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Introduction: Botulinum neurotoxin A (BoNT-A) is a treatment option for neurogenic lower urinary tract dysfunctions (NLUTD) and idiopathic overactive bladder (OAB) in adults. Recently, its use has gained popularity in paediatric urology. Transitional urology deals with adolescents affected by congenital urological issues, who mature into adulthood. The aim of this systematic review was to update the current knowledge on the use of BoNT-A in children and adolescents., Methods: A comprehensive search in PubMed, Scopus, and Web of Science databases was performed from articles published up to September 2024. Both prospective and retrospective single-cohort or comparative studies evaluating outcomes of interest were included. These consisted of the amelioration of urinary incontinence (UI), continence rates, improvement of urodynamic parameters (maximum detrusor pressure during voiding, maximum bladder capacity, and bladder compliance), and type and prevalence of adverse/side effects. Qualitative and quantitative data syntheses were provided. Moderators and meta-regression analyses were carried out as well., Results: Forty-one full-text manuscripts were selected of which 26 focused on children with NLUTD, 13 on idiopathic OAB, and two on both conditions. Overall, 1521 patients were included of whom 715 were male, 646 female, and 160 of unknown sex. Mean age varied between 5.6 and 15.6 years. No studies specifically focused on transitional urology, despite patients up to at least 17 years of age being included. Several differences existed in design, type, dose, way of administration, outcomes measured and follow-up time; however, all studies independently showed an improvement of UI and urodynamic parameters with no major side/adverse events. Pooled analysis showed a mean rate of improvement in UI scores/episodes of 75.87% within a period of 3-6 months following BoNT-A treatment. Meta-regression analyses demonstrated a significant correlation between dryness rate and both patients' age (negative) and bladder compliance (positive)., Conclusions: Several uncontrolled or comparative studies provided significative evidence of the clinical benefit and safety of BoNT-A administration in children in terms of UI relief and improvement of urodynamic parameters, with neurogenic aetiologies being the most investigated conditions. A reduced bladder compliance was identified as one of the potential predictors of poor response to BoNT-A. Moreover, the earlier the treatment was started the higher the success rate that was reached in terms of dryness/urinary continence achievement.

Objective: To assess whether tumor location at diagnostic TURBT is predictive of ipsilateral nodal involvement in patients who underwent radical cystectomy (RC) with lymph-nodes dissection for bladder cancer (BCa)., Materials and Methods: All patients who underwent RC for BCa at a single institution between 2014-2023 were assessed. Tumor location at TURBT was defined as right-sided, median-line, left-sided, and diffused. Distribution in the percentage of ipsilateral positive lymph-nodes and number of ipsilateral positive lymph-nodes between tumor locations were assessed with Kruskal-Wallis tests. Linear regressions were fitted to assess whether left or right location, compared to the remaining locations grouped, was associated to the percentage and number of positive ipsilateral lymph-nodes., Results: 239 patients were included. The number of ipsilateral positive lymph nodes was superior in right-sided tumors when compared to the rest of the bladder (0, I.Q.R. 0-1 vs. 0, I.Q.R. 0-0, P = 0.047), as well as the percentage of ipsilateral positive lymph-nodes (0, I.Q.R. 0-14.3 vs. 0, I.Q.R. 0-3.7, P = 0.042). The number of ipsilateral positive lymph-nodes in left-sided tumors was superior when compared to the rest of the bladder (0, I.Q.R. 0-1 vs. 0, I.Q.R. 0-0, P = 0.02), as well as the percentage (0, I.Q.R. 0-13.7 vs. 0, I.Q.R. 0-0, P = 0.036). At linear regression analyses, right- and left-sided tumors were associated with an increased percentage of ipsilateral positive lymph-nodes (P = 0,019 and P = 0,003) out of the total ipsilateral lymph-nodes excised., Conclusions: Lateral wall tumor location at diagnostic TURBT (either right or left side) predicts a higher percentage of ipsilateral positive lymph-nodes s/p RC., Competing Interests: Declaration of competing interest All co-authors have no direct or indirect commercial financial incentive associated with publishing the article. Specifically, no financial support has been received for this research/study. No funding agreement limits our ability to complete and publish our research/study fairly, (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: To evaluate how prostate-specific antigen (PSA) levels decrease after removal of isolated prostate cancer (PCa) nodal metastases in relation to their diameter/volume ("PSA-density of PCa-metastases") and maximum standardized uptake value (SUV max )., Methods: A total of 83 consecutive patients with solitary nodal recurrence after radical prostatectomy who underwent prostate-specific membrane antigen-radioguided salvage surgery were retrospectively analyzed. Using multivariable linear regression models, the PSA-decrease after removal of each PCa-metastases (=PSA-contribution of each PCa-metastases) was correlated with the long axis diameter/estimated volume and the SUV max of each removed metastasis. Sizes were measured by imaging and histopathologic examination., Results: A total of 83 patients were included with a median (interquartile range [IQR]) PSA-decrease of 0.56 [0.22, 1.31] ng/mL after salvage surgery. The median [IQR] long axis diameters in imaging and histopathological examination were 8.0 [6.0, 11.0] mm and 8.4 [5.5, 11.1] mm, respectively. The median [IQR] estimated volumes were 0.13 [0.05, 0.32] cc (imaging) and 0.05 [0.02, 0.17] cc (pathology). In multivariable linear regression analyses, the estimated PSA-contribution ([95% confidence interval [CI]) of each millimeter of long axis diameter was 0.09 [0.03, 0.14] ng/mL (imaging) or 0.08 [0.03, 0.12] ng/mL (histology). The minimum diameter for biochemical recurrence (PSA ≥ 0.2 ng/mL) was >2.2 mm (imaging) or >2.5 mm (histology). The estimated PSA-contribution [95% CI] of each cc cancer volume was 1.23 [0.51, 1.94] ng/mL (imaging) or 1.46 [0.40, 2.52] ng/mL (histology). SUV max as surrogate parameter for tissue composition was associated with increased PSA-contribution of PCa-metastases (+0.03-0.05 ng/mL per unit increase)., Conclusions: The diameter/volume and SUV max of metastatic tissue correlate with its contribution to PSA levels. Therefore, very small metastases may produce too little PSA for biochemical recurrence., (© 2024 The Author(s). The Prostate published by Wiley Periodicals LLC.)

In up to 18% of patients, recurrence is observed after curative radical cystectomy. Tumour recurrence occurs in most cases in the locoregional lymph node, as well as in the remaining urinary tract, but very rarely in the orthotopic neobladder. We report a case of multiple recurrence of urothelial carcinoma solely in the orthotopic neobladder of a male patient, 10 years after surgery, without involvement of the urethra or upper urinary tract. Therefore, the patient underwent resection of the neobladder with conversion to a sigmoid conduit. Nevertheless approximately 6 months later the patient developed widespread metastases and died a few months later. Currently, no guidelines are available for the treatment of these rare cases. We present our experience, together with revision of the current literature on this issue., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Purpose: We sought to investigate predictors of unfavorable tumor upgrading in very favorable intermediate-risk (IR) prostate cancer (PCa) patients treated with robot-assisted radical prostatectomy, in addition to evaluate how it may affect the risk of disease progression., Methods: A very favorable subset of IR PCa patients presenting with prostate-specific antigen (PSA) < 10 ng/mL, percentage of biopsy positive cores (BPC) < 50%, and either International Society of Urological Pathology (ISUP) grade group 1 and clinical stage T2b or ISUP grade group 2 and clinical stage T1c-2b was identified. Unfavorable pathology at radical prostatectomy was defined as the presence of ISUP grade group > 2 (unfavorable tumor upgrading), extracapsular extension (ECE), and seminal vesicle invasion (SVI). Disease progression was defined as the event of biochemical recurrence and/or local recurrence and/or distant metastases. Associations were evaluated by Cox regression and logistic regression analyses., Results: Overall, 210 patients were identified between January 2013 and October 2020. Unfavorable tumor upgrading was detected in 71 (33.8%) cases, and adverse tumor stage, including ECE or SVI in 18 (8.6%) and 11 (5.2%) patients, respectively. Median (interquartile range) follow-up was 38.5 (16-61) months. PCa progression occurred in 24 (11.4%) patients. Very favorable IR PCa patients with unfavorable tumor upgrading at final pathology showed a persistent risk of disease progression, which hold significance after adjustment for all factors (Hazard Ratio [HR]: 5.95, 95% Confidence Interval [CI]: 1.97-17.92, p = 0.002) of which PSA was an independent predictor (HR: 1.52, 95% CI 1.12-2.08, p = 0.008). Moreover, these subjects were more likely to belong to the biopsy ISUP grade group 2., Conclusions: Very favorable IR PCa patients hiding unfavorable tumor upgrading were more likely to experience disease progression. Unfavorable tumor upgrading involved about one-third of cases and was less likely to occur in patients presenting with biopsy ISUP grade group 1. Tumor misclassification is an issue to discuss, when counseling this subset of patients for active surveillance because of the risk of delayed active treatment., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: We assessed the prognostic impact of the 2012 Briganti nomogram on prostate cancer (PCa) progression in intermediate-risk (IR) patients presenting with PSA <10ng/mL, ISUP grade group 3, and clinical stage up to cT2b treated with robot assisted radical prostatectomy eventually associated with extended pelvic lymph node dissection., Materials and Methods: From January 2013 to December 2021, data of surgically treated IR PCa patients were retrospectively evaluated. Only patients presenting with the above-mentioned features were considered. The 2012 Briganti nomogram was assessed either as a continuous and a categorical variable (up to the median, which was detected as 6%, vs. above the median). The association with PCa progression, defined as biochemical recurrence, and/or metastatic progression, was evaluated by Cox proportional hazard regression models., Results: Overall, 147 patients were included. Compared to subjects with a nomogram score up to 6%, those presenting with a score above 6% were more likely to be younger, had larger/palpable tumors, presented with higher PSA, underwent tumor upgrading, harbored non-organ confined disease, and had positive surgical margins at final pathology. PCa progression, which occurred in 32 (21.7%) cases, was independently predicted by the 2012 Briganti nomogram both considered as a continuous (Hazard Ratio [HR]:1.04, 95% Confidence Interval [CI]:1.01-1.08;p=0.021), and a categorical variable (HR:2.32; 95%CI:1.11-4.87;p=0.026), even after adjustment for tumor upgrading., Conclusions: In IR PCa patients with PSA <10ng/mL, ISUP grade group 3, and clinical stage up to cT2b, the 2012 Briganti nomogram independently predicts PCa progression. In this challenging subset of patients, this tool can identify prognostic subgroups, independently by upgrading issues., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Objectives: To assess the prognostic impact and predictors of adverse tumor grade in very favorable low- and intermediate-risk prostate cancer (PCa) patients treated with robot-assisted radical prostatectomy (RARP)., Methods: Data of low- and intermediate PCa risk-class patients were retrieved from a prospectively maintained institutional database. Adverse tumor grade was defined as pathology ISUP grade group > 2. Disease progression was defined as a biochemical recurrence event and/or local recurrence and/or distant metastases. Associations were assessed by Cox's proportional hazards and logistic regression model., Results: Between January 2013 and October 2020, the study evaluated a population of 289 patients, including 178 low-risk cases (61.1%) and 111 intermediate-risk subjects (38.4%); unfavorable tumor grade was detected in 82 cases (28.4%). PCa progression, which occurred in 29 patients (10%), was independently predicted by adverse tumor grade and biopsy ISUP grade group 2, with the former showing stronger associations (hazard ratio, HR = 4.478; 95% CI: 1.840-10.895; p = 0.001) than the latter (HR = 2.336; 95% CI: 1.057-5.164; p = 0.036). Older age and biopsy ISUP grade group 2 were independent clinical predictors of adverse tumor grade, associated with larger tumors that eventually presented non-organ-confined disease., Conclusions: In a very favorable PCa patient population, adverse tumor grade was an unfavorable prognostic factor for disease progression. Active surveillance in very favorable intermediate-risk patients is still a hazard, so molecular and genetic testing of biopsy specimens is needed.

Objectives: We tested whether the 2012 Briganti nomogram for the risk of pelvic lymph node invasion (PLNI) may represent a predictor of disease progression after surgical management in high-risk (HR) prostate cancer (PCa) patients according to the European Association of Urology., Methods: Between January 2013 and December 2021, HR PCa patients treated with robot-assisted radical prostatectomy (RARP) and extended pelvic lymph node dissection (ePLND) were identified. The 2012 Briganti nomogram was evaluated as a continuous and categorical variable, which was dichotomized using the median. The risk of disease progression, defined as the event of biochemical recurrence and/or local recurrence/distant metastases was assessed by Cox regression models., Results: Overall, 204 patients were identified. The median 2012 Briganti nomogram score resulted 12.0% (IQR: 6.0-22.0%). PLNI was detected in 57 (27.9%) cases. Compared to patients who had preoperatively a 2012 Briganti nomogram score ≤12%, those with a score >12% were more likely to present with higher percentage of biopsy positive cores, palpable tumors at digital rectal examination, high-grade cancers at prostate biopsies, and unfavorable pathology in the surgical specimen. At multivariable Cox regression analyses, disease progression, which occurred in 85 (41.7%) patients, was predicted by the 2012 Briganti nomogram score (HR: 1.02; 95%CI: 1.00-1.03; p  = 0.012), independently by tumors presenting as palpable (HR: 1.78; 95%CI: 1.10.2.88; p  = 0.020) or the presence of PLNI in the surgical specimen (HR: 3.73; 95%CI: 2.10-5.13; p  = 0.012)., Conclusions: The 2012 Briganti nomogram represented an independent predictor of adverse prognosis in HR PCa patients treated with RARP and ePLND. As the score increased, so patients were more likely to experience disease progression, independently by the occurrence of PLNI. The association between the nomogram, unfavorable pathology and tumor behavior might turn out to be useful for selecting a subset of patients needing different treatment paradigms in HR disease., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

To evaluate the prognostic potential of the 2012 Briganti nomogram for pelvic lymph node invasion on disease progression after surgery in intermediate-risk (IR) prostate cancer (PCa) patients with favorable tumor grade (International Society of Urological Pathology grade group 1 or 2), eventually associated with adverse clinical features as PSA between 10 and 20 ng/mL and/or clinical stage T2b. All IR PCa patients treated with robot-assisted radical prostatectomy and eventually extended pelvic lymph node dissection at the Department of Urology of the Integrated University Hospital of Verona between 2013 and 2021, with the abovementioned features, and available follow-up were considered. The 2012 Briganti nomogram score was assessed both as a continuous and dichotomous variable, where a mean risk score of 4% was used a threshold. The independent predictor status of the nomogram score on disease progression defined as the occurrence of biochemical recurrence and/or metastatic progression was evaluated using the Cox regression analysis. Overall, 348 patients were enrolled in the study. Median (interquartile range) follow-up was 98 (83.5-112.4) months. At multivariable Cox regression analysis, PCa progression, which occurred in 65 (18.7%) cases, was independently predicted only by the 2012 Briganti nomogram score evaluated as a continuous variable, among all considered clinical features (HR 1.16; 95%CI 1.08-1.24; p < 0.001). In addition, patients presenting with a nomogram score ≥ 4% were more likely to experience disease progression even after adjustment for clinical (HR 2.22, 95%CI 1.02-4.79; p = 0.043) and pathological (HR 1.80; 95%CI 1.06-3.05; p = 0.031) factors. In the examined patient population, the 2012 Briganti nomogram predicted PCa progression after surgery. Accordingly, as the risk score increased, patients were more likely to progress, independently by the occurrence of adverse pathology in the surgical specimen. The 2012 Briganti nomogram score categorized according to the mean value allowed to identify prognostic subgroups., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Background: Treatment outcomes in intermediate-risk prostate cancer (PCa) may be impaired by adverse pathology misclassification including tumor upgrading and upstaging. Clinical predictors of disease progression need to be improved in this category of patients., Objectives: To identify PCa prognostic factors to define prognostic groups in intermediate-risk patients treated with robot-assisted radical prostatectomy (RARP)., Design: Data from 1143 patients undergoing RARP from January 2013 to October 2020 were collected: 901 subjects had available follow-up, of whom 479 were at intermediate risk., Methods: PCa progression was defined as biochemical recurrence and/or local recurrence and/or distant metastases. Study endpoints were evaluated by statistical methods including Cox's proportional hazards, Kaplan-Meyer survival curves, and binomial and multinomial logistic regression models., Results: After a median (interquartile range) of 35 months (15-57 months), 84 patients (17.5%) had disease progression, which was independently predicted by the percentage of biopsy-positive cores ⩾ 50% and the International Society of Urological Pathology (ISUP) grade group 3 for clinical factors and by ISUP > 2, positive surgical margins and pelvic lymph node invasion for pathological features. Patients were classified into clinical and pathological groups as favorable, unfavorable (one prognostic factor), and adverse (more than one prognostic factor). The risk of PCa progression increased with worsening prognosis through groups. A significant positive association was found between the two groups; consequently, as clinical prognosis worsened, the risk of detecting unfavorable and adverse pathological prognostic clusters increased in both unadjusted and adjusted models., Conclusion: The study identified factors predicting disease progression that allowed the computation of highly correlated prognostic groups. As the prognosis worsened, the risk of PCa progression increased. Intermediate-risk PCa needs more prognostic stratification for appropriate management., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Objective: To evaluate the influence of endogenous testosterone density (ETD) and tumor load density (TLD) in the surgical specimen of prostate cancer (PCa) patients., Methods: ETD was assessed as the ratio of endogenous testosterone (ET) to prostate volume (PV). TLD was calculated as the ratio of tumor load (TL) to prostate weight. Preoperative prostate-specific antigen relative densities (PSAD) and percentage of biopsy-positive cores (BPCD) were also assessed. The association of high TLD (above the first quartile) with clinical and pathological factors was assessed by the logistic regression model (univariate and multivariate analysis)., Results: Between November 2014 and December 2019, ET was measured in 805 cases treated with radical prostatectomy (RP). Median (IQR) of ET and ETD was 412 (321.4-519 ng/dL) and 9.8 (6.8-14.4 ng/(dLxmL)) as well as for TL and TLD was 20 (10-30%) and 0.33 (0.17-0.58%/gr), respectively. As a result, high TLD was detected in 75% of cases. A positive independent association was found between high TLD and ETD. Accordingly, as ETD levels increased, the risk of detecting high TLD in the surgical specimen increased, regardless of PSAD and BPCD., Conclusions: At diagnosis of PCa, a positive independent association was found between ETD and risk of high TLD. Subjects with increasing ETD levels were more likely to have high TLD, associated with unfavorable pathology features. The positive association between ETD and TLD in the prostate microenvironment might adversely influence PCa's natural history., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: We tested the association between functional impairment in activities of daily living (ADL) assessed through the Barthel Index (BI), and oncological outcomes following radical cystectomy (RC) for bladder cancer (BCa)., Patients and Methods: We retrospectively analyzed data of 262 clinically nonmetastatic BCa patients, who underwent RC between 2015 and 2022, with available follow-up. According to preoperative BI, patients were divided in 2 groups: BI ≤90 (moderate/severe/total dependency in ADL) versus BI 95 to 100 (slight dependency/independency in ADL). Kaplan-Meier plots compared disease recurrence (DR)-, cancer-specific mortality (CSM)-, and overall mortality (OM)-free survival according to established categories. Multivariable Cox regression models tested the BI as an independent predictor of oncological outcomes., Results: According to the BI, the patient cohort was distributed as follows: 19% (n = 50) BI ≤90 versus 81% (n = 212) BI 95-100. Compared to patients with BI 95 to 100, patients with BI ≤90 were less likely to receive intravesical immuno- or chemotherapy (18% vs. 34%, p = .028), and more frequently underwent less complex urinary diversion as ureterocutaneostomy (36% vs. 9%, p < .001), or harbored muscle-invasive BCa at final pathology (72% vs. 56%, p = .043). In multivariable Cox regression models adjusted for age, ASA physical status score, pathological T and N stage, and surgical margins status, BI ≤90 independently predicted higher DR (HR [hazard ratio]:2.00, 95%CI [confidence interval]:1.21-3.30, p = .007), CSM (HR:2.70, 95%CI:1.48-4.90, p = .001), and OM (HR:2.09, 95%CI:1.28-3.43, p = .003)., Conclusion: Preoperative impairment in ADL was associated with adverse oncological outcomes following RC for BCa. The integration of the BI into clinical practice may improve the risk assessment of BCa patients candidates to RC., Competing Interests: Disclosure The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: This study aimed to evaluate the impact of palpable prostate tumors on digital rectal exam (DRE) on the disease progression of prostate cancer (PCa) treated with RARP surgery in a tertiary referral center., Materials and Methods: Overall, 901 patients were evaluated in a period ranging from January 2013 to October 2020. In the surgical specimen, unfavorable pathology included ISUP grade group ≥3, seminal vesicle invasion (SVI), and pelvic lymph node invasion (PLNI). Disease progression was defined as the occurrence of biochemical recurrence and/or local recurrence and/or distant metastases; its association with the primary endpoint was evaluated by Cox's proportional model., Results: Palpable prostate tumors were detected in 359 (39.8%) patients. The overall median (IQR) follow-up was 40 months (17-59). PCa progressed in 159 cases (17.6%). Nodularity or induration of the prostate at DRE was significantly associated with features of unfavorable pathology, increased risk of PCa progression (hazard ratio, HR = 1.902; 95% CI: 1.389-2.605; p < 0.0001) and, on multivariable analysis, was an independent prognostic factor for disease progression after adjusting for clinical and pathological variables., Conclusions: Prostate tumors presenting with an abnormal DRE finding have an independent adverse outcome for disease progression after PCa surgery. They provide also independent prognostic information, as they may be more aggressive than impalpable PCa., (© 2023. The Author(s).)

Objectives: This study aimed to assess more clinical and pathological factors associated with prostate cancer (PCa) progression in high-risk PCa patients treated primarily with robot-assisted radical prostatectomy (RARP) and extended pelvic lymph node dissection (ePLND) in a tertiary referral center., Materials and Methods: In a period ranging from January 2013 to October 2020, RARP and ePLND were performed on 180 high-risk patients at Azienda Ospedaliera Universitaria Integrata of Verona (Italy). PCa progression was defined as biochemical recurrence/persistence and/or local recurrence and/or distant metastases. Statistical methods evaluated study endpoints, including Cox's proportional hazards, Kaplan-Meyer survival curves, and binomial logistic regression models., Results: The median age of included patients was 66.5 [62-71] years. Disease progression occurred in 55 patients (30.6%), who were more likely to have advanced age, palpable tumors, and unfavorable pathologic features, including high tumor grade, stage, and pelvic lymph node invasion (PLNI). On multivariate analysis, PCa progression was predicted by advanced age (≥ 70 years) (HR = 2.183; 95% CI = 1.089-4377, p = 0.028), palpable tumors (HR = 3.113; 95% CI = 1.499-6.465), p = 0.002), and PLNI (HR = 2.945; 95% CI = 1.441-6.018, p = 0.003), which were associated with clinical standard factors defining high-risk PCa. Age had a negative prognostic impact on elderly patients, who were less likely to have palpable tumors but more likely to have high-grade tumors., Conclusions: High-risk PCa progression was independently predicted by advanced age, palpable tumors, and PLNI, which is associated with standard clinical prognostic factors. Consequently, with increasing age, the prognosis is worse in elderly patients, who represent an unfavorable age group that needs extensive counseling for appropriate and personalized management decisions., (© 2023. The Author(s).)

We tested the association between endogenous testosterone density (ETD; the ratio between endogenous testosterone [ET] and prostate volume) and prostate cancer (PCa) aggressiveness in very favorable low- and intermediate-risk PCa patients who underwent radical prostatectomy (RP). Only patients with prostate-specific antigen (PSA) within 10 ng ml -1 , clinical stage T1c, and International Society of Urological Pathology (ISUP) grade group 1 or 2 were included. Preoperative ET levels up to 350 ng dl -1 were classified as abnormal. Tumor quantitation density factors were evaluated as the ratio between percentage of biopsy-positive cores and prostate volume (biopsy-positive cores density, BPCD) and the ratio between percentage of cancer invasion at final pathology and prostate weight (tumor load density, TLD). Disease upgrading was coded as ISUP grade group >2, and progression as recurrence (biochemical and/or local and/or distant). Risk associations were evaluated by multivariable Cox and logistic regression models. Of 320 patients, 151 (47.2%) had intermediate-risk PCa. ET (median: 402.3 ng dl -1 ) resulted abnormal in 111 (34.7%) cases (median ETD: 9.8 ng dl -1 ml -1 ). Upgrading and progression occurred in 109 (34.1%) and 32 (10.6%) cases, respectively. Progression was predicted by ISUP grade group 2 (hazard ratio [HR]: 2.290; P = 0.029) and upgrading (HR: 3.098; P = 0.003), which was associated with ISUP grade group 2 (odds ratio [OR]: 1.785; P = 0.017) and TLD above the median (OR: 2.261; P = 0.001). After adjustment for PSA density and body mass index (BMI), ETD above the median was positively associated with BPCD (OR: 3.404; P < 0.001) and TLD (OR: 5.238; P < 0.001). Notably, subjects with abnormal ET were more likely to have higher BPCD (OR: 5.566; P = 0.002), as well as TLD (OR: 14.998; P = 0.016). Independently by routinely evaluated factors, as ETD increased, BPCD and TLD increased, but increments were higher for abnormal ET levels. In very favorable cohorts, ETD may further stratify the risk of aggressive PCa., (Copyright © 2023 Copyright: © The Author(s)(2023).)

Background: Since before the COVID-19 pandemic, hospital-acquired infections (HAIs) represented a global healthcare crisis. Few studies suggested that COVID-19-related basic hygiene measures (BHM) could lower HAIs rates, reaching inconclusive results. The aim of this study was to investigate the hypothetical benefit on HAIs rate of COVID-19-enhanced BHM systematic introduction after major elective urological surgery., Methods: Since the pandemic began, our hospital has implemented BHM to limit the spread of COVID-19. We compared patients operated in the pre-COVID-19 era (no-BHM period) with those operated after the pandemic started (BHM period). Outcomes were the incidence of HAIs and postoperative complications, and the length of hospital stay (LOS). Two balanced groups were generated by propensity score 1:1 matching., Results: Of 1053 major urological interventions, 604 were performed in the no-BHM period, and 449 in the BHM period. After matched analysis, the comparison groups consisted of 310 patients each. Of 107 recorded HAIs, 43 occurred during the BHM period (13.9%), and 64 during the no-BHM period (20.7%), with a statistically significant difference in multivariable analysis (OR 0.5 [95% CI 0.3-0.8], P=0.004). Postoperative complications rate was significantly lower in the BHM period than in the no-BHM period (29.0% versus 36.5%, OR 0.6 [95% CI 0.4-0.9], P=0.01). The LOS differed significantly between BHM and no-BHM periods: a median of 5 (5-8) days versus 6 (5-8), respectively (P<0.001)., Conclusions: The risk of infections, postoperative complications, and prolonged LOS after major urological surgery was significantly reduced with the systematic introduction of COVID-19-related BHM, their application could, therefore, be prolonged with lasting benefits.

Purpose: To test the role of endogenous total testosterone (ETT) as a predictor of prostate cancer (PCa) progression in patients treated with robot assisted radical prostatectomy for clinically localized disease., Methods: Between November 2014 and December 2019, 580 consecutive patients were evaluated. Preoperative ETT levels were classified as ≤ 350 ng/dL vs. > 350 ng/dL. The associations between ETT levels and the risk of PCa progression, defined as any event of biochemical recurrence and/or local recurrence and/or distant metastases, or other clinical and pathological factors were evaluated by regression analyses., Results: Preoperative ETT levels resulted ≤ 350 ng/dL in 173 (29.8%) patients. Disease progression occurred in 101 (17.1%) cases. Progressing patients were more likely to present with PSA levels > 10 ng/mL, as well as with unfavorable tumor grade (ISUP 4-5) and stage (pT3b) at final pathology, but less likely to have ETT levels ≤ 350 ng/mL. On clinical multivariable Cox regression models, ETT ≤ 350 ng/mL exhibited a statistically significant protective effect on tumor progression (hazard ratio: 0.57, p = 0.013). Subjects presenting with ETT levels ≤ 350 ng/mL were less likely to harbor ISUP 4-5 tumor grade either at biopsy (odds ratio [OR]: 0.46, p = 0.028) or final pathology (OR: 0.45, p = 0.032)., Conclusions: At PCa diagnosis, ETT, which associates with ISUP tumor grade, is an independent predictor of disease progression. Accordingly, as ETT decreases to levels ≤ 350 ng/dL, the risk of unfavorable tumor grade decreases, and a more favorable prognosis is expected. Preoperative ETT levels may allow further patient stratification along prognostic risk groups., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Objectives: To investigate the association between Barthel Index (BI), which measures level of patients independence during daily living activities (ADL), and perioperative outcomes in a large cohort of consecutive bladder cancer (BCa) patients, who underwent radical cystectomy (RC) at a tertiary referral center., Methods: We retrospectively evaluated data from clinically nonmetastatic BCa patients treated with RC between 2015 and 2022. For each patient, BI was assessed preoperatively. According to BI score, patients were divided into three groups: ≤60 (total/severe dependency) vs. 65-90 (moderate dependency) vs. 95-100 (slight dependency/independency). Regression analyses tested the association between BI score and major postoperative complications (Clavien-Dindo >2), length of in-hospital stay (LOHS), 90-days readmission, and total costs., Results: Overall, 288 patients were included. According to BI score, the patient cohort was distributed as follows: 4% (n = 11) BI ≤60 vs. 15% (n = 42) BI 65-90 vs. 81% (n = 235) BI 95-100. Patients with BI ≤60 had more frequent ureterocutaneostomy performed, shorter operative time, higher rates of postoperative complications, longer LOHS, higher rates of readmission, and were associated with higher total costs, compared to patients with BI 65-90 and 95-100. In multivariable regression models, BI ≤60 remained an independent predictor of increased risk of major postoperative complications (odds ratio: 6.62, p = 0.006), longer LOHS (rate ratio: 1.25, p < 0.001), and higher costs (β: 2.617, p = 0.038)., Conclusions: Total/severe dependency in ADL assessed by BI was associated with higher rates of major postoperative complications, longer hospitalization, and higher costs in BCa patients treated with RC. BI assessment should be considered during patients selection process and counseling before surgery., (© 2022 The Japanese Urological Association.)

Background: The impact of senior age on prostate cancer (PCa) oncological outcomes following radical prostatectomy (RP) is controversial, and further clinical factors could help stratifying risk categories in these patients., Objective: We tested the association between endogenous testosterone (ET) and risk of PCa progression in elderly patients treated with RP., Design: Data from PCa patients treated with RP at a single tertiary referral center, between November 2014 and December 2019 with available follow-up, were retrospectively evaluated., Methods: Preoperative ET (classified as normal if >350 ng/dl) was measured for each patient. Patients were divided according to a cut-off age of 70 years. Unfavorable pathology consisted of International Society of Urologic Pathology (ISUP) grade group >2, seminal vesicle, and pelvic lymph node invasion. Cox regression models tested the association between clinical/pathological tumor features and risk of PCa progression in each age subgroup., Results: Of 651 included patients, 190 (29.2%) were elderly. Abnormal ET levels were detected in 195 (30.0%) cases. Compared with their younger counterparts, elderly patients were more likely to have pathological ISUP grade group >2 (49.0% versus 63.2%). Disease progression occurred in 108 (16.6%) cases with no statistically significant difference between age subgroups. Among the elderly, clinically progressing patients were more likely to have normal ET levels (77.4% versus 67.9%) and unfavorable tumor grades (90.3% versus 57.9%) than patients who did not progress. In multivariable Cox regression models, normal ET [hazard ratio (HR) = 3.29; 95% confidence interval (CI) = 1.27-8.55; p  = 0.014] and pathological ISUP grade group >2 (HR = 5.62; 95% CI = 1.60-19.79; p  = 0.007) were independent predictors of PCa progression. On clinical multivariable models, elderly patients were more likely to progress for normal ET levels (HR = 3.42; 95% CI = 1.34-8.70; p  = 0.010), independently by belonging to high-risk category. Elderly patients with normal ET progressed more rapidly than those with abnormal ET., Conclusion: In elderly patients, normal preoperative ET independently predicted PCa progression. Elderly patients with normal ET progressed more rapidly than controls, suggesting that longer exposure time to high-grade tumors could adversely impact sequential cancer mutations, where normal ET is not anymore protective on disease progression., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2023.)

We report a case of a 83-year-old woman with the initial diagnosis of an occult invasive lobular breast carcinoma due to gastrointestinal metastasis with an entervesical fistula., Competing Interests: E. Comploj, E. Hanspeter, M. Bonatti, S. Palermo, G. Mazzucato, A. Pycha, E. Trenti geben an, dass kein Interessenkonflikt besteht und die ethischen Richtlinien eingehalten wurden., (Thieme. All rights reserved.)

Objective: To investigate endogenous testosterone density (ETD) predicting disease progression from clinically localized impalpable prostate cancer (PCa) presenting with prostate-specific antigen (PSA) levels elevated up to 10 ng/mL and treated with radical prostatectomy., Materials and Methods: In a period ranging from November 2014 to December 2019, 805 consecutive PCa patients who were not under androgen blockade had endogenous testosterone (ET, ng/dL) measured before surgery. ETD was evaluated as the ratio of ET on prostate volume (PV). Unfavorable disease was defined as including ISUP ≥ 3 and/or seminal vesicle invasion in the surgical specimen. The risk of disease progression was evaluated by statistical methods., Results: Overall, the study selected 433 patients, of whom 353 (81.5%) had available follow-up. Unfavorable disease occurred in 46.7% of cases and was predicted by tumor quantitation features that were positively associated with ETD. Disease progression, which occurred for 46 (13%) cases, was independently predicted only by ETD (hazard ratio, HR = 1.037; 95% CI 1.004-1.072; p = 0.030) after adjusting for unfavorable disease. According to a multivariate model, ETD above the third quartile was confirmed to be an independent predictor for PCa progression (HR = 2.479; 95% CI 1.355-4.534; p = 0.003) after adjusting for unfavorable disease. The same ETD measurements, ET mean levels were significantly lower in progressing cancers., Conclusions: In this particular subset of patients, increased ETD with low ET levels, indicating androgen independence, resulted in a more aggressive disease with poorer prognosis., (© 2022. The Author(s).)

Objectives: We investigated AB0 blood groups prevalence according to preoperative and pathological tumor characteristics, and their association with oncological outcomes, and renal function decline in a contemporary large cohort of bladder cancer (BCa) patients, who underwent radical cystectomy (RC) at a tertiary referral center., Materials and Methods: We retrospectively evaluated data of patients with histologically confirmed and clinically non metastatic BCa, who underwent RC between 2014 and 2021 at our Institution. Kaplan-Meier (KM) plots and Cox regression (CR) models tested the relationship between AB0 blood groups and local recurrence-, metastasis-, cancer specific mortality-, and overall mortality-free survival. Logistic regression (LR) models tested the association between AB0 blood groups and renal function decline, defined as an estimated Glomerular Filtration Rate (eGFR) < 60 mL/min, at post-operative day 1, discharge and 6- months of follow-up., Results: Of 301 included patients, 128 (42.5%) had group A, 126 (41.9%) had group 0, 28 (9.3%) had group B, and 19 (6.3%) had group AB. Patients with group 0 developed higher rates of muscle- invasive BCa (p = 0.028) with high-grade features (p = 0.005) at last bladder resection, and less frequently received preoperative immunotherapy with Bacillus of Calmette-Guerin (p = 0.044), than their non-0 counterparts. Additionally, these patients harbored more advanced pathologic tumor stage at RC (p = 0.024). KM plots showed no differences among all tested cancer control outcomes between AB0 blood groups (p > 0.05 in all cases). Patients with group AB presented the lowest median eGFR at each time point. In multivariable LR analyses addressing renal function decline, group AB was independently associated with eGFR< 60 mL/min at discharge (Odds Ratio: 4.28, p = 0.047)., Conclusions: Among AB0 blood groups, patients with group 0 exhibited the most aggressive tumor profile. However, no differences were recorded in recurrence or survival rates. Group AB independently predicted renal function decline at discharge.

Objective: to evaluate predictors and the prognostic impact of favorable vs. unfavorable tumor upgrading among low-risk prostate cancer (LR PCa) patients treated with robot-assisted radical prostatectomy (RARP). Methods: From January 2013 to October 2020, LR PCa patients treated with RARP at our institution were identified. Unfavorable tumor upgrading was defined as the presence of an International Society of Urological Pathology (ISUP) grade group at final pathology > 2. Disease relapse was coded as biochemical recurrence and/or local recurrence and/or presence of distant metastases. Regression analyses tested the association between clinical and pathological features and the risk of unfavorable tumor upgrading and disease relapse. Results: Of the 237 total LR PCa patients, 60 (25.3%) harbored unfavorable tumor upgrading. Disease relapse occurred in 20 (8.4%) patients. Unfavorable upgrading represented an independent predictor of disease relapse, even after adjustment for other clinical and pathological variables. Conversely, favorable tumor upgrading did not show any statistically significant association with PCa relapse. Unfavorable tumor upgrading was associated with tumors being larger (OR: 1.03; p = 0.031), tumors extending beyond the gland (OR: 8.54, p < 0.001), age (OR: 1.07, p = 0.009), and PSA density (PSAD) ≥ 0.15 ng/mL/cc (OR: 1.07, p = 0.009). Conclusions: LR PCa patients with unfavorable upgrading at final pathology were more likely to be older, to have PSAD ≥ 0.15 ng/mL/cc, and to experience disease relapse. Unfavorable tumor upgrading is an issue to consider when counseling these patients to avoid delayed treatments, which may impair cancer-specific survival.

Introduction and Objective: Although advanced age doesn't seem to impair oncological outcomes after robot-assisted radical prostatectomy (RARP), elderly patients have increased rates of prostate cancer (PCa) related deaths due to a higher incidence of high-risk disease. The potential unfavorable impact of advanced age on oncological outcomes following RARP remains an unsettled issue. We aimed to evaluate the oncological outcome of PCa patients > 69 years old in a single tertiary center., Materials and Methods: 1143 patients with clinically localized PCa underwent RARP from January 2013 to October 2020. Analysis was performed on 901 patients with available follow-up. Patients ≥ 70 years old were considered elderly. Unfavorable pathology included ISUP grade group > 2, seminal vesicle, and pelvic lymph node invasion. Disease progression was defined as biochemical and/or local recurrence and/or distant metastases., Results: 243 cases (27%) were classified as elderly patients (median age 72 years). Median (IQR) follow-up was 40.4 (38.7-42.2) months. Disease progression occurred in 159 cases (17.6%). Elderly patients were more likely to belong to EAU high-risk class, have unfavorable pathology, and experience disease progression after surgery (HR = 5.300; 95% CI 1.844-15.237; p = 0.002) compared to the younger patients., Conclusions: Elderly patients eligible for RARP are more likely to belong to the EAU high-risk category and to have unfavorable pathology that are independent predictors of disease progression. Advanced age adversely impacts on oncological outcomes when evaluated inside these unfavorable categories. Accordingly, elderly patients belonging to the EAU high-risk should be counseled about the increased risk of disease progression after surgery., (© 2022. The Author(s).)

Objective: To evaluate the influence of endogenous testosterone density (ETD) on pelvic lymph node invasion (PLNI) in high risk (HR) prostate cancer (PCa) treated with radical prostatectomy (RP) and staged with extended pelvic lymph node dissection (ePLND)., Materials and Methods: ETD was evaluated as the ratio of endogenous testosterone (ET) on prostate volume (PV). HR-PCa was assessed according to the European Association of Urology (EAU) system. The association of ETD and other routinely clinical factors (BPC: percentage of biopsy positive cores; PSA: prostate specific antigen; ISUP: tumor grade system according to the International Society of Urologic Pathology; cT: tumor clinical stage) with the risk of PLNI was assessed by the logistic regression model., Results: Overall, 201 out of 805 patients (24.9%) were classified HR and PLNI occurred in 42 subjects (20.9%). On multivariate analysis, PLNI was independently predicted by BPC (OR 1.020; 95% CI 1.006-1.035; p = 0.019), ISUP > 3 (OR 2.621; 95% CI 1.170-5.869; p = 0.019) and ETD (OR 0.932; 95% CI 0.870-0.999; p = 0.045). After categorizing continuous clinical predictors, the risk of PLNI was independently increased by ETD up to the median (OR 2.379; 95% CI 1.134-4.991; p = 0.022), BPC > 50% (OR 3.125; 95% CI 1.520-6.425; p = 0.002) as well as by ISUP > 3 (OR 2.219; 95% CI 1.031-4.776; p = 0.042)., Conclusions: As ETD measurements decreased, patients were more likely to have PLNI. In HR disease with PLNI, the influence of PCa on ETD should be addressed by higher level studies., (© 2022. The Author(s).)

Introduction: Pain management of patients with chronic pelvic pain syndrome (CPPS) is challenging, because pain is often refractory to conventional treatments. Botulinum toxin A (BTX-A) may represent a promising therapeutic strategy for these patients. The aim of this systematic review was to investigate the role of BTX-A in CPPS treatment., Methods: We reviewed the literature for prospective studies evaluating the use of BTX-A in the treatment of CPPS. A comprehensive search in the PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases was performed from English language articles published between January 2000 and October 2021. The primary outcome was to evaluate pain improvement in CPPS after BTX-A treatment. Pooled meta-analysis of the included studies, considering the effect of BTX-A on pain evaluated at last available follow-up compared to baseline values, was performed together with meta-regression analysis., Results: After screening 1001 records, 18 full-text manuscripts were selected, comprising 13 randomized clinical trials and five comparative studies. They covered overall 896 patients of both sexes and several subtype of CPPS (interstitial cystitis/bladder pain syndrome, chronic prostatitis/prostate pain syndrome, chronic scrotal pain, gynecological pelvic pain, myofascial pelvic pain). The clinical and methodological heterogeneity of studies included makes it difficult to do an overall estimation of the real effect of BTX-A on pain and other functional outcomes of various CPPS subtypes. However, considering pooled meta-analysis results, a benefit in pain relief was showed for BTX-A-treated patients both in the overall studies populations and in the overall cohorts of patients with CPP due to bladder, prostate, and gynecological origin., Conclusions: BTX-A could be an efficacious treatment for some specific CPPS subtypes. Higher level studies are needed to assess the efficacy and safety of BTX-A and provide objective indications for its use in CPPS management.

Recent technological advances in molecular biology have led to great progress in the knowledge of structure and function of cells and their main constituents. In this setting, 'omics' is standing out in order to significantly improve the understanding of etiopathogenetic mechanisms of disease and contribute to the development of new biochemical diagnostics and therapeutic tools. 'Omics' indicates the scientific branches investigating every aspect of cell's biology, including structures, functions and dynamics pathways. The main 'omics' are genomics, epigenomics, proteomics, transcriptomics, metabolomics and radiomics. Their diffusion, success and proliferation, addressed to many research fields, has led to many important acquisitions, even in Urology. Aim of this narrative review is to define the state of art of 'omics' application in Urology, describing the most recent and relevant findings, in both oncological and non-oncological diseases, focusing the attention on urinary tract infectious, interstitial cystitis, urolithiasis, prostate cancer, bladder cancer and renal cell carcinoma. In Urology the majority of 'omics' applications regard the pathogenesis and diagnosis of the investigated diseases. In future, its role should be implemented in order to develop specific predictors and tailored treatments.