Summary Paper on Underactive Bladder from the European Association of Urology Guidelines on Non-neurogenic Male Lower Urinary Tract Symptoms.

Background And Objective: The European Association of Urology (EAU) Guidelines Panel on non-neurogenic male lower urinary tract symptoms (LUTS) aimed to develop a new subchapter on underactive bladder (UAB) in non-neurogenic men to inform health care providers of current best evidence and practice. Here, we present a summary of the UAB subchapter that is incorporated into the 2024 version of the EAU guidelines on non-neurogenic male LUTS.

Methods: A systematic literature search was conducted from 2002 to 2022, and articles with the highest certainty evidence were selected.

Rational evolution for altering the ligand preference of estrogen receptor alpha.

Estrogen receptor α is commonly used in synthetic biology to control the activity of genome editing tools. The activating ligands, estrogens, however, interfere with various cellular processes, thereby limiting the applicability of this receptor. Altering its ligand preference to chemicals of choice solves this hurdle but requires adaptation of unspecified ligand-interacting residues.

The Prevalence of Lower Limb and Genital Lymphedema after Prostate Cancer Treatment: A Systematic Review.

(1) Background: Secondary lymphedema is a chronic, progressive, and debilitating condition with an important impact on quality of life. Lymphedema is a frequently reported complication in oncological surgery but has not been systematically studied in the setting of prostate cancer. (2) Methods: Pubmed/MEDLINE and Embase were systematically searched to identify articles reporting on lower limb or genital lymphedema after primary treatment (surgery of radiation therapy) of the prostate and the pelvic lymph nodes in men with prostate cancer.

N/C Interactions Are Dispensable for Normal In Vivo Functioning of the Androgen Receptor in Male Mice.

The androgen receptor (AR) plays a central role in the development and maintenance of the male phenotype. The binding of androgens to the receptor induces interactions between the carboxyterminal ligand-binding domain and the highly conserved 23FQNLF27 motif in the aminoterminal domain. The role of these so-called N/C interactions in AR functioning is debated.

A disease-associated missense mutation in CYP4F3 affects the metabolism of leukotriene B4 via disruption of electron transfer.

Background: Cytochrome P450 4F3 (CYP4F3) is an ω-hydroxylase that oxidizes leukotriene B4 (LTB4), prostaglandins, and fatty acid epoxides. LTB4 is synthesized by leukocytes and acts as a chemoattractant for neutrophils, making it an essential component of the innate immune system. Recently, involvement of the LTB4 pathway was reported in various immunological disorders such as asthma, arthritis, and inflammatory bowel disease.

Genomic Features of Lung-Recurrent Hormone-Sensitive Prostate Cancer.

Purpose: Pulmonary involvement is rare in metastatic hormone-sensitive prostate cancer (mHSPC) that recurs after treatment for localized disease. Guidelines recommend intensive systemic therapy, similar to patients with liver metastases, but some lung-recurrent mHSPC may have good outcomes. Genomic features of lung metastases may clarify disease aggression, but are poorly understood since lung biopsy is rarely performed.

Diagnostic and prognostic factors in patients with prostate cancer: a systematic review.

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.

Updating and Integrating Core Outcome Sets for Localised, Locally Advanced, Metastatic, and Nonmetastatic Castration-resistant Prostate Cancer: An Update from the PIONEER Consortium.

Context: Harmonisation of outcome reporting and definitions for clinical trials and routine patient records can enable health care systems to provide more efficient outcome-driven and patient-centred interventions. We report on the work of the PIONEER Consortium in this context for prostate cancer (PCa).

Objective: To update and integrate existing core outcome sets (COS) for PCa for the different stages of the disease, assess their applicability, and develop standardised definitions of prioritised outcomes.

Antizyme Inhibitor 1 Regulates Matrikine Expression and Enhances the Metastatic Potential of Aggressive Primary Prostate Cancer.

Unlabelled: Molecular drivers of metastasis in patients with high-risk localized prostate cancer are poorly understood. Therefore, we aim to study molecular drivers of metastatic progression in patients with high-risk prostate cancer. A retrospective matched case-control study of two clinico-pathologically identical groups of patients with high-risk prostate cancer was undertaken.

Systematic Review of Active Surveillance for Clinically Localised Prostate Cancer to Develop Recommendations Regarding Inclusion of Intermediate-risk Disease, Biopsy Characteristics at Inclusion and Monitoring, and Surveillance Repeat Biopsy Strategy.

Context: There is uncertainty regarding the most appropriate criteria for recruitment, monitoring, and reclassification in active surveillance (AS) protocols for localised prostate cancer (PCa).

Objective: To perform a qualitative systematic review (SR) to issue recommendations regarding inclusion of intermediate-risk disease, biopsy characteristics at inclusion and monitoring, and repeat biopsy strategy.

Evidence Acquisition: A protocol-driven, Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-adhering SR incorporating AS protocols published from January 1990 to October 2020 was performed.

Small-molecule profiling for steroid receptor activity using a universal steroid receptor reporter assay.

A critical step in the development of novel drug candidates for the treatment of steroid related diseases is ensuring the absence of crosstalk with steroid receptors (SRs). Establishing this SR cross-reactivity profile requires multiple reporter assays as each SR associates with its unique enhancer region, a labor intensive and time-consuming approach. To overcome this need for multi-reporter assays, we established a steroid receptor inducible luciferase reporter assay (SRi-Luc) that allows side-by-side examination of agonistic and antagonistic properties of small-molecules on all steroid receptors.

The androgen receptor depends on ligand-binding domain dimerization for transcriptional activation.

Whereas dimerization of the DNA-binding domain of the androgen receptor (AR) plays an evident role in recognizing bipartite response elements, the contribution of the dimerization of the ligand-binding domain (LBD) to the correct functioning of the AR remains unclear. Here, we describe a mouse model with disrupted dimerization of the AR LBD (AR ). The disruptive effect of the mutation is demonstrated by the feminized phenotype, absence of male accessory sex glands, and strongly affected spermatogenesis, despite high circulating levels of testosterone.

The Key Role of Patient Involvement in the Development of Core Outcome Sets in Prostate Cancer.

Patients are the stewards of their own care and hence their voice is important when designing and implementing research. Patients should be involved not only as participants in research that impacts their care, as the recipients of that care and any associated harms, but also as research collaborators in prioritising important questions from the patient perspective and designing the research and the ways in which is it most appropriate to involve patients. The PIONEER Consortium, an international multistakeholder collaboration lead by the European Association of Urology, has developed a core outcome set (COS) for localised and metastatic prostate cancer relevant to all stakeholders in particular patients.

Neoadjuvant hormonal therapy before radical prostatectomy in high-risk prostate cancer.

Patients with high-risk prostate cancer treated with curative intent are at an increased risk of biochemical recurrence, metastatic progression and cancer-related death compared with patients treated for low-risk or intermediate-risk disease. Thus, these patients often need multimodal therapy to achieve complete disease control. Over the past two decades, multiple studies on the use of neoadjuvant treatment have been performed using conventional androgen deprivation therapy, which comprises luteinizing hormone-releasing hormone agonists or antagonists and/or first-line anti-androgens.

Evaluation of Oncological Outcomes and Data Quality in Studies Assessing Nerve-sparing Versus Non-Nerve-sparing Radical Prostatectomy in Nonmetastatic Prostate Cancer: A Systematic Review.

Context: Surgical techniques aimed at preserving the neurovascular bundles during radical prostatectomy (RP) have been proposed to improve functional outcomes. However, it remains unclear if nerve-sparing (NS) surgery adversely affects oncological metrics.

Objective: To explore the oncological safety of NS versus non-NS (NNS) surgery and to identify factors affecting the oncological outcomes of NS surgery.

Patient- and Tumour-related Prognostic Factors for Urinary Incontinence After Radical Prostatectomy for Nonmetastatic Prostate Cancer: A Systematic Review and Meta-analysis.

Context: While urinary incontinence (UI) commonly occurs after radical prostatectomy (RP), it is unclear what factors increase the risk of UI development.

Objective: To perform a systematic review of patient- and tumour-related prognostic factors for post-RP UI. The primary outcome was UI within 3 mo after RP.

A Systematic Review of the Impact of Surgeon and Hospital Caseload Volume on Oncological and Nononcological Outcomes After Radical Prostatectomy for Nonmetastatic Prostate Cancer.

Context: The impact of surgeon and hospital volume on outcomes after radical prostatectomy (RP) for localised prostate cancer (PCa) remains unknown.

Objective: To perform a systematic review on the association between surgeon or hospital volume and oncological and nononcological outcomes following RP for PCa.

Evidence Acquisition: Medline, Medline In-Process, Embase, and the Cochrane Central Register of Controlled Trials were searched.

Diagnostic and prognostic factors in patients with prostate cancer: a systematic review protocol.

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.

Comparison of postoperative complications of ileal conduits versus orthotopic neobladders.

Background: Radical cystectomy (RC) and urinary diversion (UD), with either an ileal conduit (IC) or an orthotopic neobladder (NB), is a complex surgery, in which various complications can occur. In this study, we compared postoperative complication rates after a RC and UD performed for the treatment of muscle-invasive bladder cancer or recurring high-risk non-muscle-invasive bladder cancer in our center.

Methods: We retrospectively included 604 patients that underwent UDs from December 1996 to August 2015.

A Systematic Review of Focal Ablative Therapy for Clinically Localised Prostate Cancer in Comparison with Standard Management Options: Limitations of the Available Evidence and Recommendations for Clinical Practice and Further Research.

Context: The clinical effectiveness of focal therapy (FT) for localised prostate cancer (PCa) remains controversial.

Objective: To analyse the evidence base for primary FT for localised PCa via a systematic review (SR) to formulate clinical practice recommendations.

Evidence Acquisition: A protocol-driven, PRISMA-adhering SR comparing primary FT (sub-total, focal, hemi-gland, or partial ablation) versus standard options (active surveillance [AS], radical prostatectomy [RP], or external beam radiotherapy [EBRT]) was undertaken.

Current and emerging therapies for localized high-risk prostate cancer.

: Despite progress in the field of high-risk localized prostate cancer (HRPCa) treatments, high-risk patients treated with curative intent are at increased risk of biochemical recurrence, metastatic progression and cancer-related death. The optimal treatment strategy remains a topic of debate. This review provides an overview of the current and investigational therapeutic options for HRPCa.

Clinical Actionability of the Genomic Landscape of Metastatic Castration Resistant Prostate Cancer.

The development of targeted therapies increases treatment options for metastatic castration resistant prostate cancer (mCRPC) patients. There is a need for strong predictive and prognostic signatures to guide physicians in treating mCRPC patients. In this review we unravel the possible actionability in the AR pathway, PI3K AKT signaling, and DNA repair pathways.

EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer-2020 Update. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent.

Objective: To present a summary of the 2020 version of the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Geriatric Oncology (SIOG) guidelines on screening, diagnosis, and local treatment of clinically localised prostate cancer (PCa).

Evidence Acquisition: The panel performed a literature review of new data, covering the time frame between 2016 and 2020. The guidelines were updated and a strength rating for each recommendation was added based on a systematic review of the evidence.

EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer. Part II-2020 Update: Treatment of Relapsing and Metastatic Prostate Cancer.

Objective: To present a summary of the 2020 version of the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy & Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Geriatric Oncology (SIOG) guidelines on the treatment of relapsing, metastatic, and castration-resistant prostate cancer (CRPC).

Evidence Acquisition: The working panel performed a literature review of the new data (2016-2019). The guidelines were updated, and the levels of evidence and/or grades of recommendation were added based on a systematic review of the literature.