The impact of management option on out-of-pocket costs and perceived financial burden among men with localised prostate cancer in Australia within 6 months of diagnosis.

Objective This study aimed to quantify the out-of-pocket (OOP) costs and perceived financial burden among Australian men with localised prostate cancer in the first 6 months after diagnosis, by primary management option. Methods This cost-analysis quantified OOP costs using administrative claims data and self-reported survey data. Financial burden was assessed using the COmprehensive Score for financial Toxicity-Functional Assessment of Chronic Illness Therapy (COST-FACIT) tool. Participants were recruited into a randomised control trial from public or private treatment centres in Victoria and Queensland. Generalised linear models were used to predict OOP costs and COST-FACIT scores. Results Median total OOP costs within 6 months of diagnosis for 256 Australian patients with localised prostate cancer was A$1172 (A$343-2548). Up to 50% of the sample reported A$0 costs for most medical services. Compared with those managed with active surveillance, men having active treatment had 6.4 (95% CI: 3.2-12.7) times greater total OOP costs. Management option, higher Gleason score at diagnosis and having multiple comorbidities were significant predictors of higher OOP costs. Overall high scores on the COST-FACIT indicated low levels of financial burden for the entire sample. Conclusion Largely attributable to being managed with active surveillance, Australian men diagnosed with localised prostate cancer reported relatively low OOP costs and financial burden in the first 6 months post-diagnosis. Together with clinical outcomes, clinicians can use this up to date evidence on costs and perceived financial burdens to assist localised prostate cancer patients and their families make informed decisions about their preferred management option.

Co-designing an online treatment decision aid for men with low-risk prostate cancer: Navigate.

Objectives: To develop an online treatment decision aid (OTDA) to assist patients with low-risk prostate cancer (LRPC) and their partners in making treatment decisions. Patients and methods: Navigate, an OTDA for LRPC, was rigorously co-designed by patients with a confirmed diagnosis or at risk of LRPC and their partners, clinicians, researchers and website designers/developers. A theoretical model guided the development process. A mixed methods approach was used incorporating (1) evidence for essential design elements for OTDAs; (2) evidence for treatment options for LRPC; (3) an iterative co-design process involving stakeholder workshops and prototype review; and (4) expert rating using the International Patient Decision Aid Standards (IPDAS). Three co-design workshops with potential users (n = 12) and research and web-design team members (n = 10) were conducted. Results from each workshop informed OTDA modifications to the OTDA for testing in the subsequent workshop. Clinician (n = 6) and consumer (n = 9) feedback on usability and content on the penultimate version was collected. Results: The initial workshops identified key content and design features that were incorporated into the draft OTDA, re-workshopped and incorporated into the penultimate OTDA. Expert feedback on usability and content was also incorporated into the final OTDA. The final OTDA was deemed comprehensive, clear and appropriate and met all IPDAS criteria. Conclusion: Navigate is an interactive and acceptable OTDA for Australian men with LRPC designed by men for men using a co-design methodology. The effectiveness of Navigate in assisting patient decision-making is currently being assessed in a randomised controlled trial with patients with LRPC and their partners.

Extracellular vesicles for precision medicine in prostate cancer - Is it ready for clinical translation?

Biofluid-based biomarker tests hold great promise for precision medicine in prostate cancer (PCa) clinical practice. Extracellular vesicles (EV) are established as intercellular messengers in cancer development with EV cargos, including protein and nucleic acids, having the potential to serve as biofluid-based biomarkers. Recent clinical studies have begun to evaluate EV-based biomarkers for PCa diagnosis, prognosis, and disease/therapy resistance monitoring. Promising results have led to PCa EV biomarker validation studies which are currently underway with the next challenge being translation to robust clinical assays. However, EV research studies generally use low throughput EV isolation methods and costly molecular profiling technologies that are not suitable for clinical assays. Here, we consider the technical hurdles in translating EV biomarker research findings into precise and cost-effective clinical biomarker assays. Novel microfluidic devices coupling EV extraction with sensitive antibody-based biomarker detection are already being explored for point-of-care applications for rapid provision in personalised medicine approaches.

Oncological and urinary outcomes following low-dose-rate brachytherapy with a median follow-up of 11.8 years.

OBJECTIVES: 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. PATIENTS AND METHODS: 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. RESULTS: 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 of <0.2 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. CONCLUSION: 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.

Potential Role of Exercise Induced Extracellular Vesicles in Prostate Cancer Suppression.

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.

Caveolin-1-driven membrane remodelling regulates hnRNPK-mediated exosomal microRNA sorting in 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-ß-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.

High-dose vitamin D supplementation to prevent prostate cancer progression in localised cases with low-to-intermediate risk of progression on active surveillance (ProsD): protocol of a phase II randomised controlled trial.

INTRODUCTION: Active 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 ANALYSIS: This 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 DISSEMINATION: This trial is approved by Bellberry Ethics Committee (2016-06-459). All results will be reported in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ACTRN12616001707459.

Psychological distress in men with prostate cancer undertaking androgen deprivation therapy: modifying effects of exercise from a year-long randomized controlled trial.

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 < 0.01) for depression, anxiety, and the GSI. In ImpRes, depression was reduced at 12 months compared to baseline and 6 months (0.78 ± 1.39 vs. 1.88 ± 3.24 and 1.48 ± 2.65, p < 0.001), as was the GSI (3.67 ± 4.34 vs. 5.94 ± 7.46 and 4.64 ± 4.73, p < 0.001) with anxiety reduced compared to baseline (1.08 ± 1.54 vs. 1.98 ± 2.56). Depression and the GSI decreased (p < 0.05) in AerRes at 6 months but increased by 12 months, while in DelAer the GSI was reduced at 12 months compared to 6 months (3.78 ± 3.94 vs. 5.25 ± 4.22, p = 0.031). Men with the highest level of anxiety, depression, somatization, and the GSI improved the most with exercise (ptrend < 0.001). 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.

Navigate: a study protocol for a randomised controlled trial of an online treatment decision aid for men with low-risk prostate cancer and their partners.

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.

Transrectal versus transperineal prostate biopsy under intravenous anaesthesia: a clinical, microbiological and cost analysis of 2048 cases over 11 years at a tertiary institution.

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.

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.

Post-treatment levels of plasma 25- and 1,25-dihydroxy vitamin D and mortality in men with aggressive prostate cancer.

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.

Timing of exercise for muscle strength and physical function in men initiating ADT for prostate cancer.

BACKGROUND: Androgen deprivation therapy (ADT) in men with prostate cancer (PCa) results in adverse effects, including reduced muscle strength and physical function, potentially compromising daily functioning. We examined whether it was more efficacious to commence exercise at the onset of ADT rather than later in treatment to counter declines in strength and physical function. METHODS: One-hundred-and-four men with PCa (68.3 ± 7.0 years) initiating ADT were randomised to immediate exercise (IMX, n = 54) or delayed exercise (DEL, n = 50) for 12 months. IMX comprised 6 months of supervised resistance/aerobic/impact exercise initiated at the onset of ADT with a 6-month follow-up. DEL comprised 6 months of usual care followed by 6 months of resistance/aerobic/impact exercise. Upper and lower body muscle strength and physical function were assessed at baseline, 6 and 12 months. RESULTS: There was a significant difference for all strength measures at 6 months favouring IMX (P < 0.001), with net differences in leg press, seated row and chest press strength of 19.9 kg (95% CI, 12.3-27.5 kg), 5.6 kg (3.8-7.4 kg) and 4.3 kg (2.7-5.8 kg), respectively. From 7 to 12 months, DEL increased in all strength measures (P < 0.001), with no differences between groups at 12 months. Similarly, physical function improved (P < 0.001) in IMX compared with DEL at 6 months for the 6-m fast walk (-0.2, 95% CI -0.3 to -0.1 s), 400-m walk (-9.7, -14.8 to -4.6 s), stair climb (-0.4, -0.6 to -0.2 s) and chair rise (-1.0, -1.4 to -0.7 s), with no differences between groups by 12 months, except for the 6-m fast walk (P < 0.001). CONCLUSION: Exercise either at the onset or after 6 months of ADT preserves/enhances muscle strength and physical function. However, to avoid initial treatment-related adverse effects on strength and function, exercise therapy should be implemented with initiation of ADT.

68Ga-PSMA PET/CT better characterises localised prostate cancer after MRI and transperineal prostate biopsy: Is 68Ga-PSMA PET/CT guided biopsy the future?

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Improved detection and reduced biopsies: the effect of a multiparametric magnetic resonance imaging-based triage prostate cancer pathway in a public teaching hospital.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

A prospective study of psychological distress after prostate cancer surgery.

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.

Clinical significance of the LacdiNAc-glycosylated prostate-specific antigen assay for prostate cancer detection.

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 < 0.0001), tPSA (AUC 0.712, P < 0.0001), and F/T PSA (AUC 0.661, P < 0.0001). The decision curve analysis showed that using a risk threshold of 20% and adding LDN-PSA and LDN-PSAD to the base model (age, digital rectal examination status, tPSA, and F/T PSA) permitted avoidance of even more biopsies without missing CSPC (9.89% and 18.11%, respectively vs 2.23% [base model]). In the preop-PSA cohort, LDN-PSA values positively correlated with tumor volume and tPSA and were significantly higher in pT3, pathological Gleason score ≥ 7. Limitations include limited sample size, retrospective nature, and no family history information prior to biopsy. LacdiNAc-glycosylated PSA is significantly better than the conventional PSA test in identifying patients with CSPC. This study was approved by the ethics committee of each institution ("The Study about Carbohydrate Structure Change in Urological Disease"; approval no. 2014-195).

Improved specificity with 68Ga PSMA PET/CT to detect clinically significant lesions "invisible" on multiparametric MRI of the prostate: a single institution comparative analysis with radical prostatectomy histology.

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 68Ga-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 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. 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 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). CONCLUSIONS: 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.