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Background: Conservative management is an option for prostate cancer (PCa) patients either with the objective of delaying or even avoiding curative therapy, or to wait until palliative treatment is needed. PIONEER, funded by the European Commission Innovative Medicines Initiative, aims at improving PCa care across Europe through the application of big data analytics., Objective: To describe the clinical characteristics and long-term outcomes of PCa patients on conservative management by using an international large network of real-world data., Design, Setting, and Participants: From an initial cohort of >100 000 000 adult individuals included in eight databases evaluated during a virtual study-a-thon hosted by PIONEER, we identified newly diagnosed PCa cases (n = 527 311). Among those, we selected patients who did not receive curative or palliative treatment within 6 mo from diagnosis (n = 123 146)., Outcome Measurements and Statistical Analysis: Patient and disease characteristics were reported. The number of patients who experienced the main study outcomes was quantified for each stratum and the overall cohort. Kaplan-Meier analyses were used to estimate the distribution of time to event data., Results and Limitations: The most common comorbidities were hypertension (35-73%), obesity (9.2-54%), and type 2 diabetes (11-28%). The rate of PCa-related symptomatic progression ranged between 2.6% and 6.2%. Hospitalization (12-25%) and emergency department visits (10-14%) were common events during the 1st year of follow-up. The probability of being free from both palliative and curative treatments decreased during follow-up. Limitations include a lack of information on patients and disease characteristics and on treatment intent., Conclusions: Our results allow us to better understand the current landscape of patients with PCa managed with conservative treatment. PIONEER offers a unique opportunity to characterize the baseline features and outcomes of PCa patients managed conservatively using real-world data., Patient Summary: Up to 25% of men with prostate cancer (PCa) managed conservatively experienced hospitalization and emergency department visits within the 1st year after diagnosis; 6% experienced PCa-related symptoms. The probability of receiving therapies for PCa decreased according to time elapsed after the diagnosis., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Patients undergoing prostate radiotherapy with an enlarged prostate can have short-term and long-term urinary complications. Currently, transurethral resection of the prostate (TURP) is the mainstay surgical intervention for men with urinary symptoms due to an enlarged prostate prior to radiotherapy. UroLift (NeoTract, Pleasanton, CA, USA) is a recent minimally invasive alternative, widely used in benign disease but is untested in men with prostate cancer., Methods and Analysis: A multicentre, two-arm study designed in collaboration with a Patient Reference Group to assess the feasibility of randomising men with prostate cancer and coexisting urinary symptoms due to prostate enlargement to TURP or UroLift ahead of radiotherapy. 45 patients will be enrolled and randomised (1:1) using a computer-generated programme to TURP or UroLift. Recruitment and retention will be assessed over a 12 month period. Information on clinical outcomes, adverse events and costs will be collected. Clinical outcomes and patient reported outcome measures will be measured at baseline, 6 weeks postintervention and 3 months following radiotherapy. A further 12 in-depth interviews will be conducted with a subset of patients to assess acceptability using the Theoretical Framework of Acceptability. Descriptive analysis on all outcomes will be performed using Stata (StataCorp V.2021)., Ethics and Dissemination: The trial has been approved by the Research Ethics Committee (REC) NHS Health Research Authority (HRA) and Health and Care Research Wales (HCRW). The results will be published in peer-reviewed journals, presented at national meetings and disseminated to patients via social media, charity and hospital websites., Trial Registration Number: NCT05840549., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Currently, follow-up protocols are applied equally to men on active surveillance (AS) for prostate cancer (PCa) regardless of findings at their initial follow-up biopsy. To determine whether less intensive follow-up is suitable following negative biopsy findings, we assessed the risk of converting to active treatment, any subsequent upgrading, volume progression (>33% positive cores), and serious upgrading (grade group >2) for negative compared with positive findings on initial follow-up biopsy., Methods: 13,161 men from 24 centres participating in the Global Action Plan Active Surveillance Prostate Cancer [GAP3] consortium database, with baseline grade group ≤2, PSA ≤ 20 ng/mL, cT-stage 1-2, diagnosed after 1995, and ≥1 follow-up biopsy, were included in this study. Risk of converting to treatment was assessed using multivariable mixed-effects survival regression. Odds of volume progression, any upgrading and serious upgrading were assessed using mix-effects binary logistic regression for men with ≥2 surveillance biopsies., Results: 27% of the cohort (n = 3590) had no evidence of PCa at their initial biopsy. Over 50% of subsequent biopsies in this group were also negative. A negative initial biopsy was associated with lower risk of conversion (adjusted hazard ratio: 0.45; 95% confidence interval [CI]: 0.42-0.49), subsequent upgrading (adjusted odds ratio [OR]: 0.52; 95%CI: 0.45-0.62) and serious upgrading (OR: 0.74; 95%CI: 0.59-92). Radiological progression was not assessed due to limited imaging data., Conclusion: Despite heterogeneity in follow-up schedules, findings from this global study indicated reduced risk of converting to treatment, volume progression, any upgrading and serious upgrading among men whose initial biopsy findings were negative compared with positive. Given the low risk of progression and high likelihood of further negative biopsy findings, consideration should be given to decreasing follow-up intensity for this group to reduce unnecessary invasive biopsies., (© 2022. The Author(s).)

Background: The mental wellbeing implications of a prostate cancer diagnosis are increasingly being realised. Significant mental health symptoms such as depression and anxiety, along with related constructs such as fear of cancer recurrence, body image and masculine self-esteem issues are prevalent. However, less is understood about potential prognostic factors for these outcomes in prostate cancer patients. Therefore, this study aims to primarily explore potential treatment, patient and oncological factors associated with mental wellbeing outcomes in the initial prostate cancer follow-up period., Methods: MIND-P is a multi-institutional prospective cohort study recruiting newly diagnosed prostate cancer patients for 12-month follow up. It will aim to recruit a final sample of 300 participants undergoing one of four treatment options: active surveillance, radical prostatectomy, radical radiotherapy, or hormone monotherapy. Questionnaire-based data collection consists of multiple validated mental, physical, and social wellbeing outcomes at baseline and 3-monthly intervals until study completion. Primary analysis will include evaluation of treatment undergone against multiple mental wellbeing outcomes. Secondary analysis will additionally explore multiple patient and oncological prognostic factors of potential importance, along with the cumulative incidence of these outcomes, symptom trajectory and their association with subsequent functional and social outcomes., Conclusion: This cohort study aims to add to the existing limited literature evaluating significant prognostic factors for multiple mental wellbeing outcomes in newly diagnosed prostate cancer patients. This may be of potential use for guiding future prognosis research and of clinical use for identifying individuals potentially requiring additional surveillance or support during routine cancer follow up., Study Registration: This study was prospectively registered on ClinicalTrials.gov (NCT04647474)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Brunckhorst et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: All patients living with cancer, including those with metastatic cancer, are encouraged to be physically active. This paper examines the secondary endpoints of an aerobic exercise intervention for men with metastatic prostate cancer., Methods: ExPeCT (Exercise, Prostate Cancer and Circulating Tumour Cells), was a multi-centre randomised control trial with a 6-month aerobic exercise intervention arm or a standard care control arm. Exercise adherence data was collected via heart rate monitors. Quality of life (FACT-P) and physical activity (self-administered questionnaire) assessments were completed at baseline, at 3 months and at 6 months., Results: A total of 61 patients were included (69.4 ± 7.3 yr, body mass index 29.2 ± 5.8 kg/m 2 ). The median time since diagnosis was 34 months (IQR 7-54). A total of 35 (55%) of participants had > 1 region affected by metastatic disease. No adverse events were reported by participants. There was no effect of exercise on quality of life (Cohen's d =  - 0.082). Overall adherence to the supervised sessions was 83% (329 out of 396 possible sessions attended by participants). Overall adherence to the non-supervised home exercise sessions was 72% (months 1-3) and 67% (months 3-6). Modelling results for overall physical activity scores showed no significant main effect for the group (p-value = 0.25) or for time (p-value = 0.24)., Conclusion: In a group of patients with a high burden of metastatic prostate cancer, a 6-month aerobic exercise intervention did not lead to change in quality of life. Further exercise studies examining the role of exercise for people living with metastatic prostate cancer are needed., Trial Registration: The trial was registered at clinicaltrials.gov (NCT02453139) on May 25th 2015., (© 2023. The Author(s).)

Background: Active surveillance (AS) is recommended for low-risk and some intermediate-risk prostate cancer. Uptake and practice of AS vary significantly across different settings, as does the experience of surveillance-from which tests are offered, and to the levels of psychological support., Objective: To explore the current best practice and determine the most important research priorities in AS for prostate cancer., Design, Setting, and Participants: A formal consensus process was followed, with an international expert panel of purposively sampled participants across a range of health care professionals and researchers, and those with lived experience of prostate cancer. Statements regarding the practice of AS and potential research priorities spanning the patient journey from surveillance to initiating treatment were developed., Outcome Measurements and Statistical Analysis: Panel members scored each statement on a Likert scale. The group median score and measure of consensus were presented to participants prior to discussion and rescoring at panel meetings. Current best practice and future research priorities were identified, agreed upon, and finally ranked by panel members., Results and Limitations: There was consensus agreement that best practice includes the use of high-quality magnetic resonance imaging (MRI), which allows digital rectal examination (DRE) to be omitted, that repeat standard biopsy can be omitted when MRI and prostate-specific antigen (PSA) kinetics are stable, and that changes in PSA or DRE should prompt MRI ± biopsy rather than immediate active treatment. The highest ranked research priority was a dynamic, risk-adjusted AS approach, reducing testing for those at the least risk of progression. Improving the tests used in surveillance, ensuring equity of access and experience across different patients and settings, and improving information and communication between and within clinicians and patients were also high priorities. Limitations include the use of a limited number of panel members for practical reasons., Conclusions: The current best practice in AS includes the use of high-quality MRI to avoid DRE and as the first assessment for changes in PSA, with omission of repeat standard biopsy when PSA and MRI are stable. Development of a robust, dynamic, risk-adapted approach to surveillance is the highest research priority in AS for prostate cancer., Patient Summary: A diverse group of experts in active surveillance, including a broad range of health care professionals and researchers and those with lived experience of prostate cancer, agreed that best practice includes the use of high-quality magnetic resonance imaging, which can allow digital rectal examination and some biopsies to be omitted. The highest research priority in active surveillance research was identified as the development of a dynamic, risk-adjusted approach., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Gonadotropin-releasing hormone agonists (GnRH) used in prostate cancer (PCa) are associated with atherogenic dyslipidaemia. It can be assumed that GnRH need to be used with greater caution in men with type 2 diabetes mellitus (T2DM). This study investigated association of GnRH with atherogenic lipids (AL) in PCa men with T2DM., Methods: Two cohorts including 38,311 men with 11 years follow-up based on Swedish national registers were defined (PCa-Exposure cohort and GnRH-Exposure cohort). Based on European guidelines on cardiovascular diseases (CVD), primary outcomes were defined as: 1.0 mmol/L increase in AL and lipid-lowering therapy (LLT) intensification. We used Cox proportional-hazards models and Kaplan-Meier curves to assess the association., Results: There was an association between GnRH and increased AL (i.e., triglyceride, PCa-Exposure cohort: HR 1.77, 95% CI 1.48-2.10; GnRH-Exposure cohort: HR 1.88, 95% CI 1.38-2.57). There was also an association between PCa diagnosis and increased AL. In contrast, no association between LLT intensification and GnRH was found., Conclusion: In this large population-based study, men with T2DM on GnRH for PCa had an increased risk of increased atherogenic lipids. These results highlight the need to closely monitor lipids and to be ready to intensify lipid-lowering therapy in men with T2DM on GnRH for PCa., (© 2022. The Author(s).)

Introduction: Quality of life in prostate cancer survivorship is becoming increasingly important, with mental and social wellbeing recognised as key components. However, limited global evaluation of psychosocial challenges experienced after treatment exists. Therefore, we aimed to explore the lived experiences of men who underwent radical treatment, and its psychosocial impact., Material and Methods: This qualitative study was conducted using 19 men who had undergone radical treatment (prostatectomy or radiotherapy) for their cancer. Semi-structured interviews were conducted exploring lived experiences of men after treatment. A Structured thematic analysis of collected data was undertaken, with an inductive co-construction of themes through the lens of the biopsychosocial model. Themes generated were considered within a psychological, social, and physical wellbeing framework., Results: An initial knowledge gap meant mental wellbeing was strongly impacted initially leading to a 'Diagnostic Blow and the Search for Clarity'. Doubt over individuals' future resulted in 'An Uncertain Future' in many men. Once treatment was completed a 'Reflective journey' began, with men considering their outcomes and decisions made. Social wellbeing was also impacted with many identifying the 'Emotional Repercussions' on their relationships and the impact their diagnosis had on their partner and family. Many subsequently sought to increase their support through 'The Social Network and Advocacy', while physical changes led to an increased need for 'Social Planning'. Finally, physical wellbeing was highlighted by a continual acknowledgement of the 'Natural process of ageing' leading to a reluctancy to seek help, whilst simultaneously attempting to improve existing health via 'The Health Kick'., Conclusions: Radical treatments have a considerable impact on mental and social wellbeing of individuals. Anxiety after diagnosis and significant uncertainty over individual futures exist, with physical complications of treatment leading to social repercussions. Future research should aim to identify forms of support to improve quality of life of these men., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Vyas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Importance: Men with type 2 diabetes have an increased risk of cardiovascular disease (CVD). Meanwhile, gonadotropin-releasing hormone (GnRH) agonists used in prostate cancer (PCa) are associated with increased risk of CVD., Objective: To evaluate the association between GnRH agonist use, PCa diagnosis per se, and CVD risk in men with type 2 diabetes., Design, Setting, and Participants: This nationwide population-based cohort study identified men with type 2 diabetes by use of data in the Prostate Cancer Data Base Sweden version 4.1 and the Swedish National Diabetes Register, with longitudinal data from 2006 to 2016. These data were used to create 2 cohorts, 1 including men with and without PCa and the other including men with PCa who received and did not receive GnRH agonists. Data analysis was conducted from January 2006 to December 2016., Exposures: Treatment with GnRH agonists and PCa diagnosis were the primary exposures., Main Outcomes and Measures: Primary outcome was a 10% increase in predicted 5-year CVD risk score. Secondary outcome was worsening hypertension as defined by the European Society of Hypertension Guidelines. Cox proportional hazards regression models were used to analyze the association., Results: The PCa exposure cohort included 5714 men (median [IQR] age, 72.0 [11.0]), and the non-PCa cohort included 28 445 men without PCa (median [IQR] age, 72.0 [11.0]). The GnRH agonist-exposure cohort included 692 men with PCa who received a GnRH agonist, compared with 3460 men with PCa who did not receive a GnRH agonist. Men with PCa receiving GnRH agonists had an increased estimated 5-year CVD risk score compared with men without PCa (hazard ratio [HR], 1.25; 95% CI, 1.16-1.36) and compared with men with PCa not receiving GnRH agonists (HR, 1.53; 95% CI, 1.35-1.74). Men receiving GnRH agonists had decreased blood pressure compared with men without PCa (HR, 0.70; 95% CI, 0.61-0.80) and compared with men with PCa not receiving GnRH agonists (HR, 0.68; 95% CI, 0.56-0.82)., Conclusions and Relevance: In this population-based cohort study, there was an increased risk of CVD in men with type 2 diabetes who received a GnRH agonist for PCa. These findings highlight the need to closely control CVD risk factors in men with type 2 diabetes treated with GnRH agonists. The association between GnRH agonist use and decreased blood pressure levels warrants further study.

Objectives: Side effects from the prolonged use of gonadotropin-releasing hormone (GnRH) agonists may lead to nonadherence to the treatment in men with advanced prostate cancer (PCa). We investigated the reasons contributing to nonadherence to GnRH agonists through interviews with men with PCa and focus groups with their health care professionals., Data Sources: The three stages of the study were validation of themes, interviews with men on GnRH agonists, and focus groups with oncology specialists and clinical nurse specialists. An experienced oncologist validated factors contributing to nonadherence identified from the literature. A total of 10 men with PCa were recruited from a large teaching hospital and were interviewed on a one-to-one basis using a topic guide. In stage three, two separate focus groups were held with oncology specialists and clinical nurse specialists treating men with PCa. The interviews and focus groups were audio recorded and transcribed verbatim. Initial codes identified from stage three were grouped into themes and thematically analyzed., Conclusion: Themes identified from the interviews and focus groups influencing adherence to treatment were side effects of treatment, patient belief system, benefits outweigh harm, quality of life over quantity of life, social support, and patient-clinician relationship. Although side effects such as hot flushes and loss of libido were sometimes overwhelming for many, these men felt that treatment benefits outweighed harm., Implications for Nursing Practice: Reasons leading to nonadherence can be multifactorial and unique to each patient. Employing different strategies by health care professionals may lead to the eventual acceptance of treatment, while also acknowledging their reasons for nonadherence., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest with regard to the content of this article., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: There is a growing emphasis on improving quality of life of people with prostate cancer. However, those undergoing active surveillance remain underrepresented in the literature with less known about their unique challenges. Therefore, we aimed to explore their lived experiences post diagnosis and its effect on their mental, social, and physical wellbeing., Methods: Qualitative semi-structured interviews were conducted with 13 men undergoing active surveillance for low-risk disease. Thematic analysis was used to inductively co-construct themes through the lens of the biopsychosocial model., Results: Mental wellbeing was strongly affected in our participants due to the overwhelming emotional impact of their diagnosis resulting in an 'Emotional Diagnostic Disequilibrium'. Informational awareness and education about prostate cancer helped patients with 'Recognition of the Impact'. Patients experienced an 'Unsettling Monitoring Cycle' due to the increased fear and anxiety around PSA monitoring appointments, with some men ignoring their mental wellbeing needs as their disease is 'A Future Problem'. 'Concealment of Diagnosis' left many feeling isolated and highlighted an important coping mechanisms in the 'Importance of a Social Support Network' theme. Finally, physical health mostly changed through alterations in health behaviour, leading to 'A Healthier Lifestyle' with increasing attribution of physical symptoms to age through 'Symptomatic Overshadowing'., Conclusion: The greatest disease impact on men's wellbeing was at the time of diagnosis, with a subsequent cyclical anxiety and fear of disease progression prominent around monitoring appointments. Future research should explore ways to better support patients with these issues and at these times, improving their quality of life., (© 2022. The Author(s).)

Background: Invadopodia, actin-rich structures that release metallo-proteases at the interface with extra-cellular matrix, in a punctate manner are thought to be important drivers of tumour invasion. Invadopodia formation has been observed in-vitro and in-vivo in numerous metastatic cell lines derived from multiple tumour types. However, prostate cancer cell lines have not been routinely reported to generate invadopodia and the few instances have always required external stimulation., Methods: In this study, the invasive potential of primary prostate adenocarcinoma cell lines, which have never been fully characterised before, was investigated both in-vitro invadopodia assays and in-vivo zebrafish dissemination assay. Subsequently, circulating tumour cells from prostate cancer patients were isolated and tested in the invadopodia assay., Results: Retention of E-cadherin and N-cadherin expression indicated a transitional state of EMT progression, consistent with the idea of partial EMT that has been frequently observed in aggressive prostate cancer. All cell lines tested were capable of spontaneous invadopodia formation and possess a significant degradative ability in-vitro under basal conditions. These cell lines were invasive in-vivo and produced visible metastasis in the zebrafish dissemination assay. Importantly we have proceeded to demonstrate that circulating tumour cells isolated from prostate cancer patients exhibit invadopodia-like structures and degrade matrix with visible puncta. This work supports a role for invadopodia activity as one of the mechanisms of dissemination employed by prostate cancer cells., Conclusion: The combination of studies presented here provide clear evidence that invadopodia activity can play a role in prostate cancer progression., (© 2022. The Author(s).)

Objectives: As part of the PIONEER Consortium objectives, we have explored which diagnostic and prognostic factors (DPFs) are available in relation to our previously defined clinician and patient-reported outcomes for prostate cancer (PCa)., Design: We performed a systematic review to identify validated and non-validated studies., Data Sources: MEDLINE, Embase and the Cochrane Library were searched on 21 January 2020., Eligibility Criteria: Only quantitative studies were included. Single studies with fewer than 50 participants, published before 2014 and looking at outcomes which are not prioritised in the PIONEER core outcome set were excluded., Data Extraction and Synthesis: After initial screening, we extracted data following the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of prognostic factor studies (CHARMS-PF) criteria and discussed the identified factors with a multidisciplinary expert group. The quality of the included papers was scored for applicability and risk of bias using validated tools such as PROBAST, Quality in Prognostic Studies and Quality Assessment of Diagnostic Accuracy Studies 2., Results: The search identified 6604 studies, from which 489 DPFs were included. Sixty-four of those were internally or externally validated. However, only three studies on diagnostic and seven studies on prognostic factors had a low risk of bias and a low risk concerning applicability., Conclusion: Most of the DPFs identified require additional evaluation and validation in properly designed studies before they can be recommended for use in clinical practice. The PIONEER online search tool for DPFs for PCa will enable researchers to understand the quality of the current research and help them design future studies., Ethics and Dissemination: There are no ethical implications., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Context: Prostate cancer (PCa) is the second most common cancer among men worldwide. Urinary, bowel, and sexual function, as well as hormonal symptoms and health-related quality of life (HRQoL), were prioritised by patients and professionals as part of a core outcome set for localised PCa regardless of treatment type., Objective: To systematically review the measurement properties of patient-reported outcome measures (PROMs) used in localised PCa and recommend PROMs for use in routine practice and research settings., Evidence Acquisition: The psychometric properties of PROMs measuring functional and HRQoL domains used in randomised controlled trials including patients with localised PCa were assessed according to the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) methodology. MEDLINE and Embase were searched to identify publications evaluating psychometric properties of the PROMs. The characteristics and methodological quality of the studies included were extracted, tabulated, and assessed according to the COSMIN criteria., Evidence Synthesis: Overall, 27 studies evaluating psychometric properties of the Expanded Prostate Cancer Index Composite (EPIC), University of California-Los Angeles Prostate Cancer Index (UCLA-PCI), European Organisation for Research and Treatment of Cancer (EORTC) quality of life core 30 (QLQ-C30) and prostate cancer 25 (QLQ-PR25) modules, International Index of Erectile Function (IIEF), and the 36-item (SF-36) and 12-item Short-Form health survey (SF-12) PROMs were identified and included in the systematic review. EPIC and EORTC QLQ-C30, a general module that assesses patients' physical, psychological, and social functions, were characterised by high internal consistency (Cronbach's α 0.46-0.96 and 0.68-0.94 respectively) but low content validity. EORTC QLQ-PR25, which is primarily designed to assess PCa-specific HRQoL, had moderate content validity and internal consistency (Cronbach's α 0.39-0.87). UCLA-PCI was characterised by moderate content validity and high internal consistency (Cronbach's α 0.21-0.94). However, it does not directly assess hormonal symptoms, whereas EORTC QLQ-PR25 does., Conclusion: The tools with the best evidence for psychometric properties and feasibility for use in routine practice and research settings to assess PROMs in patients with localised PCa were EORTC QLQ-C30 and QLQ-PR25. Since EORTC QLQ-C30 is a general module that does not directly assess PCa-specific issues, it should be adopted in conjunction with the QLQ-PR25 module., Patient Summary: We reviewed and appraised the measurement properties of patient-reported outcome measure questionnaires used for patients with localised prostate cancer. We found good evidence to suggest that two questionnaires (EORTC QLQ-C30 and QLQ-PR25) can be used to measure urinary, bowel, and sexual functions and health-related quality of life., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Pathways involving sex hormones and insulin-like growth factors (IGFs) have been proposed to explain, in part, the lower risk of prostate cancer among men with diabetes. To gain insights into potential biological mechanisms we explored differences in serum concentrations of sex hormones and IGFs across the trajectory from normoglycemia to prediabetes to poorly controlled diabetes., Methods: Using cross-sectional data from the National Health and Nutrition Examination Survey III we examined differences in levels of circulating sex hormones, sex hormone-binding globulin (SHBG), IGF-1, and IFG-binding protein 3 (IGFBP-3), according to diabetes status: no diabetes [n = 648], prediabetes [n = 578], undiagnosed diabetes [n = 106], well-controlled diabetes [n = 42], and poorly controlled diabetes [n = 56]. Adjusted geometric mean concentrations were derived using multivariable linear regression, adjusted for age, race, and other lifestyle factors., Results: Total testosterone concentrations were lower among prediabetics (4.89 ng/mL, 95% confidence interval (CI) 4.95-5.21) than men without prediabetes/diabetes (5.29 ng/mL, 95% CI 5.06-5.53) but did not reduce further across diabetes groups. Concentrations of estradiol, estimated free testosterone, SHGB, IGF-1, and IGFBP-3 did not differ. While the ratio of IGF-1 to IGFBP-3 was lower among men with prediabetics and undiagnosed diabetes than men without prediabetes/diabetes, there was no trend across groups. A positive trend for the ratio of estradiol-to-testosterone levels was observed across groups (p trend = 0.045)., Conclusion: Our findings do not provide clear support for either an androgen driven or IGF-driven pathway for the inverse association between diabetes and prostate cancer risk., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: The ReIMAGINE Consortium was conceived to develop risk-stratification models that might incorporate the full range of novel prostate cancer (PCa) diagnostics (both commercial and academic)., Methods: ReIMAGINE Risk is an ethics approved (19/LO/1128) multicentre, prospective, observational cohort study which will recruit 1000 treatment-naive men undergoing a multi-parametric MRI (mpMRI) due to an elevated PSA (≤20ng/ml) or abnormal prostate examination who subsequently had a suspicious mpMRI (score≥3, stage ≤T3bN0M0). Primary outcomes include the detection of ≥Gleason 7 PCa at baseline and time to clinical progression, metastasis and death. Baseline blood, urine, and biopsy cores for fresh prostate tissue samples (2 targeted and 1 non-targeted) will be biobanked for future analysis. High-resolution scanning of pathology whole-slide imaging and MRI-DICOM images will be collected. Consortium partners will be granted access to data and biobanks to develop and validate biomarkers using correlation to mpMRI, biopsy-based disease status and long-term clinical outcomes., Results: Recruitment began in September 2019(n = 533). A first site opened in September 2019 (n = 296), a second in November 2019 (n = 210) and a third in December 2020 (n = 27). Acceptance to the study has been 65% and a mean of 36.5ml(SD+/-10.0), 12.9ml(SD+/-3.7) and 2.8ml(SD+/-0.7) urine, plasma and serum donated for research, respectively. There are currently 4 academic and 15 commercial partners spanning imaging (~9 radiomics, artificial intelligence/machine learning), fluidic (~3 blood-based and ~2urine-based) and tissue-based (~1) biomarkers., Conclusion: The consortium will develop, or adjust, risk models for PCa, and provide a platform for evaluating the role of novel diagnostics in the era of pre-biopsy MRI and targeted biopsy., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Hashim U Ahmed receives grant funding from Sonacare Inc., Sophiris Biocorp and Boston commercial entities. Hashim U Ahmed is awarded academic funds from the MRC, CRUK, The Wellcome Trust, The British Medical Association (BMA), The Urology Foundaiton (TUF), Prostate Cancer U.K. (PCUK) and Imperial Health. Mark Emberton serves as a consultant/educator/trainer to Sonacare Inc., Exact Imaging, Angiodynamics Inc and Profound Medical. Acknowledgements - Mark Emberton receives research support from the United Kingdom’s National Institute of Health Research (NIHR) UCLH/UCL Biomedical Research Centre. Caroline M Moore receives funding from the Prostate Cancer UK, Movember, the Medical Research Council, Cancer Research UK and the NIHR. She receives fees for HIFU proctoring from SonaCare. She has received speaker fees from Astellas, and Jannsen. She carries out research into photodyanamic therapy supported by Spectracure. Shonit Punwani receives research support from the United Kingdom’s National Institute of Health Research (NIHR) UCLH/UCL Biomedical Research Centre Ton Coolen receives funding from Cancer Research UK and is Director of Saddle Point Science Ltd. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Introduction: For clinical decision-making, an estimate of remaining lifetime is needed to assess benefit against harm of a treatment during the remaining lifespan. Here, we describe how to predict life expectancy based on age, Charlson Comorbidity Index (CCI) and a Drug Comorbidity Index (DCI), whilst also considering potential future changes in CCI and DCI using population-based data on Swedish men., Methods: Simulations based on annual updates of vital status, CCI and DCI were used to estimate life expectancy at population level. The probabilities of these transitions were determined from generalised linear models using prostate cancer-free comparison men in PCBaSe Sweden. A simulation was performed for each combination of age, CCI, and DCI. Survival curves were created and compared to observed survival. Life expectancy was then calculated as the area under the simulated survival curve., Results: There was good agreement between observed and simulated survival curves for most ages and comorbidities, except for younger men. With increasing age and comorbidity, there was a decrease in life expectancy. Cross-validation based on six regions in Sweden also showed that simulated and observed survival was similar., Conclusion: Our proposed method provides an alternative statistical approach to estimate life expectancy at population level based on age and comorbidity assessed by routinely collected information on diagnoses and filled prescriptions available in nationwide health care registers., (© 2022. The Author(s).)

Background: Gonadotropin Releasing Hormones agonists (GnRH), which are first line treatment for metastatic prostate cancer (PCa), increase risk of type 2 diabetes mellitus (T2DM). This study aims to quantify the association of use of GnRH with diabetes control in PCa men with T2DM., Methods: Nationwide population-based cohort study in the Swedish National Diabetes Register and Prostate Cancer data Base Sweden 4.1, on the association between GnRH and diabetes control in T2DM men with PCa by comparing T2DM men with PCa vs. without PCa, as well as comparing T2DM men with PCa on or not on GnRH. The primary exposure was use of GnRH. Worsening diabetes control was the primary outcome, defined as: 1) HbA1c rose to 58 mmol/mol or higher; 2) HbA1c increase by 10 mmol/mol or more; 3) Start of antidiabetic drugs or switch to insulin. We also combined all above definitions. Cox proportional hazards regression was used to analyze the association., Results: There were 5714 T2DM men with PCa of whom 692 were on GnRH and 28,445 PCa-free men with T2DM with similar baseline characteristics. Diabetes control was worse in men with GnRH vs. PCa-free men (HR: 1.24, 95% CI: 1.13-1.34) as well as compared with PCa men without GnRH (HR:1.58, 95% CI: 1.39-1.80), when we defined the worsening control of diabetes by combining all definitions above., Conclusion: Use of GnRH in T2DM men with PCa was associated with worse glycemic control. The findings highlight the need to closely monitor diabetes control in men with T2DM and PCa starting GnRH., (© 2021. The Author(s).)

Introduction: The primary objective of the ReIMAGINE Prostate Cancer Screening Study is to explore the uptake of an invitation to prostate cancer screening using MRI., Methods and Analysis: The ReIMAGINE Prostate Cancer Screening Study is a prospective single-centre feasibility study. Eligible men aged 50-75 years with no prior prostate cancer diagnosis or treatment will be identified through general practitioner practices and randomly selected for invitation. Those invited will be offered an MRI scan and a prostate-specific antigen (PSA) blood test. The screening MRI scan consists of T2-weighted, diffusion-weighted and research-specific sequences, without the use of intravenous contrast agents. Men who screen positive on either MRI or PSA density will be recommended to have standard of care (National Health Service) tests for prostate cancer assessment, which includes multiparametric MRI. The study will assess the acceptability of an MRI-based prostate screening assessment and the prevalence of cancer detected in MRI-screened men. Summary statistics will be used to explore baseline characteristics in relation to acceptance rates and prevalence of cancer., Ethics and Dissemination: ReIMAGINE Prostate Cancer Screening is a single-site screening study to assess the feasibility of MRI as a screening tool for prostate cancer. Ethical approval was granted by London-Stanmore Research Ethics Committee Heath Research Authority (reference 19/LO/1129). Study results will be published in peer-reviewed journals after completion of data analysis and used to inform the design of a multicentre screening study in the UK., Trial Registration Number: ClinicalTrials.gov Registry (NCT04063566)., Competing Interests: Competing interests: CMM receives funding from the Prostate Cancer UK, Movember, the Medical Research Council, Cancer Research UK and the NIHR. She receives fees for HIFU proctoring from SonaCare. She has received speaker fees from Astellas and Jannsen. She carries out research into photodynamic therapy supported by Spectracure. ME serves as a consultant/educator/trainer to Sonacare, Exact Imaging, Angiodynamics and Profound Medical., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Objective: To determine the risk of disease progression and conversion to active treatment following a negative biopsy while on active surveillance (AS) for prostate cancer (PCa)., Patients and Methods: Men on an AS programme at a single tertiary hospital (London, UK) between 2003 and 2018 with confirmed low-intermediate-risk PCa, Gleason Grade Group <3, clinical stage 30% positive cores, magnetic resonance imaging (MRI) Likert score >3/T3 or PSA level of >20 ng/mL. Conversion to treatment included radical or hormonal treatment., Results: Among the 460 eligible patients, 23% had negative follow-up biopsy findings. The median follow-up was 62 months, with one to two repeat biopsies and two MRIs per patient during that period. Negative biopsy findings at first repeat biopsy were associated with decreased risk of converting to active treatment (hazard ration [HR] 0.18, 95% confidence interval [CI] 0.09-0.37; P < 0.001), suspicion of disease progression (HR 0.56, 95% CI: 0.34-0.94; P = 0.029), and upgrading (HR 0.48, 95% CI 0.23-0.99; P = 0.047). Data are limited by fewer men with multiple follow-up biopsies., Conclusion: A negative biopsy finding at the first scheduled follow-up biopsy among men on AS for PCa was strongly associated with decreased risk of subsequent upgrading, clinical or radiological suspicion of disease progression, and conversion to active treatment. A less intense surveillance protocol should be considered for this cohort of patients., (© 2020 The Authors BJU International © 2020 BJU International.)

Purpose: We sought to identify and validate known predictors of disease reclassification at 1 or 4 years to support risk-based selection of patients suitable for active surveillance., Materials and Methods: An individual participant data meta-analysis using data from 25 established cohorts within the Movember Foundations GAP3 Consortium. In total 5,530 men were included. Disease reclassification was defined as any increase in Gleason grade group at biopsy at 1 and 4 years. Associations were estimated using random effect logistic regression models. The discriminative ability of combinations of predictors was assessed in an internal-external validation procedure using the AUC curve., Results: Among the 5,570 men evaluated at 1 year, we found 815 reclassifications to higher Gleason grade group at biopsy (pooled reclassification rate 13%, range 0% to 31%). Important predictors were age, prostate specific antigen, prostate volume, T-stage and number of biopsy cores with prostate cancer. Among the 1,515 men evaluated at 4 years, we found 205 reclassifications (pooled reclassification rates 14%, range 3% to 40%), with similar predictors. The average areas under the receiver operating characteristic curve at internal-external validation were 0.68 and 0.61 for 1-year and 4-year reclassification, respectively., Conclusions: Disease reclassification occurs typically in 13% to 14% of biopsies at 1 and 4 years after the start of active surveillance with substantial between-study heterogeneity. Current guidelines might be extended by considering prostate volume to improve individualized selection for active surveillance. Additional predictors are needed to improve patient selection for active surveillance.

Fatty acid synthase (FASN) is commonly overexpressed in prostate cancer and associated with tumour progression. FASN is responsible for de novo synthesis of the fatty acid palmitate; the building block for protein palmitoylation. A functional role for FASN in regulating cell proliferation is widely accepted. We recently reported that FASN activity can also mediate prostate cancer HGF-mediated cell motility. Moreover, we found that modulation of FASN expression specifically impacts on the palmitoylation of RhoU. Findings we will describe here. We now report that loss of FASN expression also impairs HGF-mediated cell dissociation responses. Taken together our results provide compelling evidence that FASN activity directly promotes cell migration and supports FASN as a potential therapeutic target in metastatic prostate cancer.

Background: Experiences of African/Afro-Caribbean men on active surveillance (AS) for prostate cancer (PCa) in the United Kingdom (UK) are not well documented. We compared follow-up appointments, adherence, and clinical outcomes among African/Afro-Caribbean men on AS at a high-volume UK hospital with other ethnicities., Methods: Men with confirmed low-intermediate risk Pca who attended the AS clinic (2005-2016) and had undergone ≥1 follow-up biopsy (n = 458) were included. Non-adherence (defined as >20% missed appointments), suspicion of disease progression (any upgrading, >30% positive cores, cT-stage > 3, PIRADS > 3), any upgrading from diagnostic biopsy and conversion to active treatment (prostatectomy, radiotherapy or hormone therapy) according to ethnicity (African/Afro-Caribbean versus other ethnicities) were assessed using multivariable regression analysis., Results: Twenty-three percent of eligible men were recorded as African/Afro-Caribbean, while the remainder were predominantly Caucasian. African/Afro-Caribbean men had slightly lower PSA at diagnosis (median 5.0 vs. 6.0 ng/mL) and more positive cores at diagnosis (median 2 vs. 1). They had a substantially higher rate of non-attendance at scheduled follow-up visits (24% vs. 10%, p < 0.001). Adjusted analyses suggest African/Afro-Caribbean men may be at increased risk of disease progression (hazard ratio [HR]: 1.38; 95% confidence interval [CI] 0.99-1.91, P = 0.054) and upgrading (HR: 1.29; 95% CI 0.87-1.92, P = 0.305), though neither reached statistical significance. No difference in risk of conversion to treatment was observed between ethnic groups (HR: 1.03; 95% CI 0.64-1.47, P = 0.873)., Conclusions: African/Afro-Caribbean men on AS for PCa in the UK are less likely to adhere to scheduled appointments, suggesting a more tailored service addressing their specific needs may be required. While African/Afro-Caribbean men were no more likely to convert to treatment than Caucasian/other men, findings of a potentially higher risk of disease progression signal the need for careful selection and monitoring of African/Afro-Caribbean men on AS. Larger prospective, multicentre studies with longer follow-up are required to provide more definitive conclusions.

Background: Psychiatric implications of prostate cancer are increasingly recognised, having important effects on oncological and functional outcomes. However, findings for co-occurring depression, anxiety, and suicidality remain variable. Therefore, this review of observational studies aimed to establish best estimates of the prevalence and rates of these outcomes in prostate cancer patients., Methods: A systematic literature search was conducted using MEDLINE, Scopus, PsycInfo, and Cochrane Library databases from inception up to 26 May 2020. Observational studies using validated methods for evaluating prevalences of depression, anxiety and suicidal ideation, or suicide mortality rates post prostate cancer diagnosis were included. Random effect models were used to calculate pooled prevalences of depressive and anxiety symptoms or disorders, and suicidal ideation post diagnosis. Additionally, pooled crude suicide mortality rates per 100,000 person years were calculated. Heterogeneity was explored using a stratified analysis., Results: Of 3537 articles screened, 117 were included. Pooled prevalence for depressive disorders was 5.81% (95% CI 4.36-7.46) in 11 studies, representing 655,149 patients. Significant depressive symptoms were identified in 17.07% (15.14-19.09) across 32,339 patients and 76 studies. In total, 16.86% (14.92-18.89) had significant anxiety symptoms in 56 studies combining 24,526 patients. In 6,173 patients and eight studies, recent suicidal ideation was present in 9.85% (7.31-12.70). Crude suicide mortality rate after diagnosis was 47.1 (39.85-54.96) per 100,000 person years in 12 studies. Significant heterogeneity was seen with potential sources identified through our sensitivity analysis including diagnostic method utilised, study size and location of study., Conclusions: The mental health impact in patients with prostate cancer is significant. Depressive, anxiety, and suicidal symptoms were common. Additionally, a high suicide mortality rate was identified when compared to general population estimates. Screening of patients and integration of physical and mental health care should be evaluated further to improve quality of life and functional outcomes.

Background: The routine clinical use of serum prostatic specific antigen (PSA) testing has allowed earlier detection of low-grade prostate cancer (PCa) with more favourable characteristics, leading to increased acceptance of management by active surveillance (AS). AS aims to avoid over treatment in men with low and intermediate-risk PCa and multiple governing bodies have described several AS protocols. This study provides a descriptive profile of the Guy's and St Thomas NHS Foundation Trust (GSTT) AS cohort as a platform for future research in AS pathways in PCa., Methods: Demographic and baseline characteristics were retrospectively collected in a database for patients at the GSTT AS clinic with prospective collection of follow-up data from 2012. Seven hundred eighty-eight men being monitored at GSTT with histologically confirmed intermediate-risk PCa, at least 1 follow-up appointment and diagnostic characteristics consistent with AS criteria were included in the profile. Descriptive statistics, Kaplan-Meier survival curves and multivariable Cox proportion hazards regression models were used to characterize the cohort., Discussion: A relatively large proportion of the cohort includes men of African/Afro-Caribbean descent (22%). More frequent use of magnetic resonance imaging and trans-perineal biopsies at diagnosis was observed among patients diagnosed after 2012. Those who underwent trans-rectal ultrasound diagnostic biopsy received their first surveillance biopsy 20 months earlier than those who underwent trans-perineal diagnostic biopsy. At 3 years, 76.1% men remained treatment free. Predictors of treatment progression included Gleason score 3 + 4 (Hazard ratio (HR): 2.41, 95% Confidence interval (CI): 1.79-3.26) and more than 2 positive cores taken at biopsy (HR: 2.65, CI: 1.94-3.62). A decreased risk of progressing to treatment was seen among men diagnosed after 2012 (HR: 0.72, CI: 0.53-0.98)., Conclusion: An organised biopsy surveillance approach, via two different AS pathways according to the patient's diagnostic method, can be seen within the GSTT cohort. Risk of patients progressing to treatment has decreased in the period since 2012 compared with the prior period with more than half of the cohort remaining treatment free at 5 years, highlighting that the fundamental aims of AS at GSTT are being met. Thus, this cohort is a good resource to investigate the AS treatment pathway.

ReIMAGINE Screening is a single-centre study assessing the feasibility of biparametric magnetic resonance imaging as a screening tool for prostate cancer. The study outcomes will take us a step towards more accurate and less harmful prostate cancer screening., (Copyright © 2021. Published by Elsevier B.V.)

Observational studies in prostate cancer (PCa) have shown an increased risk of cardiovascular disease (CVD) following gonadotropin-releasing hormone (GnRH) agonists, whereas randomised-controlled trials have shown no associations. Compared to GnRH agonists, GnRH antagonists have shown less atherosclerotic effects in preclinical models. We used real-world data from five countries to investigate CVD risk following GnRH agonists and antagonists in PCa men. Data sources included cancer registries, primary and secondary healthcare databases. CVD event was defined as an incident or fatal CVD. Multivariable Cox proportional hazard models estimated hazard ratios (HRs) and 95% confidence intervals (CIs), which were pooled using random-effects meta-analysis. Stratified analyses were conducted by history of CVD and age (75 years). A total of 48 757 men were on GnRH agonists and 2144 on GnRH antagonists. There was no difference in risk of any CVD for men on GnRH antagonists and agonists (HR: 1.25; 95% CI: 0.96-1.61; I 2 : 64%). Men on GnRH antagonists showed increased risk of acute myocardial infarction (HR: 1.62; 95% CI: 1.11-2.35; I 2 : 0%) and arrhythmia (HR: 1.55; 95% CI: 1.11-2.15, I 2 : 17%) compared to GnRH agonists. Having a history of CVD was found to be an effect modifier for the associations with some CVD subtypes. Overall, we did not observe a difference in risk of overall CVD when comparing GnRH antagonists with agonists-though for some subtypes of CVD we noted an increased risk with antagonists. Further studies are required to address potential confounding caused by unadjusted variables such as severity of CVD history and PCa stage., (© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.)

We investigated the association between metabolic syndrome (MetS) and its components and risk of prostate cancer (PCa) in a cohort of men enrolled in the UK Biobank. Our study cohort included 220 622 PCa-free men with baseline measurements of triglycerides (TGs), HDL-cholesterol (HDL), glycated hemoglobin (HbA1c), blood pressure (BP), and waist circumference (WC). Multivariable Cox proportional hazards regression was used to analyze associations with PCa for: individual metabolic components (TG, HDL, HbA1c, BP, WC), combinations of two and three components, and MetS overall (three or more components). We conducted mediation analyses to examine potential hormonal and inflammatory pathways (total testosterone [TT], C-reactive protein [CRP], insulin-like growth factor 1 [IGF-1]) through which MetS components may influence PCa risk. A total of 5409 men in the study developed PCa during a median follow-up of 6.9 years. We found no significant association between MetS and PCa risk (hazard ratio [HR] = 0.99, 95% confidence interval [CI] = 0.92-1.06). No associations were found with PCa risk and individual measurements of TG, HDL, BP, or WC. However, an inverse association was observed with elevated HbA1c (≥42 mmol/mol) (HR = 0.89, 95% CI = 0.79-0.98). Consistent inverse associations were observed between HbA1c and risk of PCa. Mediation analysis revealed TT, CRP, and IGF-1 as potential mediating factors for this association contributing 10.2%, 7.1%, and 7.9% to the total effect, respectively. Overall MetS had no association with PCa risk. However, a consistent inverse association with PCa risk was found for HbA1c. This association may be explained in part through hormonal and inflammatory pathways., (© 2020 Union for International Cancer Control.)

Introduction: As part of the PIONEER (Prostate Cancer Diagnosis and Treatment Enhancement Through the Power of Big Data in Europe) Consortium, we will explore which diagnostic and prognostic factors (DPFs) are currently being researched to previously defined clinical and patient-reported outcomes for prostate cancer (PCa)., Methods and Analysis: This research project will follow the following four steps: (1) a broad systematic literature review of DPFs for all stages of PCa, covering evidence from 2014 onwards; (2) discussion of systematic review findings by a multidisciplinary expert panel; (3) risk of bias assessment and applicability with Prediction model Risk Of Bias Assessment Tool criteria, Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and the Quality In Prognosis Studies tool (QUIPS) and (4) additional quantitative assessments if required., Ethics and Dissemination: We aim to develop an online tool to present the DPFs identified in this research and make them available across all stakeholders. There are no ethical implications., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Purpose: Existing research indicates that physical activity (PA) is beneficial to men with prostate cancer (PCa). We examined the potential of a single-contact peer-support-based behavioural intervention to promote PA engagement in men treated for PCa., Methods: A mixed methods design was employed, comprising a two-arm pragmatic trial and semi-structured interviews. The intervention was a 10-min PA-based presentation by a former patient, delivered in group seminars that are provided for patients as standard care. Seminars were alternately allocated to (a) cancer exercise specialist talk + patient speaker talk or (b) cancer exercise specialist talk only. Self-reported PA, exercise motivation, quality of life, fatigue and clinical and demographic characteristics were obtained from n = 148 (intervention: n = 69; control: n = 79) patients immediately prior to the seminar, and at follow-up ≈ 100 days later. Data were analysed using ANCOVA models and χ 2 tests. Fourteen semi-structured interviews with intervention participants, which explored how the intervention was experienced, were analysed using a grounded theory-style approach., Results: The intervention had no significant effect on quantitatively self-reported PA (p = 0.4). However, the intervention was statistically and clinically beneficial for fatigue (p = 0.04) and quality of life (p = 0.01). Qualitative analysis showed that the intervention was beneficial to psychological wellbeing and some participants had increased intention to engage in PA as a result of the intervention., Conclusions: A brief one-off PA-based presentation for men with PCa, delivered by a former patient alongside cancer exercise specialist advice, may result in clinically significant benefits to quality of life and may influence PA intention in certain individuals.

Background: Although prostate cancer is a leading cause of cancer death, its aetiology is not well understood. We aimed to identify novel biochemical factors for prostate cancer incidence and mortality in UK Biobank., Methods: A range of cardiovascular, bone, joint, diabetes, renal and liver-related biomarkers were measured in baseline blood samples collected from up to 211,754 men at recruitment and in a subsample 5 years later. Participants were followed-up via linkage to health administrative datasets to identify prostate cancer cases. Hazard ratios (HRs) and 95% confidence intervals were calculated using multivariable-adjusted Cox regression corrected for regression dilution bias. Multiple testing was accounted for by using a false discovery rate controlling procedure., Results: After an average follow-up of 6.9 years, 5763 prostate cancer cases and 331 prostate cancer deaths were ascertained. Prostate cancer incidence was positively associated with circulating vitamin D, urea and phosphate concentrations and inversely associated with glucose, total protein and aspartate aminotransferase. Phosphate and cystatin-C were the only biomarkers positively and inversely, respectively, associated with risk in analyses excluding the first 4 years of follow-up. There was little evidence of associations with prostate cancer death., Conclusion: We found novel associations of several biomarkers with prostate cancer incidence. Future research will examine associations by tumour characteristics.

Background: While open-label randomized controlled trials (RCT) are common in oncology, some concerns have been expressed with regard to Patient-Reported Outcomes (PRO)-based claims stemming from these studies. We aimed to investigate the impact of open-label design in the context of prostate cancer (PCa) RCTs with PRO data., Methods: Randomized controlled trials of PCa with a PRO endpoint published between 2004 and 2018 were considered. RCTs were systematically evaluated on the basis of previously defined criteria, including international PRO reporting quality standards and the Cochrane Collaboration's tool for assessing Risk of Bias. The rate of concordance was estimated and compared between traditional clinical outcomes (eg, survival or tumor response) and PRO in open and blinded RCTs., Results: We identified 110 RCTs published between 2004 and 2018, of which 62% (n = 68) were open-label. The general characteristics of PCa RCTs were not different according to their design (open-label vs blinded). The proportion of PCa RCTs with high-quality PRO reporting was not different between open-label RCTs and blinded RCTs (41.2% vs 38.1%; P = .75). No statistically significant difference was found between PRO results and concordance with traditional clinical outcomes according to the study design., Conclusion: Our findings suggest that there is no evidence of significant bias for PROs due to the absence of blinding in the context of PCa RCTs. Further analyses should be conducted in other cancer disease sites., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Spironolactone, a cheap effective diuretic used to manage hypertension and heart failure, also has anti-androgenic effects through its non-selective binding to steroid receptors, and hence may affect prostate cancer (PCa) risk. This study investigated the association between spironolactone use and PCa risk. For comparison, we also examined associations with thiazide diuretics which do not have anti-androgenic properties., Methods: A matched case-control study was undertaken using population-wide data from the Prostate Cancer Data Base Sweden (PCBaSe). All PCa cases diagnosed from 2014 to 2016 were matched by birth year and county with PCa-free controls selected from the general population (1:5). Multivariable conditional logistic regression was used to examine associations between spironolactone use (dose and duration) and PCa risk, and similarly for thiazides., Results: Three percent of the 31,591 cases and 4% of the 156,802 controls had been prescribed spironolactone. Multivariable analyses indicated reduced risk of PCa among those ever exposed to spironolactone (odds ratio [OR] 0.83; 95% confidence interval [CI]: 0.76-0.89), with a stronger association for current users (OR: 0.77, 95% CI: 0.69-0.86) than past users (OR: 0.88; 95% CI: 0.79-0.97) and decreasing risk with increasing dose (p-trend < 0.001). No association was observed for thiazide exposure and PCa risk. Biases due to differences in prescribing patterns or frequency of PSA testing may have influenced these findings., Conclusion: PCa risk was reduced among men exposed to the diuretic spironolactone. Further investigation of spironolactone's potential chemopreventive effects is warranted.

Background: Prostate cancer (PCa) and type 2 diabetes mellitus (T2DM) are prevalent conditions that often occur concomitantly. However, many aspects of the impact of T2DM, particularly the duration of T2DM and antidiabetic medications, on PCa risk are poorly understood., Methods: To assess the association of duration of T2DM and antidiabetic medication with PCa risk, we designed a matched case-control study, including 31,415 men with PCa and 154,812 PCa-free men in Prostate Cancer data Base Sweden (PCBaSe) 4.1., Results: Overall, a decreased risk of PCa was observed for men with T2DM (odds ratio (OR): 0.81, 95% confidence interval (CI): 0.78-0.84), as compared to men without T2DM. The decreased risk of PCa was consistently showed across duration of T2DM. With respect to use of antidiabetic drugs, this inverse association with duration was also found for all medications types, as compared to men without T2DM, including insulin, metformin and sulphonylurea (SU) (e.g. 3- < 5 yr insulin OR:0.69, 95%CI:0.60-0.80; 3- < 5 yr metformin OR: 0.82, 95%CI: 0.74-0.91; 3- < 5 yr SU OR: 0.72, 95%CI: 0.62-0.83). When stratifying by PCa risk categories, this decreased risk was most evident for diagnosis of low and intermediate-risk PCa (low-risk OR: 0.65, 95%CI: 0.66-0.70, intermediate-risk OR: 0.80, 95%CI: 0.75-0.85)., Conclusions: The study showed an inverse association between pre-existing T2DM and PCa across different durations of T2DM and all types of T2DM medication received. This inverse association was most evident for low- and intermediate-risk PCa, suggesting that whilst T2DM and its medication may protect some men from developing PCa, the relationship warrants further study.

Prostate Cancer Diagnosis and Treatment Enhancement Through the Power of Big Data in Europe (PIONEER) is a European network of excellence for big data in prostate cancer, consisting of 32 private and public stakeholders from 9 countries across Europe. Launched by the Innovative Medicines Initiative 2 and part of the Big Data for Better Outcomes Programme (BD4BO), the overarching goal of PIONEER is to provide high-quality evidence on prostate cancer management by unlocking the potential of big data. The project has identified critical evidence gaps in prostate cancer care, via a detailed prioritization exercise including all key stakeholders. By standardizing and integrating existing high-quality and multidisciplinary data sources from patients with prostate cancer across different stages of the disease, the resulting big data will be assembled into a single innovative data platform for research. Based on a unique set of methodologies, PIONEER aims to advance the field of prostate cancer care with a particular focus on improving prostate-cancer-related outcomes, health system efficiency by streamlining patient management, and the quality of health and social care delivered to all men with prostate cancer and their families worldwide.

Background: Given the growing importance of patient-reported outcomes (PROs) as part of "big data" in improving patient care, there is a need to provide a state-of-the-art picture of the added value of using PROs in prostate cancer (PCa) randomized controlled trials (RCTs). We aimed to synthetize the most recent high-quality PRO evidence-based knowledge from PCa RCTs and to examine whether quality of PRO reporting in PCa research improved over time., Methods: We conducted a systematic literature search using PubMed, from April 2012 until February 2019. For benchmarking purposes, we also included RCTs identified in our previously published review of RCTs (2004-2012). Methodology for study identification and evaluation followed standardized criteria and a predefined data extraction form was used to abstract information. PRO quality of the studies was evaluated using the International Society of Quality of Life Research (ISOQOL) recommended criteria., Results: A total of 55 new RCTs were published between April 2012 and February 2019. About 24 (43.6%) RCTs were found to be of high-quality regarding PRO assessments. Of these, 13 (54.2%) have been reported in the most recent European Association of Urology (EAU) PCa Guidelines. Overall QoL and sexual, urinary, and bowel function were the most commonly reported PROs. FACT-P, EPIC-26, and EORTC QLQ-C30 and/or its module PR25 were most frequently used as measurement tools. An overall improvement in the completeness of PRO reporting was noted over time., Conclusion: Many PRO trials are currently not included in the EAU guidelines. Our findings suggest that there has to be a better consensus on the use of PRO data for PCa patients, which will then be reflected in the PCa Guidelines and future data collection. Homogeneity in PROs collection and measurement tools will in turn enable "big data" Consortia to increase the patients' voice in clinical research., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Fatty acid synthase (FASN) is commonly overexpressed in prostate cancer and associated with tumour progression. FASN is responsible for de novo synthesis of the fatty acid palmitate; the building block for protein palmitoylation. Recent work has suggested that alongside its established role in promoting cell proliferation FASN may also promote invasion. We now find depletion of FASN expression increases prostate cancer cell adhesiveness, impairs HGF-mediated cell migration and reduces 3D invasion. These changes in motility suggest that FASN can mediate actin cytoskeletal remodelling; a process known to be downstream of Rho family GTPases. Here, we demonstrate that modulation of FASN expression specifically impacts on the palmitoylation of the atypical GTPase RhoU. Impaired RhoU activity in FASN depleted cells leads to reduced adhesion turnover downstream of paxillin serine phosphorylation, which is rescued by addition of exogenous palmitate. Moreover, canonical Cdc42 expression is dependent on the palmitoylation status of RhoU. Thus we uncover a novel relationship between FASN, RhoU and Cdc42 that directly influences cell migration potential. These results provide compelling evidence that FASN activity directly promotes cell migration and supports FASN as a potential therapeutic target in metastatic prostate cancer.

Aim: Gonadotropin-releasing hormone (GnRH) agonists are used to treat men with prostate cancer (PCa). To date, no study has fully assessed patterns of adherence to GnRH agonists. We investigated patterns of adherence to GnRH agonists using data from Prostate Cancer data Base Sweden (PCBaSe). Methods: PCBaSe links the National Prostate Cancer Register (NPCR) Sweden to other healthcare registers and demographic databases. Men on primary or secondary GnRH agonists between 2006-2013 entered the study 45 days after GnRH agonists' initiation (run-in period) and exited at 3 years. Medication possession ratio quantified adherents (≥80%). Multivariable logistic regression models included age, injection interval, PCa risk categories, Charlson Comorbidity Index, prior PCa treatment, civil status and year of GnRH initiation. Odds ratios (OR) and 95% confidence intervals (CI) expressed odds of adherence. Results: Men on primary GnRH agonists ( n  = 8,105) were more adherent with increasing age (75-84 years compared to ≤65 years OR: 1.49; 95% CI: 1.23-1.81), longer injection intervals (365 days compared to 90 days OR: 3.29; 95% CI: 2.52-4.30) and higher PCa risk categories at diagnosis (distant metastasis compared to low risk PCa OR: 3.56; 95% CI: 2.54-5.00). Men on secondary GnRH agonists ( n  = 4,738) were more adherent with increasing age (≥85 years compared to ≤65 years OR: 1.65; 95% CI: 1.23-2.22) and prior PCa treatment (anti-androgens compared to deferred treatment OR: 1.50; 95% CI: 1.23-1.82), (radiotherapy compared to deferred treatment OR: 1.35; 95% CI: 1.11-1.64). Conclusions: Longer injection intervals could be addressed in the clinical setting to improve adherence.

Background: Active surveillance (AS) enrolment criteria and follow-up schedules for low-risk prostate cancer vary between institutions. However, uncertainty remains about adherence to these protocols., Objective: To determine adherence to institution-specific AS inclusion criteria and follow-up schedules within the Movember Foundation's Global Action Plan Prostate Cancer Active Surveillance (GAP3) initiative., Design, Setting, and Participants: We retrospectively assessed the data of 15 101 patients from 25 established AS cohorts worldwide between 2014 and 2016., Outcome Measurements and Statistical Analysis: Adherence to individual AS inclusion criteria was rated on a five-point Likert scale ranging from poor to excellent. Nonadherence to follow-up schedules was defined as absence of repeat biopsy 1 yr after the scheduled date. Cohorts were pooled into annual and Prostate Cancer Research International: Active Surveillance (PRIAS)-based biopsy schedules, and a generalised linear mixed model was constructed to test for nonadherence., Results and Limitations: Serum prostate-specific antigen (PSA) inclusion criteria were followed in 92%, Gleason score (GS) criteria were followed in 97%, and the number of positive biopsy cores was followed in 94% of men. Both age and tumour stage (T stage) criteria had 99% adherence overall. Pooled nonadherence rates increased over time-8%, 16%, and 34% for annual schedules and 11%, 30%, and 29% for PRIAS-based schedules at 1, 4, and 7 yr, respectively-and did not differ between biopsy schedules. A limitation is that our results do not consider the use of multiparametric magnetic resonance imaging., Conclusions: In on-going development of evidence-based AS protocols, variable adherence to PSA and GS inclusion criteria should be considered. Repeat biopsy adherence reduces with increased duration of surveillance, independent of biopsy frequency. This emphasises the importance of risk stratification at the commencement of AS., Patient Summary: We studied adherence to active surveillance protocols for prostate cancer worldwide. We found that inclusion criteria were generally followed well, but adherence to repeat biopsy reduced with time. This should be considered when optimising future active surveillance protocols., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: Existing research indicates that moderate-to-vigorous physical activity (PA) alleviates treatment side effects and is associated with survival in men with prostate cancer. We aimed to ascertain the state of research investigating barriers and facilitators to PA in men with prostate cancer and synthesise existing qualitative research on this topic., Methods: A systematic review of qualitative and quantitative studies was conducted. MEDLINE, Embase, PsycINFO, Web of Knowledge, CINAHL, PEDro, OATD, and WorldCat were searched to June 2019 for quantitative studies investigating causes or predictors of PA or qualitative studies describing patient-reported barriers/facilitators to PA, amongst men with prostate cancer of any stage. Thirty-two studies (n = 17 quantitative; n = 15 qualitative) were included from 3698 screened articles., Results: Heterogeneity and unsystematic reporting of quantitative study methods prohibited a quantitative data synthesis. Thematic synthesis of qualitative studies produced five analytical themes: individual needs by treatment pathway, self-determination and its relationship with prostate cancer-related events, co-ordination and support of the clinical care team, individual preferences in discrete aspects of PA engagement style, and the potential for a bidirectional facilitative relationship between structured group PA and spontaneous peer support. Both qualitative and quantitative studies indicated incontinence as a barrier., Conclusions: Unsystematic reporting of interventions hinders a robust quantitative understanding of behavioural intervention research in this subject area. Good co-ordination of multidisciplinary care personnel could facilitate PA, by enabling a more comprehensive approach to targeting social cognitive processes. Well-timed intervention and access to highly individualised PA support, including optional group PA classes, seem to also be important facilitators., (© 2019 John Wiley & Sons, Ltd.)

Importance: Diabetic men appear to have a lower risk of prostate cancer. Whether antidiabetic medications are protective or potentially mask prostate cancer by lowering prostate-specific antigen (PSA) levels is unclear., Objective: To examine the associations of antidiabetic medication use with (1) PSA levels, (2) frequency of PSA testing, (3) receipt of biopsy following elevated PSA results, and (4) prostate cancer detection at biopsy., Design, Setting, and Participants: Population-based cohort study using data from the Stockholm PSA and Biopsy Register. Participants were all prostate cancer-free men aged 40 to 79 years residing in Stockholm County, Sweden, between January 1, 2006, and December 31, 2015. Data were analyzed from November 2018 to March 2019., Exposures: One or more prescription for metformin, sulfonylurea, or insulin, as recorded in Sweden's National Prescribed Drug Register., Main Outcomes and Measures: Levels of PSA following first exposure to antidiabetic medications were assessed using multivariable linear regression. Frequency of PSA testing was assessed via multivariable Poisson regression. Biopsy following elevated PSA (≥3.0 ng/mL) and prostate cancer detection at biopsy were assessed via multivariable logistic regression., Results: The cohort of 564 666 men (median [range] age, 65 [40-79] years) consisted of 4583 men initially exposed to metformin, 1104 exposed to sulfonylurea, and 978 exposed to insulin who were age matched with unexposed men (1:5). Exposed men had lower median (interquartile range) PSA levels before starting antidiabetic medications compared with unexposed men (1.2 [0.7-2.5] vs 1.6 [0.8-3.2] ng/mL). After accounting for baseline differences, PSA levels did not vary from those of unexposed men following exposure to antidiabetic medications. Frequency of PSA testing was higher for those receiving metformin (rate ratio, 1.07; 95% CI, 1.06-1.09) and sulfonylurea (rate ratio, 1.06; 95% CI, 1.03-1.08) but was lower for those receiving insulin (rate ratio, 0.79; 95% CI, 0.77- 0.81). Likelihood of biopsy after elevated PSA was lower among men receiving metformin (odds ratio, 0.87; 95% CI, 0.80-0.96) and insulin (odds ratio, 0.83; 95% CI, 0.74-0.93). There were no differences in prostate cancer detection at biopsy, regardless of PSA levels that triggered the biopsy., Conclusions and Relevance: This study's findings do not support the hypothesis that the inverse association between diabetes and prostate cancer is mediated through antidiabetic medications lowering PSA levels to mask prostate cancer. They do suggest potential detection bias due to fewer biopsies among men receiving antidiabetic medications, which may explain the lower prostate cancer risk in men with diabetes.

Introduction: Overtreatment of localised prostate cancer is substantial despite increased use of active surveillance. No randomised trials help define how to monitor patients or when to initiate treatment with curative intent., Methods and Analysis: A randomised, multicentre, intervention trial designed to evaluate the safety of an MRI-based active surveillance protocol, with standardised triggers for repeated biopsies and radical treatment. The aim is to reduce overtreatment of prostate cancer. 2000 men will be randomly allocated to either surveillance according to current practice or to standardised triggers at centres in Sweden, Norway, Finland and the UK. Men diagnosed in the past 12 months with prostate cancer, ≤T2a, prostate-specific antigen (PSA) <15 ng/mL, PSA density ≤0.2 ng/mL/cc, any International Society of Urological Pathology (ISUP) grade 1 are eligible. Men with ISUP grade 2 in <30% of cores on systematic biopsy and <10 mm cancer in one core on systematic or targeted biopsy are also eligible. Men diagnosed on systematic biopsy should have an MRI and targeted biopsies against Prostate Imaging and Reporting Data System V.2 3-5 lesions before inclusion. Identical follow-up in the two study arms: biannual PSA testing, yearly clinical examination and MRI every second year. In the experimental arm, standardised triggers based on MRI and PSA density elicit repeated biopsies. MRI and histopathological progression trigger radical treatment. Primary outcome measure is progression-free survival. Secondary outcome measures are cumulative incidence of metastatic disease, treatments with curative intent, pT3-4 at radical prostatectomy, switch to watchful waiting, prostate cancer mortality and quality of life. Inclusion started in October 2016 and in October 2018; 275 patients have been enrolled., Ethics and Dissemination: Ethical approval was obtained in each participating country. Results for the primary and secondary outcome measures will be submitted for publication in peer-reviewed journals., Trial Registration Number: NCT02914873., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Patient-related factors such as concern about cancer are believed to influence both men's decisions to undergo prostate specific antigen (PSA) testing and to have definitive treatment if diagnosed with low risk prostate cancer (PCa). The potential link between screening frequency and choice of active surveillance (AS) for low risk disease has not been studied previously. Our aim was to investigate whether there is any association between PCa screening frequency or previous negative prostate biopsy and uptake of AS among men with low risk PCa., Methods: This register-based study included all men ≤75 years from Stockholm who were diagnosed with low risk PCa from 2008 to 2014 (n = 4336). Pre-diagnostic PSA testing and biopsy histories were obtained from the Stockholm PSA and Biopsy Register, a population-based register for the Stockholm country. The association between previous screening/biopsy history and AS uptake (based on primary treatment recorded in the National Prostate Cancer Register) was examined using multivariable logistic regression., Results: Forty seven percent of men with low risk PCa underwent AS. Uptake was associated with older age, very low risk disease, more recent diagnosis and absence of family history. None of the screening/biopsy measures (testing frequency, mean interval, PSA velocity, highest pre-diagnostic PSA or prior negative biopsy) were associated with uptake of AS among men with low risk PCa. Generalisability to settings with different policies and practices may be limited., Conclusion: We found no evidence that screening frequency and negative biopsy influence uptake of AS among Swedish men with low risk PCa. Further research is required to determine factors that still present barriers for men taking up AS.

One of the more recently investigated adverse long-term side effects of gonadotropin-releasing hormone (GnRH) agonists for prostate cancer (PCa) is cardiovascular disease (CVD). Studies suggest lower risk of CVD following GnRH antagonists (degarelix) than GnRH agonists. This protocol describes precise codes used to extract variables from five European databases for a study that compares risk of CVD following GnRH agonists and antagonists for PCa. PCa men on primary GnRH agonists or antagonists were identified from the UK THIN (The Health Improvement Network) database, National Health Service (NHS) Scotland, Belgian Cancer Registry (BCR), Dutch PHARMO Database Network and French National Database (SNIIRAM). Cohort entry was defined as date of treatment initiation. CVD event was defined as any first incident or fatal CVD after cohort entry. Readcodes in THIN and ICD codes in NHS Scotland, BCR, PHARMO and SNIIRAM were used to extract variables. Risk of Bias in Non-randomised studies of Interventions (ROBINS-I) tool was used to assess the potential risk of biases in this study. 51 572 men with a median follow-up time of 2 years started on GnRH agonists and 2 417 men with a median follow-up time of 1 year started on GnRH antagonists between 2010 and 2017 in the UK, Scotland, Belgium, the Netherlands and France. Data from five countries improved the study power and internal validity required to compare risk of CVD between GnRH agonists and antagonists, the latter being a fairly new drug with limited data in individual countries., (© 2019 The Authors. Fundamental & Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of Société Françaisede Pharmacologie et de Thérapeutique.)

Background: Researchers remain divided on the major causes of dropout from active surveillance (AS), with rates of up to 38% among men with no evidence of prostate cancer (PC) progression., Objective: To develop and evaluate an educational intervention in terms of adherence to AS among men with low- to intermediate-risk PC., Design, Setting, and Participants: We first carried out focus group discussions with men who had remained on and dropped out of AS to inform an intervention to increase adherence to AS. A total of 255 consecutive men who had selected AS were then recruited to either standard care (written information and access to a nurse specialist) or standard care and the intervention., Intervention: An educational seminar was designed by patients and clinicians including information on imaging, biopsy techniques, understanding pathology, large AS cohorts - mortality and morbidity risk and diet and lifestyle advice., Outcome Measurements and Statistical Analysis: The proportion of men dropping out of AS for reasons other than disease progression was assessed at 1 and 5yr after AS selection using multivariate logistic regression., Results and Limitations: Common themes influencing decision-making by men on AS were identified: (1) clinical consistency; (2) information; and (3) lifestyle advice. Addition of an educational seminar led to significantly fewer men dropping out of AS: at 1 and 5yr the dropout rate was 25% and 42%, respectively, in the standard care group, compared to 11% and 22% (p=0.001) in the intervention group. In the intervention group, 18 men failed to attend the seminar., Conclusions: The AS dropout rate was halved following a single educational seminar delivered to groups of men with intermediate- or low-risk PC, even at 5yr., Patient Summary: Men on active surveillance (AS) for prostate cancer feel more supported when provided with an educational seminar within 3 mo of their treatment choice. The seminar halved the number of men dropping-out of AS, even at 5yr., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: To study whether androgen deprivation therapy (ADT), the mainstay treatment for advanced and disseminated prostate cancer, is associated with risk of dementia., Methods: Risk of dementia in men with prostate cancer primarily managed with ADT or watchful waiting (WW) in the Prostate Cancer Database Sweden, PCBaSe, was compared with that in prostate cancer-free men, matched on birth year and county of residency. We used Cox regression to calculate the hazard ratios (HRs) for Alzheimer's and non-Alzheimer's dementia (vascular dementia, dementia secondary to other diseases or unspecified dementias) for different types and duration of ADT and oral antiandrogens (AAs) as well as for men managed with WW., Results: A total of 25 967 men with prostate cancer and 121 018 prostate cancer-free men were followed for a median of 4 years. In both groups 6% of the men were diagnosed with dementia. In men with prostate cancer, gonadotropin-releasing hormone agonist treatment ( HR 1.15, 95% confidence interval [CI] 1.07-1.23) and orchiectomy (HR 1.60, 95% CI 1.32-1.93) were associated with an increased risk of dementia, as compared to no treatment in prostate cancer-free men; however, this increase in risk was only observed for non-Alzheimer's dementia and occurred from year 1-4 after start of ADT. No increase in risk for any type of dementia was observed for men treated with AAs or for men on WW., Conclusion: This population-based cohort study does not support previous observations of an increased risk of Alzheimer's dementia for men on ADT; however, there was a small increase in risk of non-Alzheimer's dementia., (© 2019 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background: Whether chronic inflammation increases prostate cancer risk remains unclear. This study investigated whether chronic inflammatory diseases (CID) or anti-inflammatory medication use (AIM) were associated with prostate cancer risk., Methods: Fifty-five thousand nine hundred thirty-seven cases (all prostate cancer, 2007-2012) and 279,618 age-matched controls were selected from the Prostate Cancer Database Sweden. CIDs and AIMs was determined from national patient and drug registers. Associations were investigated using conditional logistic regression, including for disease/drug subtypes and exposure length/dose., Results: Men with a history of any CID had slightly increased risk of any prostate cancer diagnosis (OR: 1.08; 95%CI: 1.04-1.12) but not 'unfavourable' (high-risk or advanced) prostate cancer. Generally, risk of prostate cancer was highest for shorter exposure times. However, a positive association was observed for asthma > 5 years before prostate cancer diagnosis (OR: 1.21; 95%CI: 1.05-1.40). Risk of prostate cancer was increased with prior use of any AIMs (OR: 1.26; 95%CI: 1.24-1.29). A positive trend with increasing cumulative dose was only observed for inhaled glucocorticoids (p < 0.011)., Conclusion: Detection bias most likely explains the elevated risk of prostate cancer with prior history of CIDs or use of AIMs, given the higher risk immediately after first CID event and lack of dose response. However, findings for length of time with asthma and dose of inhaled glucocorticoids suggest that asthma may increase risk of prostate cancer through other pathways.