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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. Only comparative studies with ≥50 patients per arm were included. Primary outcomes included oncological, functional, and quality-of-life outcomes. Risk of bias (RoB) and confounding assessments were undertaken. Eligible SRs were reviewed and appraised (AMSTAR) and ongoing prospective comparative studies were summarised. Evidence synthesis Out of 1119 articles identified, four primary studies (1 randomised controlled trial [RCT] and 3 retrospective studies) recruiting 3961 patients and ten eligible SRs were identified. Only qualitative synthesis was possible owing to clinical heterogeneity. Overall, RoB and confounding were moderate to high. An RCT comparing vascular-targeted focal photodynamic therapy (PDT) with AS found a significantly lower rate of treatment failure at 2 yr with PDT. There were no differences in functional outcomes, although PDT was associated with worse transient adverse events. However, the external validity of the study was contentious. A retrospective study comparing focal HIFU with robotic RP found no significant differences in treatment failure at 3 yr, with focal HIFU having better continence and erectile function recovery. Two retrospective cohort studies using Surveillance, Epidemiology and End Results data compared focal laser ablation (FLA) against RP and EBRT, reporting significantly worse oncological outcomes for FLA. The overall data quality and applicability of the primary studies were limited because of clinical heterogeneity, RoB and confounding, lack of long-term data, inappropriate outcome measures, and poor external validity. Virtually all the SRs identified concluded that there was insufficient high-certainty evidence to make definitive conclusions regarding the clinical effectiveness of FT, with the majority of SRs judged to have a low or critically low confidence rating. Eight ongoing prospective comparative studies were identified. Ways of improving the evidence base are discussed. Conclusions The certainty of the evidence regarding the comparative effectiveness of FT as a primary treatment for localised PCa was low, with significant uncertainties. Until higher-certainty evidence emerges from robust prospective comparative studies measuring clinically meaningful outcomes at long-term time points, FT should ideally be performed within clinical trials or well-designed prospective cohort studies. Patient summary We examined the literature to determine the effectiveness of prostate-targeted treatment compared with standard treatments for untreated localised prostate cancer. There was no strong evidence showing that focal treatment compares favourably with standard treatments; consequently, focal treatment is not recommended for routine standard practice.

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. Evidence synthesis: A risk-adapted strategy for identifying men who may develop PCa is advised, generally commencing at 50 yr of age and based on individualised life expectancy. Risk-adapted screening should be offered to men at increased risk from the age of 45 yr and to breast cancer susceptibility gene (BRCA) mutation carriers, who have been confirmed to be at risk of early and aggressive disease (mainly BRAC2), from around 40 yr of age. The use of multiparametric magnetic resonance imaging in order to avoid unnecessary biopsies is recommended. When a biopsy is performed, a combination of targeted and systematic biopsies must be offered. There is currently no place for the routine use of tissue-based biomarkers. Whilst prostate-specific membrane antigen positron emission tomography computed tomography is the most sensitive staging procedure, the lack of outcome benefit remains a major limitation. Active surveillance (AS) should always be discussed with low-risk patients, as well as with selected intermediate-risk patients with favourable International Society of Urological Pathology (ISUP) 2 lesions. Local therapies are addressed, as well as the AS journey and the management of persistent prostate-specific antigen after surgery. A strong recommendation to consider moderate hypofractionation in intermediate-risk patients is provided. Patients with cN1 PCa should be offered a local treatment combined with long-term hormonal treatment. Conclusions: The evidence in the field of diagnosis, staging, and treatment of localised PCa is evolving rapidly. The 2020 EAU-EANM-ESTRO-ESUR-SIOG guidelines on PCa summarise the most recent findings and advice for their use in clinical practice. These PCa guidelines reflect the multidisciplinary nature of PCa management. Patient summary: Updated prostate cancer guidelines are presented, addressing screening, diagnosis, and local treatment with curative intent. These guidelines rely on the available scientific evidence, and new insights will need to be considered and included on a regular basis. In some cases, the supporting evidence for new treatment options is not yet strong enough to provide a recommendation, which is why continuous updating is important. Patients must be fully informed of all relevant options and, together with their treating physicians, decide on the most optimal management for them. The 2020 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 prostate cancer (PCa) summarise the most recent findings and provide recommendations for clinical practice, addressing screening, diagnosis, and local treatment with curative intent. Key stakeholders in PCa management were involved in their development, including a patient representative. A full version is available at the EAU office and online at http://uroweb.org/guideline/prostate-cancer/. A separate publication will address the management of relapsing-, metastatic-, and castration-resistant PCa.

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. Evidence synthesis: Prostate-specific membrane antigen positron emission tomography computed tomography scanning has developed an increasingly important role in men with biochemical recurrence after local therapy. Early salvage radiotherapy after radical prostatectomy appears as effective as adjuvant radiotherapy and, in a subset of patients, should be combined with androgen deprivation. New treatments have become available for men with metastatic hormone-sensitive prostate cancer (PCa), nonmetastatic CRPC, and metastatic CRPC, along with a role for local radiotherapy in men with low-volume metastatic hormone-sensitive PCa. Also included is information on quality of life outcomes in men with PCa. Conclusions: The knowledge in the field of advanced and metastatic PCa and CRPC is changing rapidly. The 2020 EAU-EANM-ESTRO-ESUR-SIOG guidelines on PCa summarise the most recent findings and advice for use in clinical practice. These PCa guidelines are first endorsed by the EANM and reflect the multidisciplinary nature of PCa management. A full version is available from the EAU office or online (http://uroweb.org/guideline/prostate-cancer/). Patient summary: This article summarises the guidelines for the treatment of relapsing, metastatic, and castration-resistant prostate cancer. These guidelines are evidence based and guide the clinician in the discussion with the patient on the treatment decisions to be taken. These guidelines are updated every year; this summary spans the 2017–2020 period of new evidence. The knowledge in the field of advanced and metastatic prostate cancer (PCa) and castration-resistant prostate cancer is changing rapidly. The 2020 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 PCa summarise the most recent findings and advice for use in clinical practice. These PCa guidelines are first endorsed by the EANM and reflect the multidisciplinary nature of PCa management. A full version is available from the EAU office or online (http://uroweb.org/guideline/prostate-cancer/).

Context: The optimal treatment for men with high-risk localized or locally advanced prostate cancer (PCa) remains unknown. Objective: 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. Evidence acquisition: 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. Evidence synthesis: 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. Conclusions: 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. Patient summary: 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.

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. (C) 2019 Published by Elsevier B.V. on behalf of European Association of Urology.

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. Secondary outcomes included UI at 3–12 mo and ≥12 mo after RP. Evidence acquisition Databases including Medline, EMBASE, and CENTRAL were searched between January 1990 and May 2020. All studies reporting patient- and tumour-related prognostic factors in univariable or multivariable analyses were included. Surgical factors were excluded. Risk of bias (RoB) and confounding assessments were performed using the Quality In Prognosis Studies (QUIPS) tool. Random-effects meta-analyses were performed for all prognostic factor, where possible. Evidence synthesis A total of 119 studies (5 randomised controlled trials, 24 prospective, 88 retrospective, and 2 case-control studies) with 131 379 patients were included. RoB was high for study participation and confounding; moderate to high for statistical analysis, study attrition, and prognostic factor measurement; and low for outcome measurements. Significant prognostic factors for postoperative UI within 3 mo after RP were age (odds ratio [OR] per yearly increase 1.04, 95% confidence interval [CI] 1.03–1.05), membranous urethral length (MUL; OR per 1-mm increase 0.81, 95% CI 0.74–0.88), prostate volume (PV; OR per 1-ml increase 1.005, 95% CI 1.000–1.011), and Charlson comorbidity index (CCI; OR 1.28, 95% CI 1.09–1.50). Conclusions Increasing age, shorter MUL, greater PV, and higher CCI are independent prognostic factors for UI within 3 mo after RP, with all except CCI remaining prognostic at 3–12 mo. Patient summary We reviewed the literature to identify patient and disease factors associated with urinary incontinence after surgery for prostate cancer. We found increasing age, larger prostate volume, shorter length of a section of the urethra (membranous urethra), and lower fitness were associated with worse urinary incontinence for the first 3 mo after surgery, with all except lower fitness remaining predictive at 3–12 mo.

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. All comparative studies for nonmetastatic PCa patients treated with RP published between January 1990 and May 2020 were included. For inclusion, studies had to compare hospital or surgeon volume, defined as caseload per unit time. Main outcomes included oncological (including prostate-specific antigen persistence, positive surgical margin [PSM], biochemical recurrence, local and distant recurrence, and cancer-specific and overall survival) and nononcological (perioperative complications including need for blood transfusion, conversion to open procedure and within 90-d death, and continence and erectile function) outcomes. Risk of bias (RoB) and confounding assessments were undertaken. Both a narrative and a quantitative synthesis were planned if the data allowed. Evidence synthesis Sixty retrospective comparative studies were included. Generally, increasing surgeon and hospital volumes were associated with lower rates of mortality, PSM, adjuvant or salvage therapies, and perioperative complications. Combining group size cut-offs as used in the included studies, the median threshold for hospital volume at which outcomes start to diverge is 86 (interquartile range [IQR] 35–100) cases per year. In addition, above this threshold, the higher the caseload, the better the outcomes, especially for PSM. RoB and confounding were high for most domains. Conclusions Higher surgeon and hospital volumes for RP are associated with lower rates of PSMs, adjuvant or salvage therapies, and perioperative complications. This association becomes apparent from a caseload of >86 (IQR 35–100) per year and may further improve hereafter. Both high- and low-volume centres should measure their outcomes, make them publicly available, and improve their quality of care if needed. Patient summary We reviewed the literature to determine whether the number of prostate cancer operations (radical prostatectomy) performed in a hospital affects the outcomes of surgery. We found that, overall, hospitals with a higher number of operations per year have better outcomes in terms of cancer recurrence and complications during or after hospitalisation. However, it must be noted that surgeons working in hospitals with lower annual operations can still achieve similar or even better outcomes. Therefore, making hospital’s outcome data publicly available should be promoted internationally, so that patients can make an informed decision where they want to be treated.

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. Evidence acquisition Relevant databases were searched for English language articles published between January 1, 1990 and May 8, 2020. Comparative studies for patients with nonmetastatic prostate cancer (PCa) treated with primary RP were included. NS and NNS techniques were compared. The main outcomes were side-specific positive surgical margins (ssPSM) and biochemical recurrence (BCR). Risk of bias (RoB) and confounding assessments were performed. Evidence synthesis Out of 1573 articles identified, 18 studies recruiting a total of 21 654 patients were included. The overall RoB and confounding were high across all domains. The most common selection criteria for NS RP identified were characteristic of low-risk disease, including low core-biopsy involvement. Seven studies evaluated the link with ssPSM and showed an increase in ssPSM after adjustment for side-specific confounders, with the relative risk for NS RP ranging from 1.50 to 1.53. Thirteen papers assessing BCR showed no difference in outcomes with at least 12 mo of follow-up. Lack of data prevented any subgroup analysis for potentially important variables. The definitions of NS were heterogeneous and poorly described in most studies. Conclusions Current data revealed an association between NS surgery and an increase in the risk of ssPSM. This did not translate into a negative impact on BCR, although follow-up was short and many men harbored low-risk PCa. There are significant knowledge gaps in terms of how various patient, disease, and surgical factors affect outcomes. Adequately powered and well-designed prospective trials and cohort studies accounting for these issues with long-term follow-up are recommended. Patient summary Neurovascular bundles (NVBs) are structures containing nerves and blood vessels. The NVBs close to the prostate are responsible for erections. We reviewed the literature to determine if a technique to preserve the NVBs during removal of the prostate causes worse cancer outcomes. We found that NVB preservation was poorly defined but, if applied, was associated with a higher risk of cancer at the margins of the tissue removed, even in patients with low-risk prostate cancer. The long-term importance of this finding for patients is unclear. More data are needed to provide recommendations.

Biochemical recurrence (BCR) after primary treatment of localized prostate cancer does not necessarily lead to clinically apparent progressive disease. To aid in prognostication, the European Association of Urology prostate cancer guidelines panel undertook a systematic review and successfully developed a novel BCR risk stratification system (groups with a low risk or high risk of BCR) based on disease and prostate-specific antigen characteristics. Patient summary: Following treatment to cure prostate cancer, some patients can develop recurrence of disease identified via a prostate-specific antigen blood test (ie, biochemical recurrence, or BCR). However, not every man who experiences BCR develops progressive disease (symptoms or evidence of disease progression on imaging). We conducted a review of the literature and developed a classification system for predicting which patients might progress to optimize treatment decisions. The EAU-EANM-ESTRO-ESUR-SIOG prostate cancer guidelines panel recommends stratifying patients experiencing biochemical recurrence (BCR) after primary treatment for localized prostate cancer into EAU low-risk and high-risk BCR groups. Each patient's risk profile and life expectancy should be considered when discussing the benefits and toxicities of salvage treatments.

Deferred active treatment (DAT) strategies, including active surveillance and active monitoring, are a recognised management option for men with localised low-risk prostate cancer. However, there is uncertainty due to heterogeneity of patient selection criteria, follow-up and monitoring characteristics, reclassification thresholds, and which outcome measures should be prioritised. This protocol describes a study led by the European Association of Urology (EAU) Prostate Cancer Guidelines Panel in conjunction with other guideline organisations and societies to develop consensus statements for all domains of deferred active treatment. The project is divided into 3 sequential phases: (1) Systematic review of studies reporting on DAT in order to summarise and define range of heterogeneity regarding all domains; (2) Two-round Delphi online survey involving a large, international panel of healthcare professionals (HCPs) and patients to initiate consensus; and (3) Consensus group meeting involving representatives from HCP and patient stakeholder groups to finalise the consensus process. The consensus statements are expected to be adopted by clinical practice guidelines in order to standardise and guide practice for clinicians and researchers until better evidence emerges. Patient summary: We describe a project aimed at standardising elements of practice in active surveillance/monitoring for early localised prostate cancer, because currently there is great variation and uncertainty regarding how best to conduct them. This will be achieved through a structured process of agreement (i.e. consensus) amongst a large, international panel of healthcare professionals and patients.