still a dearth of nanodiagnostics which have been successfully translated for real-world patient usage due to the predominant sole focus on assay analytical performance and lack of detailed investigations into clinical performance in human samples. In a bid to address this pressing need, we herein describe a comprehensive clinical verification of a prospective label-free surface-enhanced Raman scattering (SERS) nanodiagnostic assay for prostate cancer (PCa) risk stratification. This contribution depicts a roadmap of (1) designing a SERS assay for robust and accurate detection of clinically validated PCa RNA targets; (2) employing a relevant and proven PCa clinical biomarker model to test our nanodiagnostic assay; and (3) investigating the clinical performance on independent training ( n = 80) and validation ( n = 40) cohorts of PCa human patient samples. By relating the detection outcomes to gold-standard patient biopsy findings, we established a PCa risk scoring system which exhibited a clinical sensitivity and specificity of 0.87 and 0.90, respectively [area-under-curve of 0.84 (95% confidence interval: 0.81-0.87) for differentiating high- and low-risk PCa] in the validation cohort. We envision that our SERS nanodiagnostic design and clinical verification approach may aid in the individualized prediction of PCa presence and risk stratification and may overall serve as an archetypical strategy to encourage comprehensive clinical evaluation of nanodiagnostic innovations.

Objective: Exercise may reduce morbidity, increase survival, and improve quality of life (QoL) in prostate cancer patients. However, effective ways to encourage exercise outside carefully controlled clinical trials remain uncertain. We evaluated the effectiveness of peer‐led self‐management for increasing exercise participation in men with localized prostate cancer. Methods: Four hundred and sixty‐three prostate cancer patients from Queensland, Australia were randomized to a monthly telephone‐based group peer support for 6 months supported by self‐management materials and exercise equipment (INT, n = 232) or usual care (UC, n = 231). Participants were assessed at baseline, 3, 6, and 12 months. Primary outcomes were compliance with exercise guidelines; secondary outcomes were psychological distress and QoL. Results: Patients in INT engaged in more resistance exercise than UC at 3 months (19.4 [95% CI 6.52 to 32.28] min/wk, P = .003) and 6 months (14.6 [95% CI 1.69 to 27.58] min/wk, P = .027); more men achieved sufficient physical activity levels at 3 months (χ2 = 8.89, P = 0.003). There was no difference between groups for aerobic‐based activity at any time point nor for resistance exercise time at 12‐month follow‐up. INT had higher QoL Relationships scores at 3 months (.03 [95% CI .00 to .06], P = .038) compared with UC. Limitation included self‐reported assessment of exercise. Conclusions: Peer‐led intervention was effective in increasing patients' resistance exercise participation in the short‐to‐medium term and in the number of men achieving sufficient activity levels in the short‐term; however, this was not accompanied by overall improvements in QoL or psychological distress. Methods to increase effectiveness and maintain long‐term adherence require further investigation.

© 2020, Springer-Verlag GmbH Germany, part of Springer Nature. 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.

Objective To estimate costs on the Medicare Benefits Schedule (MBS) and the Pharmaceutical Benefits Scheme (PBS) attributable to the diagnosis and treatment of prostate cancer. Methods We used data from a cohort study of 1064 men with localized prostate cancer recruited between 2005 and 2007 by 24 urologists across 10 sites in Queensland, Australia (ProsCan). We estimated the MBS and PBS costs attributable to prostate cancer from the date of initial appointment to 12 months after diagnosis in 2013 Australian dollars using a comparison group without prostate cancer. We used generalized linear modeling to identify key determinants of higher treatment-related costs. Results From the date of initial appointment to 12 months postdiagnosis, the average MBS costs attributable to prostate cancer were $9,357 (SD $191) per patient. These MBS costs were most sensitive to having private health insurance and the type of primary treatment received. The PBS costs were higher in the control group than in the ProsCan group ($5,641 vs $1,924). Conclusions The costs of treating and managing prostate cancer are high and these result in a substantial financial burden for the Australian MBS. Costs attributable to prostate cancer appear to vary widely based on initial treatment and these are likely to increase with the introduction of more expensive services and pharmaceuticals. There is a pressing need for better prognostic tools to distinguish between indolent and aggressive prostate tumors to reduce potential over treatment and help ease the burden of prostate cancer.

The Asian Prostate Cancer (A-CaP) Study is an Asia-wide initiative that has been developed over the course of 2 years. The study was launched in December 2015 in Tokyo, Japan, and the participating countries and regions engaged in preparations for the study during the course of 2016, including patient registration and creation of databases for the purpose of the study. The Second A-CaP Meeting was held on September 8, 2016 in Seoul, Korea, with the participation of members and collaborators from 12 countries and regions. Under the study, each participating country or region will begin registration of newly diagnosed prostate cancer patients and conduct prognostic investigations. From the data gathered, common research themes will be identified, such as comparisons among Asian countries of background factors in newly diagnosed prostate cancer patients. This is the first Asia-wide study of prostate cancer and has developed from single country research efforts in this field, including in Japan and Korea. At the Second Meeting, participating countries and regions discussed the status of preparations and discussed various issues that are being faced. These issues include technical challenges in creating databases, promoting participation in each country or region, clarifying issues relating to data input, addressing institutional issues such as institutional review board requirements, and the need for dedicated data managers. The meeting was positioned as an opportunity to share information and address outstanding issues prior to the initiation of the study. In addition to A-CaP-specific discussions, a series of special lectures was also delivered as a means of providing international perspectives on the latest developments in prostate cancer and the use of databases and registration studies around the world. (C) 2017 Asian Pacific Prostate Society, Published by Elsevier Korea LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).