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Abstract Context Empiric use of medical and nutritional supplements to improve semen parameters and pregnancy rates in couples with idiopathic infertility has reached global proportions, although the evidence base for their use in this setting is controversial. Objective We systematically reviewed evidence comparing the benefits of nutritional and medical therapy on pregnancy rates and semen parameters in men with idiopathic infertility. Evidence acquisition A literature search was performed using MEDLINE, Embase, LILACS, and the Cochrane Library (searched from January 1, 1990 to September 19, 2017). using the methods detailed in the Cochrane Handbook. Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess the certainty of evidence. Evidence synthesis The literature search identified 5663 citations, and after screening of abstracts and full texts, 61 studies (59 randomised controlled trials and two nonrandomised comparative studies) were included. Pooled results demonstrated that pentoxyfylline, coenzyme Q10, L-carnitine, follicle-stimulating hormone, tamoxifen, and kallikrein all resulted in improvements in semen parameters. Individual studies identified several other medical and nutritional therapies that improved semen parameters, but data were limited to individual studies with inherent methodological flaws. There were limited data available on live birth and pregnancy rates for all interventions. The GRADE certainty of evidence for all outcomes was very low mainly owing to methodological flaws and inconsistencies in study design. Some outcomes were also downgraded owing to imprecision of results. Conclusions There is some evidence that empiric medical and nutritional supplements may improve semen parameters. There is very limited evidence that empiric therapy leads to better live birth rates, spontaneous pregnancy, or pregnancy following assisted-reproductive techniques. However, the findings should be interpreted with caution as there were some methodological flaws, as a number of studies were judged to be either at high or unclear risk of bias for many domains. Patient summary This review identified several medical and nutritional treatments, such as pentoxyfylline, coenzyme Q10, L-carnitine, follicle-stimulating hormone, tamoxifen, and kallikrein, that appear to improve semen parameters. However, there are limited data suggesting improvements in pregnancy and live birth rates. The lack of evidence can be attributed to methodological flaws in studies and the low number of pregnancies reported. Take Home Message This systematic review indicates that medical treatment and nutritional supplementation may improve male fertility. There is some evidence that empiric therapy may lead to improved rates of live birth, spontaneous pregnancy, and pregnancy following assisted reproductive techniques. [ABSTRACT FROM AUTHOR]

Context The findings of systematic reviews (SRs) and meta-analyses (MAs) are used for clinical decision making. The European Association of Urology has committed increasing resources into the development of high quality clinical guidelines based on such SRs and MAs. Objective In this paper, we have summarised the process of conducting SRs for underpinning clinical practice guidelines under the auspices of the European Association of Urology Guidelines Office. Evidence acquisition The process involves explicit methods and the findings should be reproducible. When conducting a SR, the essential first step is to formulate a clear and answerable research question. An extensive literature search lays the foundation for evidence synthesis. Data are extracted independently by two reviewers and any disagreements are resolved by discussion or arbitration by a third reviewer. Evidence synthesis In SRs, data for particular outcomes in individual randomised controlled trials may be combined statistically in a meta-analysis to increase power when the studies are similar enough. Biases in studies included in a SR/MA can lead to either an over estimation or an under estimation of true intervention effect size, resulting in heterogeneity in outcome between studies. A number of different tools are available such as Cochrane Risk of Bias assessment tool for randomised controlled trials. In circumstances where there is too much heterogeneity, or when a review has included nonrandomised comparative studies, it is more appropriate to conduct a narrative synthesis . The GRADE tool for assessing quality of evidence strives to be a structured and transparent system, which can be applied to all evidence, regardless of quality. A SR not only identifies, evaluates, and summarises the best available evidence, but also the gaps to be targeted by future studies. Conclusions SRs and MAs are integral in developing sound clinical practice guidelines and recommendations. Patient summary Clinical practice guidelines should be evidence based, and systematic reviews and meta-analyses are essential in their production. We have discussed the key steps of conducting systematic reviews and meta-analyses in this paper. [ABSTRACT FROM AUTHOR]

The transperineal approach is preferred to reduce prostate biopsy (PB)-related infections. Fluoroquinolones are suspended for prophylaxis of PB in the European Union; therefore, alternative antibiotics based on local resistance, or targeted prophylaxis, in conjunction with povidone-iodine rectal preparation are recommended for transrectal PB. [ABSTRACT FROM AUTHOR]

The optimal treatment for men with high-risk localized or locally advanced prostate cancer (PCa) remains unknown. To perform a systematic review of the existing literature on the effectiveness of the different primary treatment modalities for high-risk localized and locally advanced PCa. The primary oncological outcome is the development of distant metastases at ≥5 yr of follow-up. Secondary oncological outcomes are PCa-specific mortality, overall mortality, biochemical recurrence, and need for salvage treatment with ≥5 yr of follow-up. Nononcological outcomes are quality of life (QoL), functional outcomes, and treatment-related side effects reported. Medline, Medline In-Process, Embase, and the Cochrane Central Register of Randomized Controlled Trials were searched. All comparative (randomized and nonrandomized) studies published between January 2000 and May 2019 with at least 50 participants in each arm were included. Studies reporting on high-risk localized PCa (International Society of Urologic Pathologists [ISUP] grade 4–5 [Gleason score {GS} 8–10] or prostate-specific antigen [PSA] >20 ng/ml or ≥ cT2c) and/or locally advanced PCa (any PSA, cT3–4 or cN+, any ISUP grade/GS) or where subanalyses were performed on either group were included. The following primary local treatments were mandated: radical prostatectomy (RP), external beam radiotherapy (EBRT) (≥64 Gy), brachytherapy (BT), or multimodality treatment combining any of the local treatments above (±any systemic treatment). Risk of bias (RoB) and confounding factors were assessed for each study. A narrative synthesis was performed. Overall, 90 studies met the inclusion criteria. RoB and confounding factors revealed high RoB for selection, performance, and detection bias, and low RoB for correction of initial PSA and biopsy GS. When comparing RP with EBRT, retrospective series suggested an advantage for RP, although with a low level of evidence. Both RT and RP should be seen as part of a multimodal treatment plan with possible addition of (postoperative) RT and/or androgen deprivation therapy (ADT), respectively. High levels of evidence exist for EBRT treatment, with several randomized clinical trials showing superior outcome for adding long-term ADT or BT to EBRT. No clear cutoff can be proposed for RT dose, but higher RT doses by means of dose escalation schemes result in an improved biochemical control. Twenty studies reported data on QoL, with RP resulting mainly in genitourinary toxicity and sexual dysfunction, and EBRT in bowel problems. Based on the results of this systematic review, both RP as part of multimodal treatment and EBRT + long-term ADT can be recommended as primary treatment in high-risk and locally advanced PCa. For high-risk PCa, EBRT + BT can also be offered despite more grade 3 toxicity. Interestingly, for selected patients, for example, those with higher comorbidity, a shorter duration of ADT might be an option. For locally advanced PCa, EBRT + BT shows promising result but still needs further validation. In this setting, it is important that patients are aware that the offered therapy will most likely be in the context a multimodality treatment plan. In particular, if radiation is used, the combination of local with systemic treatment provides the best outcome, provided the patient is fit enough to receive both. Until the results of the SPCG15 trial are known, the optimal local treatment remains a matter of debate. Patients should at all times be fully informed about all available options, and the likelihood of a multimodal approach including the potential side effects of both local and systemic treatment. We reviewed the literature to see whether the evidence from clinical studies would tell us the best way of curing men with aggressive prostate cancer that had not spread to other parts of the body such as lymph glands or bones. Based on the results of this systematic review, there is good evidence that both surgery and radiation therapy are good treatment options, in terms of prolonging life and preserving quality of life, provided they are combined with other treatments. In the case of surgery this means including radiotherapy (RT), and in the case of RT this means either hormonal therapy or combined RT and brachytherapy. High-risk and locally advanced prostate cancer (PCa) patients are likely to undergo multimodality treatment. Patients should at all times be fully informed about all available options and the likelihood of a multimodal approach, including the potential side effects of both local and systemic treatment. For high-risk localized and locally advanced PCa, both radical prostatectomy as part as multimodal therapy and external beam radiotherapy (EBRT) + long-term androgen deprivation therapy (ADT) can be recommended as primary treatment. For high-risk localized PCa, EBRT + BT can also be offered despite a less favorable toxicity profile. In selected high-risk PCa patients, a shorter duration of ADT might be considered. Until the results of the SPCG15 trial are known, the optimal local treatment remains a matter of debate. [ABSTRACT FROM AUTHOR]

Background: There is uncertainty in deferred active treatment (DAT) programmes, regarding patient selection, follow-up and monitoring, reclassification, and which outcome measures should be prioritised., Objective: To develop consensus statements for all domains of DAT., Design, Setting, and Participants: A protocol-driven, three phase study was undertaken by the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Association of Urology Section of Urological Research (ESUR)-International Society of Geriatric Oncology (SIOG) Prostate Cancer Guideline Panel in conjunction with partner organisations, including the following: (1) a systematic review to describe heterogeneity across all domains; (2) a two-round Delphi survey involving a large, international panel of stakeholders, including healthcare practitioners (HCPs) and patients; and (3) a consensus group meeting attended by stakeholder group representatives. Robust methods regarding what constituted the consensus were strictly followed., Results and Limitations: A total of 109 HCPs and 16 patients completed both survey rounds. Of 129 statements in the survey, consensus was achieved in 66 (51%); the rest of the statements were discussed and voted on in the consensus meeting by 32 HCPs and three patients, where consensus was achieved in additional 27 statements (43%). Overall, 93 statements (72%) achieved consensus in the project. Some uncertainties remained regarding clinically important thresholds for disease extent on biopsy in low-risk disease, and the role of multiparametric magnetic resonance imaging in determining disease stage and aggressiveness as a criterion for inclusion and exclusion., Conclusions: Consensus statements and the findings are expected to guide and inform routine clinical practice and research, until higher levels of evidence emerge through prospective comparative studies and clinical trials., Patient Summary: We undertook a project aimed at standardising the elements of practice in active surveillance programmes for early localised prostate cancer because currently there is great variation and uncertainty regarding how best to conduct them. The project involved large numbers of healthcare practitioners and patients using a survey and face-to-face meeting, in order to achieve agreement (ie, consensus) regarding best practice, which will provide guidance to clinicians and researchers., (Copyright © 2019. Published by Elsevier B.V.)

Context: Clinicians and treatment guideline developers are faced with a dilemma when the results of a new, large, well-conducted randomized controlled trial (RCT) are in direct conflict with the results of a previous systematic review (SR) and meta-analysis (MA)., Objective: To explore and discuss possible reasons for disagreement in results from SRs/MAs and RCTs and to provide guidance to clinicians and guideline developers for making well-informed treatment decisions and recommendations in the face of conflicting data., Evidence Acquisition: The advantages and limitations of RCTs and SRs/MAs are reviewed. Two practical examples that have a direct bearing on European Association of Urology guidelines on treatment recommendations are discussed in detail to illustrate the points to be considered when conflicts exist between the results of large RCTs and SRs/MAs., Evidence Synthesis: RCTs are the gold standard for providing evidence of the effectiveness of interventions. However, concerns regarding the internal and external validity of an RCT may limit its applicability to clinical practice. SRs/MAs synthesize all evidence related to a given research question, but two urologic examples show that the validity of the results depends on the quality of the individual studies, the clinical and methodological heterogeneity of the studies, and publication bias., Conclusions: Although SRs/MAs can provide a higher level of evidence than RCTs, the quality of the evidence from both RCTs and SRs/MAs should be investigated when their results conflict to determine which source provides the better evidence. Guideline developers should have a well-defined and robust process to assess the evidence from MAs and RCTs when such conflicts exist., Patient Summary: We discuss the advantages and limitations of using data from randomized controlled trials and systematic reviews/meta-analyses in informing clinical practice when there are conflicting results. We provide guidance on how such conflicts should be dealt with by guideline organizations., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)