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Objective: To access the feasibility of palliative cystoprostatectomy/pelvic exenteration in patients with bladder/rectal invasion due to prostate cancer (PC). Patients and methods: Twenty-five men with cT4 PC were retrospectively identified in the institutional databases of six tertiary referral centers in the last decade. Local invasion was documented by CT or MRI scans and was confirmed by urethrocystoscopy. Oncological therapies, local symptoms, previous local treatments, time from diagnosis to intervention and type of surgical procedure were recorded. Patients were divided into groups: ADT group (12 pts) and 13 pts without any history of previous local/systemic treatments for PCa (nonADT groups). Perioperative complications were classified using the Clavien–Dindo system. Overall survival (OS) was defined as the time from surgery to death from any cause. A Cox regression analysis, stratified for ISUP score and previous hormonal treatment (ADT) was also performed for survival analysis. Results: Ileal conduit was the main urinary diversion in both cohorts. For the entire cohort, complication rate was 44%. No significant differences regarding perioperative complications and complication severity between both subgroups were observed (p = 0.2). Median follow-up was 15months (range 3–41) for the entire cohort with a median survival of 15months (95% CI 10.1–19.9). In Cox regression analysis stratified for ISUP score, no statistically significant differences in OS in patients with and without previous ADT before cystectomy or exenteration were observed (HR 3.26, 95% CI 0.62–17.23, p = 0.164). Conclusion: Palliative cystoprostatectomy and pelvic exenteration represent viable treatment options associated with acceptable morbidity and good short-term survival outcome.

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.

Background: Besides second-generation hormone therapy (sHT), upfront docetaxel along with androgen deprivation therapy is the current standard of care for metastasized hormone-sensitive prostate cancer (mHSPC). Evidence on second-line therapy upon progression on chemohormonal treatment outside clinical trials is scarce. Objective: To comparatively assess the efficacy of subsequent therapy after upfront docetaxel in mHSPC in a real-world setting. Design, setting, and participants: This is a retrospective multicenter analysis. Males with mHSPC on androgen-deprivation therapy progressed to castration-resistant prostate cancer (CRPC) after upfront docetaxel. Outcome measurements and statistical analysis: Overall survival (OS), progression-free survival 2 (PFS2), and time to progression 2 (TTP2) were assessed. Chi-square test and Mann-Whitney U test were used for univariate comparison between the sHT and non-sHT (other therapies) cohorts. Median time to event was tested by Kaplan-Meier method and log-rank test. Univariate and multivariate analysis regression was performed with the Cox proportional-hazard model. Results and limitations: Sixty-five patients were included in the final analysis. Median TTP2 was 20 mo, median PFS2 was 29 mo, and median OS was not reached; sHT was an independent predictor of favorable PFS2 as compared with non-sHT. Time to CRPC was also confirmed to be the strongest predictor for novel endpoints PFS2 and TTP2. Time to CRPC >18 mo conferred advantage to sHT over non-sHT in relation to PFS2 and OS. Second-line therapies were well tolerated. The analysis is prone to inherent flaws and biases due to its retrospective nature. Conclusions: In real-world patients progressing after upfront docetaxel, sHT is independently associated with favorable PFS2 favoring drug class switch. Longer time to CRPC predicts strongly for superior PFS2 and TTP2. Further prospective research is warranted in order to guide treatment sequencing and improve outcomes and quality of life of males with metastasized prostate cancer. Patient summary: We analyzed the efficacy of second-line therapy after docetaxel in hormone-dependent metastatic prostate cancer. Novel hormone therapy appears to be a preferable option for deferring progression optimally. Larger patient databases are eagerly awaited. In real-world patients progressing after upfront docetaxel, second-generation hormone therapy is independently associated with superior progression-free survival 2 (PFS2) favoring drug class switch. Longer time to castration-resistant prostate cancer predicts strongly for superior PFS2 and time to progression 2.

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 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.

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.

Objective: Radical prostatectomy (RP) is a frequent treatment for men suffering from localized prostate cancer (PCa). Whilst offering a high chance for cure, it does not come without a significant impact on health-related quality of life. Herein we review the common adverse effects RP may have over the course of time. Methods: A collaborative narrative review was performed with the identification of the principal studies on the topic. The search was executed by a relevant term search on PubMed from 2010 to February 2021. Results: Rates of major complications in patients undergoing RP are generally low. The main adverse effects are erectile dysfunction varying from 11 to 87% and urinary incontinence varying from 0 to 87% with a peak in functional decline shortly after surgery, and dependent on definitions. Different less frequent side effects also need to be taken into account. The highest rate of recovery is seen within the first year after RP, but even long-term improvements are possible. Nevertheless, for some men these adverse effects are long lasting and different, less frequent side effects also need to be taken into account. Despite many technical advances over the last two decades no surgical approach can be clearly favored when looking at long-term outcome, as surgical volume and experience as well as individual patient characteristics are still the most influential variables. Conclusions: The frequency of erectile function and urinary continence side effects after RP, and the trajectory of recovery, need to be taken into account when counseling patients about their treatment options for prostate cancer. OA Förderung 2021

Context The assessment of “soft” endpoints such as health-related quality of life (HRQOL) is increasingly relevant when evaluating the optimal treatment sequence of novel therapeutic options in patients with advanced prostate cancer (PCa). Objective To systematically review contemporary data regarding HRQOL outcomes in patients with advanced PCa. Evidence acquisition A systematic review of the literature published between January 2011 and March 2019 was performed using the PubMed/Medline Database. In total, 873 articles were screened, and 14 articles including 12 661 patients were selected for synthesis and included in the current analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) and European Association of Urology recommendations. Evidence synthesis Regarding HRQOL assessment, the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire was used in 11 of 14 studies, the European Quality of Life 5-Dimensions (EQ-5D) questionnaire in six of 14 studies, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) in two of 14, and its prostate-specific amendment QLQ-PR25 was used in one of 14 studies. Three studies included patients with metastatic castration-sensitive prostate PCa, and found beneficial HRQOL effects for abiraterone acetate and docetaxel compared with standard androgen deprivation therapy. Two studies included patients with nonmetastatic castration-resistant PCa, and positive HRQOL effects for enzalutamide and apalutamide were observed. Nine studies focused on patients with metastatic castration-resistant PCa. Hereby, beneficial HRQOL outcomes were described for enzalutamide, abiraterone acetate, and radium-223. Evidence synthesis was mostly based on studies with a low risk of bias based on standardized risk of bias assessment. Limitations include hampered comparability between different validated questionnaires, lack of baseline values, and unclear impact of supportive care on HRQOL outcomes. Conclusions There is strong evidence from several phase III trials supporting a beneficial effect of current systemic treatment options on HRQOL outcomes in patients with advanced PCa compared with standard androgen deprivation therapy. Patient summary In this systematic review, we provide an overview of contemporary data from large clinical trials on the effect of current treatment strategies on patients’ health-related quality of life (HRQOL). We summarize the assessment tools that have been used to measure HRQOL and show that there are robust data for positive HRQOL effects of numerous agents in different clinical stages of advanced prostate cancer.

Background: Although an increasing number of prostate cancer (PCa) patients received holmium laser enucleation of the prostate (HoLEP) previously for benign prostatic obstruction (BPO), there is still no evidence regarding the outcomes of radical prostatectomy (RP) in this setting. Objective: To assess functional and oncological results of RP in PCa patients who received HoLEP for BPO previously in a contemporary multi-institutional cohort. Design, setting, and participants: A total of 95 patients who underwent RP between 2011 and 2019 and had a history of HoLEP were identified in two institutions. Functional as well as oncological follow-up was prospectively assessed and retrospectively analyzed. Intervention: RP following HoLEP compared with RP without previous transurethral surgery. Outcome measurements and statistical analysis: Patients with complete follow-up data were matched with individuals with no history of BPO surgery using propensity score matching. Complications were assessed using the Clavien-Dindo scale. Results and limitations: The median follow-up was 50.5 mo. We found no significant impact of previous HoLEP on positive surgical margin rate (14.0% [HoLEP] vs 18.8% [no HoLEP], p = 0.06) and biochemical recurrence-free survival (hazard ratio 0.74, 95% confidence interval [CI] 0.32–1.70, p = 0.4). Patients with a history of HoLEP had increased 1-yr urinary incontinence rates after RP. After adjusting for confounders, no significant impact of previous HoLEP was found (odds ratio [OR] 0.87, 95% CI 0.74–1.01; p = 0.07). Previous HoLEP did not hamper 1-yr erectile function recovery (OR 1.22, 95% CI 1.05–1.43; p = 0.01). Limitations include retrospective design and small sample size. Conclusions: RP after previous HoLEP is surgically feasible, with low complication rates and no negative impact on biochemical recurrence–free survival. However, in a multivariable analysis, we observed significantly worse 1-yr continence rates in patients after previous HoLEP. Patient summary: In the current study, we assessed the oncological and functional outcomes of radical prostatectomy in patients who underwent holmium laser enucleation of the prostate (HoLEP) previously due to prostatic bladder outlet obstruction. A history of HoLEP did not hamper oncological results, 1-yr continence, and erectile function recovery. We provide data from a propensity score–matched population of patients who underwent radical prostatectomy with or without previous holmium laser enucleation of the prostate (HoLEP). In multivariable analyses, no differences were found in biochemical recurrence–free survival, positive surgical margin rates, and 1-yr continence recovery. Patients with previous HoLEP had similar rates of bilateral nerve sparing and increased 1-yrerectile function recovery compared with those without previous HoLEP.

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.

Background Docetaxel (D) or secondary hormonal therapy (SHT) each combined with androgen deprivation therapy (ADT) represent possible treatment options in males with metastasized hormone‐sensitive prostate cancer (mHSPC). Real‐world data comparing different protocols are lacking yet. Thus, our objective was to compare the efficacy and safety of abiraterone acetate (AA)+ADT versus D+ADT in mHSPC. Methods In a retrospective multicenter analysis including males with mHSPC treated with either of the aforementioned protocols, overall survival (OS), progression‐free survival 1 (PFS1), and progression‐free survival 2 (PFS2) were assessed for both cohorts. Median time to event was tested by Kaplan–Meier method and log‐rank test. The Cox‐proportional hazards model was used for univariate and multivariate regression analyses. Results Overall, 196 patients were included. The AA+ADT cohort had a longer PFS1 in the log‐rank testing (23 vs. 13 mos., p, Abiratreone acetate outperforms docetaxel in terms of PFS and PFS2, while the impact on OS as well as the rate of side effects is similar between both groups in real‐life utilization. Prospective randomized trials of available agents in mHSPC are required to generate high‐level evidence to facilitate sensible drug selection

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 Optimal management of prostate cancer (PCa) patients with lymph node invasion at radical prostatectomy and pelvic lymph node dissection still remains unclear. Objective To assess the effectiveness of postoperative treatment strategies for pathologically node-positive PCa patients. The secondary aim was to identify the most relevant prognostic factors to guide the management of pN1 patients. Evidence acquisition A systematic review was performed in January 2020 using Medline, Embase, and other databases. A total of 5063 articles were screened, and 26 studies including 12 537 men were selected for data synthesis and included in the current review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) recommendations. Evidence synthesis Ten-year biochemical recurrence (BCR)-free, clinical recurrence–free, cancer-specific (CSS), and overall (OS) survival rates ranged from 28% to 56%, 70% to 92%, 72% to 98%, and 60% to 87.6%, respectively. A total of seven, five, and six studies assessed the oncological outcomes of observation, adjuvant radiotherapy (aRT), or adjuvant androgen deprivation therapy (ADT), respectively. Initial observation followed by salvage therapies at the time of recurrence represents a safe option in selected patients with a low disease burden. The use of aRT with or without ADT might improve survival in men with locally advanced disease and a higher number of positive nodes. Risk stratification according to pathological Gleason score, number of positive nodes, pathological stage, and surgical margins status is the key to risk stratification and selection of the optimal postoperative therapy. Limitations of this systematic review are the retrospective design of the studies included and the lack of data on adverse events. Conclusions While the majority of men with pN1 disease would experience BCR after surgery, long-term disease-free survival has been reported in selected patients. Management options to improve oncological outcomes include observation versus adjuvant therapies such as aRT and/or ADT. Disease characteristics should be used to select the optimal postoperative management for pN1 PCa patients. Patient summary Finding node-positive prostate cancer after a radical prostatectomy often leads to high postoperative prostate-specific antigen levels and is overall a poor prognostic factor. However, this does not necessarily translate into poor survival for all men. Management can be tailored to the severity of disease and options include observation, androgen deprivation therapy, and/or radiotherapy.

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.

Prostate cancer (PCa) remains the most common cancer in men. The proportion of all PCa attributable to high-risk hereditary factors has been estimated to 5-15%. Recent landmark discoveries in PCa genetics led to the identification of germline mutations/alterations (eg. BRCA1, BRCA2, ATM or HOXB13), single nucleotide polymorphisms or copy number variations associated with PCa incidence and progression. However, offering germline testing to men with an assumed hereditary component is currently controversial. In the present review article, we provide an overview about the epidemiology and the genetic basis of PCa predisposition and critically discuss the significance and consequence in the clinical routine. In addition, we give an overview about genetic tests and report latest findings from ongoing clinical studies. Lastly, we discuss the impact of genetic testing in personalized therapy in advanced stages of the disease.