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. A strength rating has been provided for each recommendation according to the EAU Guideline Office methodology. KEY FINDINGS AND LIMITATIONS: Detrusor underactivity (DU) is a urodynamic diagnosis defined as a contraction of reduced strength and/or duration, resulting in prolonged bladder emptying and/or failure to achieve complete bladder emptying within a normal time span. UAB is a terminology that should be reserved for describing symptoms and clinical features related to DU. Invasive urodynamics is the only widely accepted method for diagnosing DU. In patients with persistently elevated postvoid residual (ie, >300 ml), intermittent catheterization is indicated and preferred to indwelling catheters. Alpha-adrenergic blockers are recommended before more invasive techniques, but the level of evidence is low. In men with DU and concomitant benign prostatic obstruction (BPO), benign prostatic surgery should be considered only after appropriate counseling. In men with DU and no BPO, a test phase of sacral neuromodulation may be considered. CONCLUSIONS AND CLINICAL IMPLICATIONS: The current text represents a summary of the new subchapter on UAB. For more detailed information, refer to the full-text version available on the EAU website (https://uroweb.org/guidelines/management-of-non-neurogenic-male-luts). PATIENT SUMMARY: The European Association of Urology guidelines on underactive bladder in non-neurogenic adult men are presented here. Patients must be fully informed of all relevant options and, together with their treating physicians, decide on the most optimal management for them.

Review on the Role of BRCA Mutations in Genomic Screening and Risk Stratification of Prostate Cancer.

(1) Background: Somatic and germline alterations can be commonly found in prostate cancer (PCa) patients. The aim of our present study was to perform a comprehensive review of the current literature in order to examine the impact of BRCA mutations in the context of PCa as well as their significance as genetic biomarkers. (2) Methods: A narrative review of all the available literature was performed. Only "landmark" publications were included. (3) Results: Overall, the number of PCa patients who harbor a BRCA2 mutation range between 1.2% and 3.2%. However, BRCA2 and BRCA1 mutations are responsible for most cases of hereditary PCa, increasing the risk by 3-8.6 times and up to 4 times, respectively. These mutations are correlated with aggressive disease and poor prognosis. Gene testing should be offered to patients with metastatic PCa, those with 2-3 first-degree relatives with PCa, or those aged < 55 and with one close relative with breast (age ≤ 50 years) or invasive ovarian cancer. (4) Conclusions: The individualized assessment of BRCA mutations is an important tool for the risk stratification of PCa patients. It is also a population screening tool which can guide our risk assessment strategies and achieve better results for our patients and their families.

A rare presentation of medullary thyroid cancer metastasis to the prostate in a patient with multiple endocrine neoplasia 2B syndrome treated with laparoscopic radical prostatectomy.

Multiple endocrine neoplasia (MEN) syndromes are rare and potentially malignant hereditary entities. Clinical manifestations of MEN 2B include medullary thyroid cancer, pheochromocytoma, gastrointestinal ganglioneuromatosis, and musculoskeletal and ophthalmologic lesions. Metastases to the prostate from the cancers of other organs are extremely rare. There are only a few cases of metastases to the prostate gland, originating from medullary thyroid cancer, found in literature, especially associated with MEN 2B syndrome. In this case report, we present the extremely rare case of a 28-year-old patient, diagnosed with MEN 2B syndrome, with medullary thyroid cancer metastasis to the prostate. Although a few reports of medullary thyroid cancer metastasis into the prostate gland can be found in the literature, to our knowledge, this is the first case of a laparoscopic radical prostatectomy procedure performed as a metastasectomy to treat the prostatic metastasis. Laparoscopic radical prostatectomy, performed as a metastasectomy, for the treatment of metastatic cancer, is an extremely rare surgical indication with distinctive requirements and difficulties. The extraperitoneal access enables the realization of the laparoscopic radical prostatectomy procedure even in the cases of patients with a history of multiple intra-abdominal operations.

Summary Paper on the 2023 European Association of Urology Guidelines on the Management of Non-neurogenic Male Lower Urinary Tract Symptoms.

CONTEXT: Lower urinary tract symptoms (LUTS) are common, often bothersome, and have multifactorial aetiology. OBJECTIVE: To present a summary of the 2023 version of the European Association of Urology guidelines on the management of male LUTS. EVIDENCE ACQUISITION: A structured literature search from 1966 to 2021 selected the articles with the highest certainty evidence. The Delphi technique consensus approach was used to develop the recommendations. EVIDENCE SYNTHESIS: The assessment of men with LUTS should be practical. A careful medical history and physical examination are essential. Validated symptom scores, urine test, uroflowmetry, and postvoid urine residual, as well as frequency-volume charts for patients with nocturia or predominately storage symptoms should be used. Prostate-specific antigen should be ordered if a diagnosis of prostate cancer changes the treatment plan. Urodynamics should be performed for selected patients. Men with mild symptoms are candidates for watchful waiting. Behavioural modification should be offered to men with LUTS prior to, or concurrent with, treatment. The choice of medical treatment depends on the assessment findings, predominant type of symptoms, ability of the treatment to change the findings, and the expectations to be met in terms of the speed of onset, efficacy, side effects, and disease progression. Surgery is reserved for men with absolute indications, and for patients who fail or prefer not to receive medical therapy. Surgical management has been divided into five sections: resection, enucleation, vaporisation, and alternative ablative and nonablative techniques. The choice of surgical technique depends on patient's characteristics, expectations, and preferences; surgeon's expertise; and availability of modalities. CONCLUSIONS: The guidelines provide an evidence-based approach for the management of male LUTS. PATIENT SUMMARY: A clinical assessment should identify the cause(s) of symptoms and define the clinical profile and patient's expectations. The treatment should aim to ameliorate symptoms and reduce the risk of complications.

Laparoscopic Radical Prostatectomy Performed in a Patient With Zinner's Syndrome: The First Case Described in the Literature.

Zinner's syndrome is a rare congenital disorder presenting with unilateral renal agenesis or dysgenesis, ipsilateral seminal vesicle cysts, and ejaculatory duct obstruction. Treatment of this syndrome can be conservative or surgical. In this case report, we describe the case of a 72-year-old patient who was diagnosed with Zinner's syndrome and underwent laparoscopic radical prostatectomy for prostate cancer treatment. The peculiarity of our case was that the patient's ureter emptied ectopically into the left seminal vesicle, which was notably enlarged and multicystic in appearance. Although many minimally invasive procedures have been reported for treating symptomatic Zinner's syndrome, to our knowledge, this is the first reported case of prostate cancer in a patient with Zinner's syndrome who was treated with laparoscopic radical prostatectomy. Laparoscopic radical prostatectomy can be safely and efficiently performed in patients with Zinner's syndrome and synchronous prostate cancer by urological surgeons with extensive experience in laparoscopy in high-volume centers.

Rezum water vapor therapy for the treatment of patients with urinary retention and permanent catheter dependence secondary to benign prostate hyperplasia: a systematic review of the literature.

PURPOSE: Recurrent urinary retention due to benign prostate hyperplasia (BPH), requiring permanent catheterization, represents one of the most challenging issues geriatric patients can face. Rezum, as a minimal invasive treatment for BPH, takes the advantage of sterile water vapor injections directly into the prostate. The purpose of this Systematic Review is to report the safety and the efficacy of Rezum regarding urinary retention relief and permanent catheter withdrawal. METHODS: PubMed, Scopus and Cochrane databases were meticulously screened using the keywords "Rezum", "retention" and "permanent catheter". Only human studies and articles in English were included. Rezum should be the only intervention employed in patients. Patients of included studies should not have been submitted to any prior interventions, such as transurethral prostatectomy (TURP) for the relief of their symptoms. Patients' baseline characteristics along with intraoperative and postoperative parameters were collected and analysed. Catheter relief was the primary outcome. RESULTS: Five studies fulfilled all the criteria and were included in the final qualitative synthesis. Four studies were retrospective and one was prospective. All studies were non-comparative. The success rate ranged from 70.3 to 100%, while no grade ≥ III Clavien-Dindo complications were reported in any of the studies. CONCLUSION: Rezum Water Vapor Therapy Treatment seems to be a feasible, safe and efficient minimally-invasive procedure for catheterized patients with urinary retention secondary to BPH, especially for frail ones with comorbidities who cannot undergo general anesthesia.

European Association of Urology Guidelines on Male Urinary Incontinence.

CONTEXT: Urinary incontinence (UI) is a common condition in elderly men causing a severe worsening of quality of life, and a significant cost for both patients and health systems. OBJECTIVE: To report a practical, evidence-based, guideline on definitions, pathophysiology, diagnostic workup, and treatment options for men with different forms of UI. EVIDENCE ACQUISITION: A comprehensive literature search, limited to studies representing high levels of evidence and published in the English language, was performed. Databases searched included Medline, EMBASE, and the Cochrane Libraries. A level of evidence and a grade of recommendation were assigned. EVIDENCE SYNTHESIS: UI can be classified into stress urinary incontinence (SUI), urge urinary incontinence (UUI), and mixed urinary incontinence. A detailed description of the pathophysiology and diagnostic workup has been reported. Simple clinical interventions, behavioural and physical modifications, and pharmacological treatments comprise the initial management for all kinds of UI. Surgery for SUI includes bulking agents, male sling, and compression devices. Surgery for UUI includes bladder wall injection of botulinum toxin A, sacral nerve stimulation, and cystoplasty/urinary diversion. CONCLUSIONS: This 2022 European Association of Urology guideline summary provides updated information on definition, pathophysiology, diagnosis, and treatment of male UI. PATIENT SUMMARY: Male urinary incontinence comprises a broad subject area, much of which has been covered for the first time in the literature in a single manuscript. The European Association of Urology Non-neurogenic Male Lower Urinary Tract Symptoms Guideline Panel has released this new guidance, with the aim to provide updated information for urologists to be able to follow diagnostic and therapeutic indications for optimising patient care.

Nondetectable Prostate Carcinoma (pT0) after Radical Prostatectomy: A Narrative Review.

(1) Background: Following radical prostatectomy (RP), the absence of a demonstrable tumor on the specimen of a previously histologically proven malignancy is known as the pT0 stage. The aim of our present study is to perform a narrative review of current literature in order to determine the frequency and oncological outcomes in patients with pT0 disease. (2) Methods: A narrative review of all available literature was performed. (3) Results: The incidence of pT0 ranges between 0.07% and 1.3%. Predictors of the pT0 stage are only a single biopsy core with low-grade cancer, a cancer length not exceeding 2 mm and a high prostate volume. Biochemical recurrence ranges between 0 and 11%. (4) Conclusions: The absence of malignancy in the RP specimen despite a previous positive biopsy is a rare and unpredictable finding. Although the prognosis is considered to be excellent in most of the cases, a continued close follow-up is warranted.

Learning curves in laparoscopic and robot-assisted prostate surgery: a systematic search and review.

PURPOSE: To perform a systematic search and review of the available literature on the learning curves (LCs) in laparoscopic and robot-assisted prostate surgery. METHODS: Medline was systematically searched from 1946 to January 2021 to detect all studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement, reporting on the LC in laparoscopic radical prostatectomy (LRP), laparoscopic simple prostatectomy (LSP), robot-assisted radical prostatectomy (RARP) and robot-assisted simple prostatectomy (RSP). RESULTS: In total, 47 studies were included for qualitative synthesis evaluating a single technique (LRP, RARP, LSP, RSP; 45 studies) or two techniques (LRP and RARP; 2 studies). All studies evaluated outcomes on real patients. RARP was the most widely investigated technique (30 studies), followed by LRP (17 studies), LSP (1 study), and RSP (1 study). In LRP, the reported LC based on operative time; estimated blood loss; length of hospital stay; positive surgical margin; biochemical recurrence; overall complication rate; and urinary continence rate ranged 40-250, 80-250, 58-200, 50-350, 110-350, 55-250, 70-350 cases, respectively. In RARP, the corresponding ranges were 16-300, 20-300, 25-200, 50-400, 40-100, 20-250, 30-200, while LC for potency rates was 80-90 cases. CONCLUSIONS: The definition of LC for laparoscopic and robot-assisted prostate surgery is not well defined with various metrics used among studies. Nevertheless, LCs appear to be steep and continuous. Implementation of training programs/standardization of the techniques is necessary to improve outcomes.

Management of Urinary Retention in Patients with Benign Prostatic Obstruction: A Systematic Review and Meta-analysis.

CONTEXT: Practice patterns for the management of urinary retention (UR) secondary to benign prostatic obstruction (BPO; UR/BPO) vary widely and remain unstandardized. OBJECTIVE: To review the evidence for managing patients with UR/BPO with pharmacological and nonpharmacological treatments included in the European Association of Urology guidelines on non-neurogenic male lower urinary tract symptoms. EVIDENCE ACQUISITION: Search was conducted up to April 22, 2018, using CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform. This systematic review included randomized controlled trials (RCTs) and prospective comparative studies. Methods as detailed in the Cochrane handbook were followed. Certainty of evidence (CoE) was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. EVIDENCE SYNTHESIS: Literature search identified 2074 citations. Twenty-one studies were included (qualitative synthesis). The evidence for managing patients with UR/BPO with pharmacological or nonpharmacological treatments is limited. CoE for most outcomes was low/very low. Only α1-blockers (alfuzosin and tamsulosin) have been evaluated in more than one RCT. Pooled results indicated that α1-blockers provided significantly higher rates of successful trial without catheter compared with placebo [alfuzosin: 322/540 (60%) vs 156/400 (39%) (odds ratio {OR} 2.28, 95% confidence interval {CI} 1.55 to 3.36; participants=940; studies=7; I2=41%; low CoE); tamsulosin: 75/158 (47%) vs 40/139 (29%) (OR 2.40, 95% CI 1.29 to 4.45; participants=297; studies=3; I2=30%; low CoE)] with rare adverse events. Similar rates were achieved with tamsulosin or alfuzosin [51/87 (59%) vs 45/84 (54%) (OR 1.28, 95% CI 0.68 to 2.41; participants=171; studies=2; I2=0%; very low CoE)]. Nonpharmacological treatments have been evaluated in RCTs/prospective comparative studies only sporadically. CONCLUSIONS: There is some evidence that usage of α1-blockers (alfuzosin and tamsulosin) may improve resolution of UR/BPO. As most nonpharmacological treatments have not been evaluated in patients with UR/BPO, the evidence is inconclusive about their benefits and harms. PATIENT SUMMARY: There is some evidence that alfuzosin and tamsulosin may increase the rates of successful trial without catheter, but little or no evidence on various nonpharmacological treatment options for managing patients with urinary retention secondary to benign prostatic obstruction.

Pattern of somatostatin receptors expression in normal and bladder cancer tissue samples.

BACKGROUND/AIM: Known risks factors for bladder cancer progression and recurrence are limited regarding their prognostic ability. Therefore identification of molecular determinants of disease progression could provide with more specific prognostic information and could be translated into new approaches for biomarker development. In the present study we evaluated, the expression patterns of somatostatin receptors 1-5 (SSTRs) in normal and tumor bladder tissues. MATERIALS AND METHODS: The expression of SSTR1-5 was characterized in 45 normal and bladder cancer tissue samples using reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: SSTR1 was expressed in 24 samples, SSTR2 in 15, SSTR3 in 23, SSTR4 in 16 and SSTR5 in all but one sample. Bladder cancer tissue samples expressed lower levels of SSTR3. Co-expression of SSTRs was associated with superficial disease. CONCLUSION: Our results demonstrate, for the first time, that there is expression of SSTR in normal and bladder cancer urothelium. Further studies are required to evaluate the prognostic and therapeutic significance of these findings.

Anatomically versus biologically unifocal prostate cancer: a pathological evaluation in the context of focal therapy.

OBJECTIVES: Since tumor focality in prostate cancer continues to be considered a major limitation for focal prostate therapy, in this study we attempted to compare the pathological features and the proportion of patients with anatomically unifocal versus biologically unifocal tumors (i.e. multifocal prostate cancer in which the secondary nonindex elements are small, low grade and clinically insignificant) who were suitable for focal therapy. METHODS: Ninety-five consecutive whole mount laparoscopic radical prostatectomy samples underwent pathological assessment (from January 2007 to November 2009). Tumor focality, laterality, Gleason score and volume of individual foci, total tumor volume, pathological stage and surgical margin status were assessed. The index lesion was defined as the largest by volume. Patients suitable for focal ablation were defined as having tumors that were unifocal, organ confined, with a Gleason score (GS) up to 7 prostate cancer, or multifocal, organ confined, GS up to 7 prostate cancer, with one large index lesion and the remaining foci demonstrating features of clinically insignificant disease (total tumor volume of all secondary foci ≤0.5 cm(3) with GS ≤ 6). RESULTS: Patients with biologically unifocal cancer had significantly lower total tumor volume (3.26 versus 7.28 cm(3); p < 0.001), index lesion volume (2.9 versus 7.16 cm(3); p < 0.001), rates of seminal vesicle invasion (4% versus 34%; p < 0.001), rates of positive surgical margins (22.4% versus 52.1%; p < 0.001) and rates of 4+3 GS tumors (10.2% versus 29.1%; p = 0.018). The proportion of patients suitable for focal therapy was higher in the biologically unifocal versus anatomically unifocal cancer group, although without reaching statistical significance (65.3% versus 45.8%; p = 0.11). CONCLUSIONS: Patients with biologically unifocal tumors have better pathological outcome than those with anatomically unifocal disease. At present the assumption that multifocality should a priori exclude patients from any organ-preserving prostate cancer treatment is only theoretical and needs to be validated by future clinical trials since there are a large proportion of patients with multifocal disease apparently suitable for focal prostate therapy.

Trends in pathologic outcomes after introduction of active surveillance in the UK: implication for focal therapy.

BACKGROUND: We aimed to evaluate the trends in pathologic outcomes of clinically localized prostate cancer treated with radical prostatectomy prior to and after national guidelines placing active surveillance as the primary management in men with low-risk prostate cancer. Further, we examined whether there was a coincident change in the proportion of men potentially suitable for focal therapy. METHODS: All cancer foci in 195 whole mount radical prostatectomy samples during two periods (Period 1: 07/2001-10/2003, n = 100 and Period 2: 01/2007-11/2009, n = 95) were examined. Individual tumor volumes, Gleason grade, and extracapsular extension/positive surgical margins were evaluated. The index lesion was defined as the largest by volume. RESULTS: There was a statistically significant increase in the proportion of Gleason score ≥7 tumors (31-69%; P < 0.001) and pathologically non-organ confined disease (21-37%; P = 0.008), between period 1 and 2, respectively. The proportion of patients with unifocal prostate cancer potentially suitable for focal ablation was stable (14-13.7%; P = 0.9). Although there was a decrease in the proportion of patients potentially suitable for index lesion ablation (51-43%; P = 0.4) and unilateral prostate cancer potentially suitable for hemi-ablation (11-6.3%; P = 0.3), these differences were not statistically significant. CONCLUSION: The increasing use of active surveillance in the UK may be responsible for a trend towards higher grade and stage prostate cancer in whole mount specimens. Despite this, there remain a significant proportion of men who currently undergo radical surgery who may be suitable for focal therapy, if that included index lesion ablation.

Margin status after laparoscopic radical prostatectomy and the index lesion: implications for preoperative evaluation of tumor focality in prostate cancer.

PURPOSE: The objective of this study was to evaluate the impact of tumor focality on positive surgical margins (PSM) after laparoscopic radical prostatectomy. PATIENTS AND METHODS: Ninety-five consecutive whole-mount laparoscopic radical prostatectomy samples (January 2007 to November 2009) were evaluated for tumor focality, laterality, Gleason score, and volume of individual foci, total tumor volume, pathologic stage, and surgical margin status. RESULTS: Thirty-nine percent, 36%, and 25% were in low, intermediate, and high D'Amico risk categories. Thirty-three percent (31/95) had PSM. Overall, 269 tumor foci were identified. The incidence of PSM within lesions ≤ 0.5 cc and ≤ 0.2 cc was 1.2% (2/160) and 0% (0/132), respectively. Among the 71 multifocal cases, 19 (27%) exhibited PSM. In 13 of these, the index lesion appeared at the inked surface (mean volume 5.4 cc, range 0.63-26.9 cc) compared with 6 in which both index and satellite foci appeared at the inked margins. Mean volume of these satellite foci was 1.06 cc (range 0.22-2 cc); three had Gleason score 6 and three had Gleason score 7 (3+4). CONCLUSIONS: PSM is usually attributed to the index lesion and lesions larger than commonly used thresholds for clinically significant lesion volumes. Because such lesions might be detected by multiparametric magnetic resonance imaging (MRI) or template mapping biopsies, the information from these staging modalities could be used intraoperatively to reduce PSM.

Focal therapy for prostate cancer: opportunities and uncertainties.

Prostate cancer is the most common cancer and the second most common cause of cancer-related death in men. Screening with prostate specific antigen (PSA) has led to a clinical and pathological stage migration such that currently most men diagnosed with prostate cancer have clinically localized disease potentially offering opportunity for curative intervention. On the other hand, the benefit of radical therapy in terms of reducing overall mortality in PSA-screened populations has been controversial with concerns being raised about over-diagnosis and over-treatment. Treatment of prostate cancer is associated with risk and complications that negatively affect the quality of life of men with localized disease. Recently, a new treatment paradigm has been proposed which is called focal therapy, defined as an individualized treatment by which only known disease is targeted and ablated while preserving normal tissue. This review will attempt to describe the opportunities and uncertainties behind this proposed paradigm shift.

Expression of ERß and its co-regulators p300 and NCoR in human transitional cell bladder cancer.

OBJECTIVE: Several data support a possible role of estrogens in bladder carcinogenesis, mediated mainly through estrogen receptor-ß (ERß). We study the expression of ERß and its co-regulators p300 and nuclear co-repressor (NCoR) in patients with bladder cancer. PATIENTS AND METHODS: One hundred and eleven consecutive patients (74 males and 37 females), aged 23-90 years (mean 70 ± 10) diagnosed with transitional cell bladder cancer were included in this study. The control group consisted of 29 patients that underwent transurethral prostatectomy and consented to simultaneous bladder biopsies. Immunohistochemical studies took place on formalin-fixed, paraffin-embedded sections from the TUR (transurethral resection) specimens. We studied the expression of ERß, p300 and NCoR.χ(2) test was used to evaluate the relationship between the histological grade and ERß expression, grade and co-regulators expression and grade and gender. Spearman rank correlation coefficient (r) was used in order to estimate the direction and strength of correlations between histological grade and ERß-p300-NCoR expressions. The Cochran-Armitage test for trend was applied in order to examine possible trends across the ordered levels of histological grade. RESULTS: ERß was more frequently expressed in the nucleus of normal bladder epithelium compared to malignant bladder epithelium with statistical significant association (r = -0.25, p = 0.003). The p300 was expressed only in the nucleus of bladder cancer cells and a positive correlation between molecular expression and cancer progression was demonstrated (r = 0.55, p < 0.001). NCoR immunostaining was demonstrated in the nuclei of bladder cells. Nuclear staining was significantly higher in normal tissue than in cancer cells (r = -0.33, p < 0.001), with negative correlation. Furthermore, its expression in grade I tumors was significantly higher than in grade II (r = -0.46, p < 0.001) and grade III tumors (r = -0.51, p < 0.001). Thus, like ERß, NCoR expression in bladder epithelium decreased during cancer progression and loss of cell differentiation. There was no correlation between the levels of expression of the three proteins in normal bladder epithelium, but there was an inverse correlation between the nuclear expression of ERß and p300 in carcinomas (r = -3.88, p = 0.042). Statistical significant association was established when correlating ERß expression with NCoR expression (r = 0.273, p = 0.005), while co-regulators' nuclear expression did not correlate with each other (p > 0.05). CONCLUSIONS: In bladder carcinogenesis, we demonstrated inhibition in the expression of ERß and its co-repressor NCoR as well as increased expression of the co-activator p300.