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Background: Non-Hispanic Black (NHB) men are at higher risk both for incidence and mortality from prostate cancer (PCa) compared to Non-Hispanic White (NHW) men, but these findings arise from biopsy-detected PCa reports. We aimed to compare the incidence, subsequent management and cancer-specific mortality (CSM) of incidental PCa among NHB and NHW men, using two different North American cohorts., Methods: The Surveillance, Epidemiology and End-Result (SEER: 2004-2017) and our institutional Henry Ford Health (HFH: 1995-2022) databases were queried to identify men diagnosed with incidental PCa. Cumulative incidence estimates were used to calculate CSM differences between NHB and NHW men. Competing-risk multivariable regression analysis tested the impact of race on CSM, after accounting for all available covariates., Results: A total of 418 and 6,124 incidental PCa cases were recorded in HFH and SEER database respectively. No pathological differences were observed between NHB and NHW men in both the cohorts, except for prostate-specific antigen (PSA) value at diagnosis, which was higher in NHB men. At 10-years, the CSM rates were 5.5% vs 7.2% in our cohort and 8.6% vs 10.3% in the SEER cohort for NHW and NHB men, respectively (all Gray's test p-value > 0.05). At multivariable, race was not an independent predictor of CSM in our HFH cohort (HR: 1.46, 95% CI: 0.57-3.71, p = 0.6). In the SEER cohort, NHB men were 34% less likely to die from PCa from 1 year to the next (95% CI: 0.49-0.90, p = 0.008), when compared with NHW men., Conclusions: In the comparison of incidental PCa findings between NHB and NHW men, both groups had similar pathological characteristic and survival outcomes. These findings are different from the 'conventional' screening-detected PCa and suggest that racial differences have minimal to no adverse effects on PCa-specific mortality after incidental diagnosis., (© 2024 Wiley Periodicals LLC.)

Purpose: The objective of this manuscript is to assess the effect of varicocele repair (VR) in patients with clinical varicoceles on serum total testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and inhibin B serum levels., Materials and Methods: The study was performed in compliance with the Meta-Analysis and Systematic Reviews of Observational Studies (MOOSE) guidelines and the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). All eligible studies were selected following the PICOS (Population, Intervention, Comparison/Comparator, Outcomes, Study design) model. The values of each outcome measured after VR were compared to the before parameters and, when available, to the values on patients with unrepaired varicocele, and to those of healthy controls with no varicocele. For total testosterone, the values were sub-analyzed based on the mean total testosterone levels before VR (<300 ng/dL or >300 ng/dL), the fertility status, the time of follow-up and the technique used for VR., Results: From a total of 460 abstracts retrieved, 48 articles were included in our meta-analysis. Serum total testosterone levels were significantly higher after VR compared to both pre-treatment levels (mean difference [MD] 82.45 ng/dL, 95% confidence interval [CI]: 64.14-100.76; p<0.00001) and to the levels of patients with unrepaired varicocele (MD 91.64 ng/dL, 95% CI: 62.30-120.99; p<0.00001). They did not differ from the levels of healthy controls with no varicocele (MD -22.01 ng/dL, 95% CI: -68.59-24.58; p=0.35). The increase resulted to be independent from the mean total testosterone levels before VR, fertility status, time of follow-up and type of VR. After VR, a trend toward lower serum LH levels was found compared to before values (MD -0.37 IU/L, 95% CI: -0.74-0.01; p=0.06). When compared to the levels of patients with unrepaired VR, LH levels after VR were significantly lower (MD -0.96 IU/L, 95% CI: -1.56 to -0.35; p=0.002). LH levels were not significantly higher than healthy men without varicocele (MD 0.84 IU/L, 95% CI: -0.68-2.36; p=0.28). Patients with VR had significantly lower FSH levels compared to their pre-treatment values (MD -1.43 IU/L, 95% CI: -1.82 to -1.04; p<0.00001), and also to those of patients with non-repaired varicocele (MD -2.35 IU/L, 95% CI: -4.06 to -0.65; p=0.007). When compared to healthy controls with no varicocele, FSH levels were significantly higher (MD 2.71 IU/L, 95% CI: 1.12-4.31; p=0.0009). Lastly, after VR no significant change in inhibin B serum levels was seen compared to pre-treatment levels (MD 11.76 pg/mL, 95% CI: -3.83-27.35; p=0.14)., Conclusions: The present meta-analysis is the largest to date to assess the impact of VR on Leydig cell and Sertoli cell function using a before-after analysis for uncontrolled studies, and using data from patients with unrepaired varicoceles or healthy patients without varicocele as controls. VR was found to increase and restore to normality serum levels of total testosterone and LH. This evidence could be of value in considering the treatment of varicocele in patients with low testosterone or those who show a progressive decline in testosterone levels., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Purpose: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations., Materials and Methods: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 countries were analyzed descriptively, with a Delphi process used for expert recommendations., Results: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoospermia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differentiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate., Conclusions: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Background and Objective: The preferable technique for orthotopic bladder substitution after radical cystectomy is debated. The aim of this study was to describe our technique of a stapled W-shaped ileal neobladder and assess the complications and functional results in 100 patients. treated from December 2009 to July 2022., Methods: The W-shaped ileal neobladder is created with lateral arms of 15 cm and central arms of 10 cm. Following an incision of the lower part of the two medial arms, a 10-cm GIA titanium stapler is used to detubularize the medial arms first and then the laterals to the medial arms. Urethral-neobladder anastomosis and end-to-end ureteroileal anastomosis are finally carried out. We reported on clinical data, complications, and urinary function outcomes assessed by the International Consultation on Incontinence Questionnaire (ICIQ)-Short Form and daytime/24-h pad test. Full urinary continence (UC) was defined as pad tests yielding 0 g., Key Findings and Limitations: The median surgical time was 210 min. The early (up to 90 d) and late (>90 d) complication rates were 18% (2% grade ≥4) and 11.7% (2% grade ≥4), respectively. Two patients had "late" bladder stones due to chronic urinary retention, whereas none developed calcifications in the neobladder along the stapling lines. Daytime and 24-h UC rates were 74.7% and 72.4% at 12 mo, 82.7% and 72.4% at 36 mo, respectively. Median ICIQ scores were in line with pad test results, being 0 in patients with full UC., Conclusions and Clinical Implications: Our stapled W-shaped ileal neobladder technique was found to be simple and fast to shape, with a low complication rate, and yielded favorable long-term functional outcomes., Patient Summary: This study details the surgical technique, complications, and functional outcomes of patients who underwent open cystectomy with a stapled W-shaped ileal neobladder. Our results indicate that this approach is safe and provides favorable long-term functional outcomes., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Comparative effectiveness studies comparing trimodal therapy (TMT) to radical cystectomy (RC) are typically hindered by selection bias where TMT is usually reserved to patients with poor overall health status. We developed a novel approach by matching patients based on their calculated other-cause mortality (OCM) risk. Using this homogeneous cohort, we tested the impact of TMT vs RC on cancer-specific mortality (CSM)., Materials and Methods: The Surveillance, Epidemiology and End Results (SEER) 2004-2018 database was queried to identify patients diagnosed with cT2-4N0M0 muscle-invasive bladder cancer (MIBC). A Fine-Gray competing-risk regression model calculating the 5-year OCM risk was used to create a 1:1 propensity-score matched-cohort of patients treated with RC or TMT. Cumulative incidence and competing-risk regression analyses tested the impact of treatment type (RC vs TMT) on CSM. Patients were further stratified according to clinical T stage (cT2 vs cT3-4) in sensitivity analyses., Results: We identified 6,587 patients (76%) treated with RC and 2,057 (24%) with TMT. The median follow-up was 3.0 years. In the unmatched-cohort, 5-year OCM and CSM rates were 14% and 40% for RC vs 23% and 47% in TMT group, respectively (all P < 0.001). Our matched-cohort included 4,074 patients, equally distributed for treatment type, with no difference in 5-year OCM (HR: 0.98, 95% CI: 0.86-1.11, P = 0.714). In clinical-stage specific sensitivity analyses, 5-year CSM rate was significantly worse for cT2N0M0 patients treated with TMT (HR: 1.52, 95% CI: 1.21-1.91, P < 0.001) than those treated with RC. For cT3-4N0M0 patients, there was no difference in CSM among the 2 approaches (HR: 0.98, 95% CI: 0.63-1.52, P = 0.900)., Conclusions: Our findings demonstrate an oncologic advantage of RC over TMT for cT2 MIBC patients. Conversely, we did not find a cancer-specific survival difference for cT3-T4 MIBC patients, regardless of treatment., Competing Interests: Declaration of competing interest None of the authors have any relevant disclosures, and none of the authors have any financial or nonfinancial interests that may be relevant to the submitted work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Evaluate the detection rates of systematic, targeted and combined cores at biopsy according to tumor positions in biopsy-naïve patients., Material and Methods: A retrospective analysis of a single-center patient cohort (n = 501) that underwent transrectal prostate biopsy between January 2017 and December 2019 was performed. Multi-parametric MRI was executed as a prebiopsy investigation. Biopsy protocol included, for each patient, 12 systematic cores plus 3 to 5 targeted cores per lesion identified at the mpMRI. Pearson and McNemar chi-squared tests were used for statistical analysis to compare tumor location-related detection rates of systematic, targeted and combined (systematic + targeted) cores at biopsy., Results: Median age of patients was 70 years (IQR 62-72), with a median PSA of 8.5 ng/ml (IQR 5.7-15.6). Positive biopsies were obtained in 67.7% of cases. Overall, targeted cores obtained higher detection rates compared to systematic cores (54.3% vs. 43.1%, p < 0.0001). Differences in detection rates were, however, higher for tumors located at the apex (61.1% vs. 26.3%, p < 0.05) and anteriorly (44.4% vs. 19.3%, p < 0.05). Targeted cores similarly obtained higher detection rates in the posterior zone of the prostate gland for clinically significant prostate cancer. A poor agreement was reported between targeted and systematic cores for the apex and anterior zone of the prostate with, respectively κ = 0.028 and κ = -0.018., Conclusion: A combined approach of targeted and systematic biopsy delivers the highest detection rate in prostate cancer (PCa). The location of the tumor could however greatly influence overall detection rates, indicating the possibility to omit (as for the base or posterior zone of the gland) or add (as for the apex or anterior zone of the gland) further targeted cores., (© 2024 Wiley Periodicals LLC.)

Purpose: Prostatic urethral lift has been an effective ejaculation sparing treatment for benign prostatic hypertrophy. The aim of this study was to evaluate the effect on male semen parameters., Methods: Between July 2014 and January 2022, 20 young men with urinary symptoms of BPH, unresponsive to drug treatment and motivated to preserve ejaculation for eventual paternity, underwent UroLift. Semen analysis was performed before and 6 month after surgery with evaluation of pH, volume, sperm concentration, total motility, vitality and morphology according to WHO 2011. All underwent digital rectal examination, transrectal prostate ultrasound to measure prostate volume, PSA, uroflowmetry, cystoscopy and urodynamics test if necessary. Objective and subjective urinary function was scheduled at 1, 3, 6, 12 month than yearly with UFM, IPSS, IIEF-5, and MSHQ-EjD-SF., Results: At a mean follow-up of 36 month (range 12 to 63), no retroejaculation or changes in seminal parameters occurred. Mean age was 44.5 (range 36.5 to 48) years. Mean operative time was 15 (range 10 to 20) min and 2.5 (range 2 to 4) implants per patients were used. At 6 month there were no difference in terms of total sperm count, volume, pH, motility, vitality, morphology, liquefaction, leucocytes (p = 0.9; p = 0.8; p = 0.7; p = 1; p = 1; p = 1; p = 0,2; p = 0.5). At last, Q-max increased by 64.4% (p = 0.001), post-void residual volume decreased by 66.6% (p = 0.016), and IPSS decreased by 60% (p < 0.001). IIEF and MSHQ-EjD-SF were preserved (p = 0.14, p = 0.4)., Conclusions: UroLift appears safe technique to correct LUTS from BPH in young men desirous to preserve seminal analysis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Bladder cancer (BCa) represents the second most common malignancy of the genitourinary tract. The major risk factors include age, gender, smoking attitude, and occupational exposure, while the exact etiopathogenesis is still uncertain. Patients diagnosed with a BCa showing invasion of the muscle layer below the submucosa must undergo radical cystectomy (RC) with urinary diversion (UD). Many different surgical approaches to UD have been developed. Packaging an orthotopic neobladder (ON) with a bowel tract represents the gold standard when certain patient selection criteria are satisfied. Using PRISMA guidelines, we performed a systematic review assessing early (within 90 days) and late (beyond 90 days) post-procedural complications of different ON surgical approaches. A comprehensive systematic search was conducted in PubMed, Scopus, and Google Scholar databases to identify papers starting from 2012 using dedicated keywords ("neobladder", "orthotopic neobladder", "complications'' and "outcomes"). A total of 27 articles were found to satisfy the inclusion criteria and selected. Although the ON is a safe procedure that guarantees the patient the best quality of life (QoL), it is not free from risks. Many complications could occur during and after the surgical time which imposes the necessity of strict follow-up and careful checks over time, which should be properly discussed with patients before., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: This study aimed to examine current global practices in regenerative therapy (RT) for erectile dysfunction (ED) and to establish expert recommendations for its use, addressing the current lack of solid evidence and standardized guidelines., Materials and Methods: A 39-question survey was developed by senior Global Andrology Forum (GAF) experts to comprehensively cover clinical aspects of RT. This was distributed globally via a secure online Google Form to ED specialists through the GAF website, international professional societies, and social media, the responses were analyzed and presented for frequencies as percentages. Consensus on expert recommendations for RT use was achieved using the Delphi method., Results: Out of 479 respondents from 62 countries, a third reported using RT for ED. The most popular treatment was low-intensity shock wave therapy (54.6%), followed by platelet-rich plasma (24.5%) and their combination (14.7%), with stem cell therapy being the least used (3.7%). The primary indication for RT was the refractory or adverse effects of PDE5 inhibitors, with the best effectiveness reported in middle-aged and mild-to-moderate ED patients. Respondents were confident about its overall safety, with a significant number expressing interest in RT's future use, despite pending guidelines support., Conclusions: This inaugural global survey reveals a growing use of RT in ED treatment, showcasing its diverse clinical applications and potential for future widespread adoption. However, the lack of comprehensive evidence and clear guidelines requires further research to standardize RT practices in ED treatment., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Background : Programmed death-ligand 1 (PD-L1) expression has been recognized as a potential biomarker for various cancers, yet its diagnostic and prognostic significance in urothelial bladder cancer (BCa) requires further investigation. Methods : In this prospective single-center study, we aimed to assess the feasibility and diagnostic adequacy of PD-L1 expression analysis using cytoinclusion in BCa patients. We enrolled consecutive patients undergoing endoscopic transurethral resection of bladder tumor (TURBT), repeat TURBT, or robot-assisted radical cystectomy. Urinary and tissue specimens were collected from these patients for cytoinclusion and histopathological analysis to evaluate PD-L1 expression. Results : Out of 29 patients, PD-L1 expression was detected from cytoinclusion in 42.8% (3 out of 7), 10% (1 out of 10), and 66.8% (8 out of 12) of patients with negative/papilloma, low-grade, and high-grade tumors, respectively. Conversely, histopathological analysis identified PD-L1 expression in 57.2% (4 out of 7), 30% (3 out of 10), and 83.3% (10 out of 12) of patients with negative/papilloma, low-grade, and high-grade tumors, respectively. The diagnostic concordance between cytoinclusion and histopathology was 85.7%, 80%, and 83.3% in patients with negative/papilloma, low-grade, and high-grade tumors, respectively. Conclusions : Our study underscores the promise of cytoinclusion as a minimally invasive method for quantifying urinary PD-L1 percentages. This approach could serve as both a potential prognostic and diagnostic indicator, easily obtainable from urine samples. Standardizing this technique could facilitate its widespread use as a valuable tool.

Previous published studies have shown an improvement of penile hemodynamic parameters after low-intensity extracorporeal shockwave therapy (Li-ESWT). However, the clinical significance of these findings remains unclear, and definitive selection criteria for Li-ESWT based on preexisting comorbidities have yet to be established. This was an observational study of 113 patients with ED, evaluated between January 2019 and December 2021 in Andrology Unit at the Department of Urology and Renal Transplantation, University of Foggia (Foggia, Italy). Penile dynamic Doppler was performed to evaluate vascular parameters and 5-item version of the International Index of Erectile Dysfunction (IIEF-5) questionnaire was administered to assess the severity of ED. This was repeated 1 month after treatment. Patients with a peak systolic velocity (PSV) <30 cm s -1 were considered eligible for Li-ESWT. Our protocol consisted of 8 weekly sessions with 1500 strokes distributed in 5 different locations along the penis. After treatment, a significant mean (±standard deviation [s.d.]) PSV increase of 5.0 (±3.4) cm s -1 was recorded and 52/113 (46.0%) patients reached a PSV >30 cm s -1 at posttherapeutic penile dynamic Doppler. A clinically significant IIEF-5 score improvement was observed in 7 patients, 21 patients, and 2 patients with mild-to-moderate, moderate, and severe pretreatment ED, respectively. No different outcomes were assessed based on smoking habits, previous pelvic surgery, or use of oral phosphodiesterase-5 inhibitor (PDE5i). On the other side, only 1 (6.7%) in 15 patients with diabetes mellitus showed an IIEF-5 score improvement after Li-ESWT. Shockwave treatment determined a significant increase in PSV and correlated IIEF-5 improvement in ED patients. This advantage seemed particularly evident for moderate ED and was not affected by smoking habits, previous pelvic surgery, and use of PDE5i. Conversely, diabetic patients did not benefit from the treatment., (Copyright © 2024 Copyright: ©The Author(s)(2024).)

Background: The relationship between venous thromboembolism (VTE) and solid malignancy has been established over the decades. With rising projected rates of bladder cancer (BCa) worldwide as well as increasing number of patients experiencing BCa and VTE, our aim is to assess the impact of a preoperative VTE diagnosis on perioperative outcomes and health-care costs in BCa cases undergoing radical cystectomy (RC)., Methods: Patients ≥18 years of age with BCa diagnosis and undergoing open or minimally invasive (MIS) RC were identified in the Merative™ Marketscan ® Research Databases between 2007 and 2021. The association of previous VTE history with 90-day complication rates, postoperative VTE events, rehospitalization, and total hospital costs (2021 USA dollars) was determined by multivariable logistic regression modeling adjusted for patient and perioperative confounders. Sensitivity analysis on VTE degree of severity (i.e., pulmonary embolism [PE] and/or peripheral deep venous thrombosis [DVT]) was also examined., Results: Out of 8759 RC procedures, 743 (8.48%) had a previous positive history for any VTE including 245 (32.97%) PE, 339 (45.63%) DVT and 159 (21.40%) superficial VTE. Overall, history of VTE before RC was strongly associated with almost any worse postoperative outcomes including higher risk for any and apparatus-specific 90-days postoperative complications (odds ratio [OR]: 1.21, 95% CI, 1.02-1.44). Subsequent incidence of new VTE events (OR: 7.02, 95% CI: 5.93-8.31), rehospitalization (OR: 1.25, 95% CI: 1.06-1.48), other than home/self-care discharge status (OR: 1.53, 95% CI: 1.28-1.82), and higher health-care costs related to the RC procedure (OR: 1.43, 95% CI: 1.22-1.68) were significantly associated with a history of VTE., Conclusions: Preoperative VTE in patients undergoing RC significantly increases morbidity, post-procedure VTE events, hospital length of stay, rehospitalizations, and increased hospital costs. These findings may help during the BCa counseling on risks of surgery and hopefully improve our ability to mitigate such risks.

Oxidative stress is one of the main mechanisms responsible for male infertility. Various conditions such as varicocele, obesity, advanced age, and lifestyle can lead to an increase in reactive oxygen species, causing an oxidative imbalance in the reproductive environment. Spermatozoa are sensitive to reactive oxygen species and require energy to carry out their main function of fertilizing the egg. Excessive reactive oxygen species can affect sperm metabolism, leading to immobility, impaired acrosome reaction, and cell death, thereby impairing reproductive success. This double-blind randomized study evaluated the effect of supplementation with L-carnitine, acetyl-L-carnitine, vitamins, and other nutrients on semen quality in 104 infertile patients with or without varicocele, while also investigating the impact of factors such as obesity and advanced age on treatment. Sperm concentration significantly increased in the supplemented group compared to the placebo group ( P = 0.0186). Total sperm count also significantly increased in the supplemented group ( P = 0.0117), as did sperm motility ( P = 0.0120). The treatment had a positive effect on patients up to 35 years of age in terms of sperm concentration ( P = 0.0352), while a body mass index (BMI) above 25 kg m -2 had a negative effect on sperm concentration ( P = 0.0110). Results were not showing a net benefit in stratifying patients in accordance with their BMI since sperm quality increase was not affected by this parameter. In conclusion, antioxidant supplementation may be beneficial for infertile patients and has a more positive effect on younger patients with a normal weight., (Copyright © 2024 Copyright: © The Author(s)(2024).)

Background: The surgical landscape for Lower Urinary Tract Symptoms (LUTS) and Benign Prostatic Hyperplasia (BPH) has evolved with the introduction of Minimally Invasive Surgical Therapies (MISTs), recognizing the impact of sexual function on patients' well-being, and prioritizing ejaculation-sparing approaches., Methods: This systematic review explored ejaculation sparing after classic endoscopic procedures and MISTs (iTind, Rezūm, Urolift, Aquablation, and TPLA) and a literature search yielded 41 studies., Results: While all procedures demonstrated efficacy in improving LUTS/BPH symptoms (IPSS, QoL, Qmax), a subset of studies evaluated ejaculatory function. Positive outcomes were noted, challenging the historical association of BPH surgeries with ejaculatory dysfunction. Variations in study design, patient cohorts, and limited long-term data present challenges. Notably, the lack of baseline specificity, use of alpha-blockers, and non-specific sexual function assessments underscore potential biases., Conclusions: Despite limitations, the review tentatively concluded that MISTs, including iTind, Rezūm, Urolift, Aquablation, and TPLA, appear comparable in sparing ejaculation. Long-term studies are essential to validate sustainability, and comparative research should assess trade-offs between MISTs and traditional surgeries. Incorporating patient-reported outcomes and quality of life assessments will enhance future investigations, refining MISTs as standard therapeutic options for LUTS/BPH., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Bladder cancer (BC) is one of the most prevalent cancers worldwide. Non-muscle invasive bladder cancer (NMIBC), comprising the majority of initial BC presentations, requires accurate risk stratification for optimal management. This review explores the evolving role of programmed cell death ligand 1 (PD-L1) as a prognostic biomarker in NMIBC, with a particular focus on its implications in the context of Bacillus Calmette-Guérin (BCG) immunotherapy. The literature suggests a potential association between elevated PD-L1 status and adverse outcomes, resistance to BCG treatment, and disease progression. However, conflicting findings and methodological issues highlight the heterogeneity of PD-L1 assessment in NMIBC, probably due to the complex biological mechanisms that regulate the interaction between PD-L1 and the tumor microenvironment. The identification of PD-L1 as a prognostic biomarker provides ground for tailored therapeutic interventions, including immune checkpoint inhibitors (ICIs). Nevertheless, challenges such as intratumoral heterogeneity and technical issues underscore the need for standardized protocols and larger, homogeneous trials. This review contributes to the ongoing debate on the personalized management of NMIBC patients, focusing on the advances and perspectives of incorporating PD-L1 as a biomarker in this setting.

Purpose: Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates contemporary global practices related to medical and surgical management for patients with NOA., Materials and Methods: A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process., Results: Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in <10% of men with Klinefelter syndrome and 41.3% routinely recommended preimplantation genetic testing. Varicocele repair prior to SSR is recommended by 57.7%. Half of the respondents (57.4%) reported using ultrasound to identify the most vascularized areas in the testis for SSR. One-third proceed directly to microdissection testicular sperm extraction (mTESE) in every case of NOA while others use a staged approach. After a failed conventional TESE, 23.8% wait for 3 months, while 33.1% wait for 6 months before proceeding to mTESE. The cut-off of follicle-stimulating hormone for positive SSR was reported to be 12-19 IU/mL by 22.5% of participants and 20-40 IU/mL by 27.8%, while 31.8% reported no upper limit., Conclusions: This is the largest survey to date on the real-world medical and surgical management of NOA by reproductive experts. It demonstrates a diverse practice pattern and highlights the need for evidence-based international consensus guidelines., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Introduction: Upper tract urothelial carcinoma is rare but has a poor prognosis. Prognostic factors have been extensively studied in order to provide the best possible management for patients. We have aimed to investigate commonly available factors predictive of recurrence and survival in this patient population at high risk of death and recurrence, with an emphasis on the effects of age (using a cutoff of 70 years) on survival outcomes., Patients and Methods: From 1387 patients with clinically nonmetastatic upper tract urothelial carcinoma treated with radical nephroureterectomy at 21 academic hospital centers between 2005 and 2021, 776 patients were eligible and included in the study. Univariable and multivariable Cox regression models were built to evaluate the independent prognosticators for intravesical and extravesical recurrence, overall survival, and cancer-specific survival according to age groups. A P value of <.05 was considered statistically significant., Results: We did not find an association between groups aged <70 and >70 years old and preoperatively clinical or histopathological characteristics. Kaplan-Meier analysis was found no statistical significance between the 2 age groups in terms of intravesical or extravesical recurrence (P = .09 and P = .57). Overall survival (P = .0001) and cancer-specific survival (P = .0001) have been found to be statistically significantly associated with age as independent predictors (confounding factors: gender, tumor size, tumor side, clinical T stage, localization, preoperative hydronephrosis, tumor localization, type of surgery, multifocality of the tumor, pathological grade, lymphovascular invasion, concomitant CIS, lymph node status, necrosis, or history of previous bladder cancer)., Conclusion: This research confirms that patients aged 70 and above who undergo radical nephroureterectomy may have worse outcomes compared to younger patients, older patients needing an improved care and management of UTUC to improve their outcomes in the setting of an increase in this aged population group., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Renal cell carcinoma (RCC) remains a formidable diagnostic challenge, especially in the context of small renal masses. The quest for non-invasive screening tools and biomarkers has steered research towards liquid biopsy, focusing on microRNAs (miRNAs), exosomes, and circulating tumor cells (CTCs). MiRNAs, small non-coding RNAs, exhibit notable dysregulation in RCC, offering promising avenues for diagnosis and prognosis. Studies underscore their potential across various biofluids, including plasma, serum, and urine, for RCC detection and subtype characterization. Encouraging miRNA signatures show correlations with overall survival, indicative of their future relevance in RCC management. Exosomes, with their diverse molecular cargo, including miRNAs, emerge as enticing biomarkers, while CTCs, emanating from primary tumors into the bloodstream, provide valuable insights into cancer progression. Despite these advancements, clinical translation necessitates further validation and standardization, encompassing larger-scale studies and robust evidence generation. Currently lacking approved diagnostic assays for renal cancer, the potential future applications of liquid biopsy in follow-up care, treatment selection, and outcome prediction in RCC patients are profound. This review aims to discuss and highlight recent advancements in liquid biopsy for RCC, exploring their strengths and weaknesses in the comprehensive management of this disease.

Background: The use of the new thulium fiber laser in enucleation of the prostate (ThuFLEP) has been introduced recently., Objective: To evaluate complications and urinary incontinence (UI) after ThuFLEP in small and large prostate volume (PV)., Design Setting and Participants: We retrospectively reviewed patients who underwent ThuFLEP in six centers (from January 2020 to January 2023). The exclusion criteria were concomitant lower urinary tract surgery, previous prostate/urethral surgery, prostate cancer, and pelvic radiotherapy., Outcome Measurements and Statistical Analysis: Patients were divided into two groups: group 1: PV ≤80 ml; group 2: PV >80 ml. Univariable and multivariable logistic regression analyses were performed to evaluate the independent predictors of overall UI., Results and Limitations: There were 1458 patients in group 1 and 1274 in group 2. There was no significant difference in age. The median PV was 60 (61-72) ml in group 1 and 100 (90-122) ml in group 2. En bloc enucleation was employed more in group 1, while the early apical release technique was used more in group 2. The rate of prolonged irrigation for hematuria, urinary tract infection, and acute urinary retention did not differ significantly. Blood transfusion rate was significantly higher in group 2 (0.5% vs 2.0%, p  = 0.001). There was no significant difference in the overall UI rate (12.3% in group 1 vs 14.7% in group 2, p  = 0.08). A multivariable regression analysis showed that preoperative postvoiding urine residual (odds ratio 1.004, 95% confidence interval 1.002-1.007, p  < 0.01) was the only factor significantly associated with higher odds of UI. A limitation of this study was its retrospective nature., Conclusions: Complications and UI rates following ThuFLEP were similar in patients with a PV up to or larger than 80 ml except for the blood transfusion rate that was higher in the latter., Patient Summary: In this study, we looked at outcomes after thulium fiber laser in enucleation of the prostate stratified by PV. We found that blood transfusion was higher in men with PV >80 ml, but urinary incontinence was similar., (© 2024 The Author(s).)

Purpose: To evaluate complications and urinary incontinence (UI) after endoscopic enucleation of the prostate (EEP) stratified by prostate volume (PV)., Methods: We retrospectively reviewed patients with benign prostatic hyperplasia who underwent EEP with different energy sources in 14 centers (January 2019-January 2023)., Inclusion Criteria: prostate volume ≥ 80 ml., Exclusion Criteria: prostate cancer, previous prostate/urethral surgery, pelvic radiotherapy., Primary Outcome: complication rate., Secondary Outcomes: incidence of and factors affecting postoperative UI. Patients were divided into 3 groups. Group 1: PV = 80-100 ml; Group 2 PV = 101-200 ml; Group 3 PV > 200 ml. Multivariable logistic regression analysis was performed to evaluate independent predictors of overall incontinence., Results: There were 486 patients in Group 1, 1830 in Group 2, and 196 in Group 3. The most commonly used energy was high-power Holmium laser followed by Thulium fiber laser in all groups. Enucleation, morcellation, and total surgical time were significantly longer in Group 2. There was no significant difference in overall 30-day complications and readmission rates. Incontinence incidence was similar (12.1% in Group 1 vs. 13.2% in Group 2 vs. 11.7% in Group 3, p = 0.72). The rate of stress and mixed incontinence was higher in Group 1. Multivariable regression analysis showed that age (OR 1.019 95% CI 1.003-1.035) was the only factor significantly associated with higher odds of incontinence., Conclusions: PV has no influence on complication and UI rates following EEP. Age is risk factor of postoperative UI., (© 2024. The Author(s).)

There is an ongoing need for biomarkers that could reliably predict the outcome of BC and that could guide the management of this disease. In this setting, we aimed to explore the prognostic value of the transcription factor P63 in patients with muscle-invasive bladder cancer (MIBC) having undergone radical cystectomy. The correlation between P63 expression and clinicopathological features (tumor stage, nodes involvement, patterns of muscularis propria invasion, papillary architecture, anaplasia, concomitant carcinoma in situ, lymphovascular invasion, perineural invasion, necrosis) and molecular subtyping (basal and luminal type tumors) was tested in 65 radical cystectomy specimens and matched with cancer-specific survival (CSS) and overall survival (OS). P63-negative tumors displayed significantly higher rates of pattern 2 of muscularis propria invasion (50% vs. 14%, p = 0.002) and variant histology (45% vs. 19%, p = 0.022) compared to P63-positive ones. According to the combined expression of CK5/6 and CK20 (Algorithm #1), P63-positive and P63-negative tumors were mostly basal-like and double-negative, respectively ( p = 0.004). Using Algorithm #2, based on the combined expression of CK5/6 and GATA3, the vast majority of tumors were luminal overall and in each group ( p = 0.003). There was no significant difference in CSS and OS between P63-positive and P63-negative tumors, but the former featured a trend towards longer OS. Though associated with pathological features harboring negative prognostic potential, P63 status as such failed to predict CSS and OS. That said, it may contribute to better molecular subtyping of MIBC.

Background: In patients affected by high-risk nonmuscle invasive bladder cancer (HR-NMIBC) progression to muscle invasive status is considered as the main indicator of local treatment failure. We aimed to investigate the effect of progression and time to progression on overall survival (OS) and to investigate their validity as surrogate endpoints., Methods: A total of 1,510 patients from 18 different institutions treated for T1 high grade NMIBC, followed by a secondary transurethral resection and BCG intravesical instillation. We relied on random survival forest (RSF) to rank covariates based on OS prediction. Cox's regression models were used to quantify the effect of covariates on mortality., Results: During a median follow-up of 49.0 months, 485 (32.1%) patients progressed to MIBC, while 163 (10.8%) patients died. The median time to progression was 82 (95%CI: 78.0-93.0) months. In RSF time-to-progression and age were the most predictive covariates of OS. The survival tree defined 5 groups of risk. In multivariable Cox's regression models accounting for progression status as time-dependent covariate, shorter time to progression (as continuous covariate) was associated with longer OS (HR: 9.0, 95%CI: 3.0-6.7; P < 0.001). Virtually same results after time to progression stratification (time to progression ≥10.5 months as reference)., Conclusion: Time to progression is the main predictor of OS in patients with high risk NMIBC treated with BCG and might be considered a coprimary endpoint. In addition, models including time to progression could be considered for patients' stratification in clinical practice and at the time of clinical trials design., Competing Interests: Declaration of competing interest Each of the authors certify that the manuscript represents original and valid work that has not been previously published and is not currently under consideration by any other journal. Additionally, all the authors: have given final approval of the submitted manuscript approved the contents of this paper and have participated sufficiently in the work to take public responsibility for all content. None of the contributing authors have any conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript. No funding or other financial support was received., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Abstract: The increasing importance of treatment of lower urinary tract symptoms (LUTS), while avoiding side effects and maintaining sexual function, has allowed for the development of minimally invasive surgical therapies (MISTs). Recently, the European Association of Urology guidelines reported a paradigm shift from the management of benign prostatic hyperplasia (BPH) to the management of nonneurogenic male LUTS. The aim of the present review was to evaluate the efficacy and safety of the most commonly used MISTs: ablative techniques such as aquablation, prostatic artery embolization, water vapor energy, and transperineal prostate laser ablation, and nonablative techniques such as prostatic urethral lift and temporarily implanted nitinol device (iTIND). MISTs are becoming a new promise, even if clinical trials with longer follow-up are still lacking. Most of them are still under investigation and, to date, only a few options have been given as a recommendation for use. They cannot be considered as standard of care and are not suitable for all patients. Advantages and disadvantages should be underlined, without forgetting our objective: treatment of LUTS and re-treatment avoidance., (Copyright © 2023 Copyright: © The Author(s)(2023).)

Purpose: The purpose of this meta-analysis is to study the impact of varicocele repair in the largest cohort of infertile males with clinical varicocele by including all available studies, with no language restrictions, comparing intra-person conventional semen parameters before and after the repair of varicoceles., Materials and Methods: The meta-analysis was performed according to PRISMA-P and MOOSE guidelines. A systematic search was performed in Scopus, PubMed, Cochrane, and Embase databases. Eligible studies were selected according to the PICOS model (Population: infertile male patients with clinical varicocele; Intervention: varicocele repair; Comparison: intra-person before-after varicocele repair; Outcome: conventional semen parameters; Study type: randomized controlled trials [RCTs], observational and case-control studies)., Results: Out of 1,632 screened abstracts, 351 articles (23 RCTs, 292 observational, and 36 case-control studies) were included in the quantitative analysis. The before-and-after analysis showed significant improvements in all semen parameters after varicocele repair (except sperm vitality); semen volume: standardized mean difference (SMD) 0.203, 95% CI: 0.129-0.278; p<0.001; I²=83.62%, Egger's p=0.3329; sperm concentration: SMD 1.590, 95% CI: 1.474-1.706; p<0.001; I²=97.86%, Egger's p<0.0001; total sperm count: SMD 1.824, 95% CI: 1.526-2.121; p<0.001; I²=97.88%, Egger's p=0.0063; total motile sperm count: SMD 1.643, 95% CI: 1.318-1.968; p<0.001; I²=98.65%, Egger's p=0.0003; progressive sperm motility: SMD 1.845, 95% CI: 1.537%-2.153%; p<0.001; I²=98.97%, Egger's p<0.0001; total sperm motility: SMD 1.613, 95% CI 1.467%-1.759%; p<0.001; l2=97.98%, Egger's p<0.001; sperm morphology: SMD 1.066, 95% CI 0.992%-1.211%; p<0.001; I²=97.87%, Egger's p=0.1864., Conclusions: The current meta-analysis is the largest to date using paired analysis on varicocele patients. In the current meta-analysis, almost all conventional semen parameters improved significantly following varicocele repair in infertile patients with clinical varicocele., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Purpose: Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to the use of SDF assays and investigate the barriers and limitations that clinicians face in incorporating these tests into their practice., Materials and Methods: Clinicians managing male infertility were invited to complete an online survey on practices related to SDF diagnostic and treatment approaches. Their responses related to the technical aspects of SDF testing, current professional society guidelines, and the literature were used to generate expert recommendations via the Delphi method. Finally, challenges related to SDF that the clinicians encounter in their daily practice were captured., Results: The survey was completed by 436 reproductive clinicians. Overall, terminal deoxynucleotidyl transferase deoxyuridine triphosphate Nick-End Labeling (TUNEL) is the most commonly used assay chosen by 28.6%, followed by the sperm chromatin structure assay (24.1%), and the sperm chromatin dispersion (19.1%). The choice of the assay was largely influenced by availability (70% of respondents). A threshold of 30% was the most selected cut-off value for elevated SDF by 33.7% of clinicians. Of respondents, 53.6% recommend SDF testing after 3 to 5 days of abstinence. Although 75.3% believe SDF testing can provide an explanation for many unknown causes of infertility, the main limiting factors selected by respondents are a lack of professional society guideline recommendations (62.7%) and an absence of globally accepted references for SDF interpretation (50.3%)., Conclusions: This study represents the largest global survey on the technical aspects of SDF testing as well as the barriers encountered by clinicians. Unified global recommendations regarding clinician implementation and standard laboratory interpretation of SDF testing are crucial., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Background: Peyronie's disease affects up to 9% of men and is often accompanied by pain and/or erectile dysfunction. It is characterized by an inflammatory process that is the grassroots of the subsequent fibrosis stage. There is an unmet need to evaluate its onset and progression. Among the newly proposed biomarkers of inflammation, authors developed a novel systemic immune-inflammation index (SII) based on lymphocyte, neutrophil, and platelet counts. Similarly, a recent study reported that a neutrophil-to-eosinophil ratio (NER) represents systemic inflammation., Results: A 49-patient group with Peyronie's disease as confronted with 50 well-matched for age and BMI controls. As laboratory evaluation of inflammation, SII, NER and the eosinophil to neutrophil ratio (ENR) were studied. As a likely risk factor for the presence of Peyronie's disease, a higher prevalence of hypercholesterolemia, hyperglycemia and hypertension was discovered in the patients compared to controls. A significant difference was found in the median values of the NER between the two selected groups, i.e., 32.5 versus 17.3 (p = 0.0021). As expected, also ENR was significantly different. The receiver operating characteristic curves for SII, ENR and NER were 0.55, 0.32 and 0.67, respectively, highlighting the best performance of NER. The cut-off for NER was 12.1, according to the Youden test., Conclusions: According to our results, any evaluation of circulating eosinophil, evaluated as NER, beyond being a signature of immuno-inflammatory response, help assess tissue homeostasis, since eosinophils are now considered multifunctional leukocytes and give a picture of the inflammatory process and repair process belonging to Peyronie's disease., (© 2023. The Author(s).)

Introduction: Inflatable penile prosthesis are the definitive treatment for erectile dysfunction. The two most used surgical approaches to position the implants are the penoscrotal and the infrapubic. Current trends showed that the penoscrotal approach is extensively preferred however, there is not conclusive evidence demonstrating the superiority of one technique over the other. The aim of this review is to summarize the scientific evidence available and to underline strengths and weaknesses of the two techniques., Evidence Acquisition: We conducted a comprehensive search of MEDLINE, Cochrane Library, and National Center for Biotechnology Information PubMed to identify relevant published articles. The included studies had to explicitly examine the use of three-piece inflatable penile prosthesis with a focus on the surgical access method and complications., Evidence Synthesis: Twenty-six articles were included in the review: seven narrative reviews, five retrospective observational studies, five prospective observational studies, and nine mixed methodology studies. The most frequent approach was the penoscrotal, which was also found more comfortable (RG1) by the operators in one study. The infrapubic approach lasts less and one study demonstrated higher satisfaction by the patients., Conclusions: There is no evidence of significant differences in complications among the penoscrotal and infrapubic approaches. While the infrapubic approach is faster and patients were more satisfied, the penoscrotal approach is the most used by far. This is likely related to the more straightforward procedure through this access and the excellent surgical field exposure. For these reasons, it is also preferred in the most complex cases.

Purpose: The primary aim of this study was to evaluate if exposure to 5-alpha-reductase inhibitors (5-ARIs) modifies the effect of MRI for the diagnosis of clinically significant Prostate Cancer (csPCa) (ISUP Gleason grade ≥ 2)., Methods: This study is a multicenter cohort study including patients undergoing prostate biopsy and MRI at 24 institutions between 2013 and 2022. Multivariable analysis predicting csPCa with an interaction term between 5-ARIs and PIRADS score was performed. Sensitivity, specificity, and negative (NPV) and positive (PPV) predictive values of MRI were compared in treated and untreated patients., Results: 705 patients (9%) were treated with 5-ARIs [median age 69 years, Interquartile range (IQR): 65, 73; median PSA 6.3 ng/ml, IQR 4.0, 9.0; median prostate volume 53 ml, IQR 40, 72] and 6913 were 5-ARIs naïve (age 66 years, IQR 60, 71; PSA 6.5 ng/ml, IQR 4.8, 9.0; prostate volume 50 ml, IQR 37, 65). MRI showed PIRADS 1-2, 3, 4, and 5 lesions in 141 (20%), 158 (22%), 258 (37%), and 148 (21%) patients treated with 5-ARIs, and 878 (13%), 1764 (25%), 2948 (43%), and 1323 (19%) of untreated patients (p < 0.0001). No difference was found in csPCa detection rates, but diagnosis of high-grade PCa (ISUP GG ≥ 3) was higher in treated patients (23% vs 19%, p = 0.013). We did not find any evidence of interaction between PIRADS score and 5-ARIs exposure in predicting csPCa. Sensitivity, specificity, PPV, and NPV of PIRADS ≥ 3 were 94%, 29%, 46%, and 88% in treated patients and 96%, 18%, 43%, and 88% in untreated patients, respectively., Conclusions: Exposure to 5-ARIs does not affect the association of PIRADS score with csPCa. Higher rates of high-grade PCa were detected in treated patients, but most were clearly visible on MRI as PIRADS 4 and 5 lesions., Trial Registration: The present study was registered at ClinicalTrials.gov number: NCT05078359., (© 2023. The Author(s).)

Bladder cancer (BCa) is a common type of cancer that affects the urinary bladder. The early detection and management of BCa is critical for successful treatment and patient outcomes. In recent years, researchers have been exploring the use of biomarkers as a non-invasive and effective tool for the detection and monitoring of BCa. One such biomarker is programmed death-ligand 1 (PD-L1), which is expressed on the surface of cancer cells and plays a crucial role in the evasion of the immune system. Studies have shown that the PD-L1 expression is higher in BCa tumors than in healthy bladder tissue. Additionally, PD-L1 expression might even be detected in urine samples in BCa patients, in addition to the examination of a histological sample. The technique is being standardized and optimized. We reported how BCa patients had higher urinary PD-L1 levels than controls by considering BCa tumors expressing PD-L1 in the tissue specimen. The expression of PD-L1 in urinary BCa cells might represent both a diagnostic and a prognostic tool, with the perspective that the PD-L1 expression of exfoliate urinary cells might reveal and anticipate eventual BCa recurrence or progression. Further prospective and longitudinal studies are needed to assess the expression of PD-L1 as a biomarker for the monitoring of BCa patients. The use of PD-L1 as a biomarker for the detection and monitoring of BCa has the potential to significantly improve patient outcomes by allowing for earlier detection and more effective management of the disease.

Purpose: Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recommendations for managing this condition., Materials and Methods: An online global survey on clinical practices related to SDF was disseminated to reproductive clinicians, according to the CHERRIES checklist criteria. Management protocols for various conditions associated with SDF were captured and compared to the relevant recommendations in professional society guidelines and the appropriate available evidence. Expert recommendations and consensus on the management of infertile men with elevated SDF were then formulated and adapted using the Delphi method., Results: A total of 436 experts from 55 different countries submitted responses. As an initial approach, 79.1% of reproductive experts recommend lifestyle modifications for infertile men with elevated SDF, and 76.9% prescribe empiric antioxidants. Regarding antioxidant duration, 39.3% recommend 4-6 months and 38.1% recommend 3 months. For men with unexplained or idiopathic infertility, and couples experiencing recurrent miscarriages associated with elevated SDF, most respondents refer to ART 6 months after failure of conservative and empiric medical management. Infertile men with clinical varicocele, normal conventional semen parameters, and elevated SDF are offered varicocele repair immediately after diagnosis by 31.4%, and after failure of antioxidants and conservative measures by 40.9%. Sperm selection techniques and testicular sperm extraction are also management options for couples undergoing ART. For most questions, heterogenous practices were demonstrated., Conclusions: This paper presents the results of a large global survey on the management of infertile men with elevated SDF and reveals a lack of consensus among clinicians. Furthermore, it demonstrates the scarcity of professional society guidelines in this regard and attempts to highlight the relevant evidence. Expert recommendations are proposed to help guide clinicians., Competing Interests: The authors have nothing to disclose., (Copyright © 2023 Korean Society for Sexual Medicine and Andrology.)

Introduction: Several programmed death ligand-1 (PD1/L1) immune checkpoint inhibitors (ICIs) are approved in urothelial carcinoma (UC)., Patients and Methods: To address the need for predictors of the efficacy of ICIs in metastatic urothelial carcinoma (mUC), randomized controlled trials of PD1/L1 inhibitors alone or in combination with chemotherapy in this patient population were systematically reviewed, and differences in ICI-associated survival outcomes according to available baseline variables were quantitatively assessed., Results: The quantitative analysis included 6524 patients with mUC. No visceral metastatic site (HR 0.67; 95% CI, 0.76-0.90) and high PDL-1 expression (HR 0.74; 95% CI, 0.640.87) were significantly associated with a reduced risk of death., Conclusion: Treatment with an ICI-containing regimen was associated with a reduced risk of death in mUC patients, which was associated with PDL-1 expression and metastatic site. Further research is warranted., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The aim of this study was to validate externally a nomogram that relies on MRI volumetric parameters and clinical data to determine the need for a standard biopsy in addition to a target biopsy for men with suspicious prostate MRI findings. Methods: We conducted a retrospective analysis of a prospectively maintained database of 469 biopsy-naïve men who underwent prostate biopsies. These biopsies were guided by pre-biopsy multiparametric Magnetic Resonance Imaging (mpMRI) and were performed at two different institutions. We included men with a PIRADSsv 2.1 score from 3 to 5. Each patient underwent both an MRI-ultrasound fusion biopsy of identified MRI-suspicious lesions and a systematic biopsy according to our protocol. The lesion volume percentage was determined as the proportion of cancer volume on MRI relative to the entire prostate volume. The study's outcomes were iPCa (Gleason Grade Group 1) and csPCa (Gleason Grade Group > 1). We evaluated the model's performance using AUC decision curve analyses and a systematic analysis of model-derived probability cut-offs in terms of the potential to avoid diagnosing iPCa and to accurately diagnose csPCa. Results: The nomogram includes age, PSA value, prostate volume, PIRADSsv 2.1 score, percentage of MRI-suspicious lesion volume, and lesion location. AUC was determined to be 0.73. By using various nomogram cut-off thresholds (ranging from 5% to 30%), it was observed that 19% to 58% of men could potentially avoid undergoing standard biopsies. In this scenario, the model might miss 0% to 10% of diagnosis of csPCa and could prevent identifying 6% to 31% of iPCa cases. These results are in line with findings from the multi-institutional external validation study based on the IMPROD trial (n = 122) and the MULTI-IMPROD trial (n = 262). According to DCA, the use of this nomogram led to an increased overall net clinical benefit when the threshold probability exceeded 10%. Conclusions: This study supports the potential value of a model relying on MRI volumetric measurements for selecting individuals with clinical suspicion of prostate cancer who would benefit from undergoing a standard biopsy in addition to a targeted biopsy.

Urinary tract infections represent a common and significant health concern worldwide. The high rate of recurrence and the increasing antibiotic resistance of uropathogens are further worsening the current scenario. Nevertheless, novel key ingredients such as D-mannose, chondroitin sulphate, hyaluronic acid, and N -acetylcysteine could represent an important alternative or adjuvant to the prevention and treatment strategies of urinary tract infections. Several studies have indeed evaluated the efficacy and the potential use of these compounds in urinary tract health. In this review, we aimed to summarize the characteristics, the role, and the application of the previously reported compounds, alone and in combination, in urinary tract health, focusing on their potential role in urinary tract infections.

Anti-VEGF (vascular endothelial growth factor) agents were associated with increased risk of several cardiovascular events, while one meta-analysis did not show any significantly increased risk of cardiotoxicity associated with the use of immune checkpoint inhibitors (ICIs). This meta-analysis of randomized-controlled trials (RCTs) was designed to compare cardiovascular toxicity of anti-VEGF agents plus ICI vs anti-VEGF agents without ICIs. A systematic search of the literature was conducted to include all full papers reporting about phase II and III randomized controlled trials (RCTs) conducted in patients with solid malignancies randomized to an anti-VEGF agent plus an ICI vs. an anti-VEGF agent without an ICI. Overall incidences of cardiovascular events were compared between these two treatment groups estimating the corresponding odds ratios. This analysis suggests that ICIs may increase the risk of cardiovascular toxicities associated with anti-VEGF therapies. Further research, including real world studies, is warranted., Competing Interests: Declaration of Competing Interest, (Copyright © 2023 Elsevier B.V. All rights reserved.)

Artificial intelligence is highly regarded as the most promising future technology that will have a great impact on healthcare across all specialties. Its subsets, machine learning, deep learning, and artificial neural networks, are able to automatically learn from massive amounts of data and can improve the prediction algorithms to enhance their performance. This area is still under development, but the latest evidence shows great potential in the diagnosis, prognosis, and treatment of urological diseases, including bladder cancer, which are currently using old prediction tools and historical nomograms. This review focuses on highly significant and comprehensive literature evidence of artificial intelligence in the management of bladder cancer and investigates the near introduction in clinical practice.

Purpose: Sperm DNA fragmentation (SDF) testing was recently added to the sixth edition of the World Health Organization laboratory manual for the examination and processing of human semen. Many conditions and risk factors have been associated with elevated SDF; therefore, it is important to identify the population of infertile men who might benefit from this test. The purpose of this study was to investigate global practices related to indications for SDF testing, compare the relevant professional society guideline recommendations, and provide expert recommendations., Materials and Methods: Clinicians managing male infertility were invited to take part in a global online survey on SDF clinical practices. This was conducted following the CHERRIES checklist criteria. The responses were compared to professional society guideline recommendations related to SDF and the appropriate available evidence. Expert recommendations on indications for SDF testing were then formulated, and the Delphi method was used to reach consensus., Results: The survey was completed by 436 experts from 55 countries. Almost 75% of respondents test for SDF in all or some men with unexplained or idiopathic infertility, 39% order it routinely in the work-up of recurrent pregnancy loss (RPL), and 62.2% investigate SDF in smokers. While 47% of reproductive urologists test SDF to support the decision for varicocele repair surgery when conventional semen parameters are normal, significantly fewer general urologists (23%; p=0.008) do the same. Nearly 70% would assess SDF before assisted reproductive technologies (ART), either always or for certain conditions. Recurrent ART failure is a common indication for SDF testing. Very few society recommendations were found regarding SDF testing., Conclusions: This article presents the largest global survey on the indications for SDF testing in infertile men, and demonstrates diverse practices. Furthermore, it highlights the paucity of professional society guideline recommendations. Expert recommendations are proposed to help guide clinicians., Competing Interests: The authors have nothing to disclose., (Copyright © 2023 Korean Society for Sexual Medicine and Andrology.)

Introduction: New potential biomarkers to pre-intervention identification of a clinically significant prostate cancer (csPCa) will prevent overdiagnosis and overtreatment and limit quality of life impairment of PCa patients., Areas Covered: We have developed a comprehensive review focusing our research on the increasing knowledge of the role of SelectMDX® in csPCa detection. Areas identified as clinically relevant are the ability of SelectMDX® to predict csPCa in active surveillance setting, its predictive ability when combined with multiparametric MRI and the role of SelectMDX® in the landscape of urinary biomarkers., Expert Opinion: Several PCa biomarkers have been developed either alone or in combination with clinical variables to improve csPCa detection. SelectMDX® score includes genomic markers, age, PSA, prostate volume, and digital rectal examination. Several studies have shown consistency in the ability to improve detection of csPCa, avoidance of unnecessary prostate biopsies, helpful in decision-making for clinical benefit of PCa patients with future well designed, and impactful studies.

Background and Objectives: The Reporting and Data System (RADS) have been used in the attempts to standardize the results of oncological scans in different scenarios, such as lymph nodes, adding configuration criteria to size determination. We analyze the predictive value of preoperative Node-RADS determination at imaging for pelvic lymph node (PLN) involvement in cases of prostate cancer (PC) considered for radical prostatectomy (RP) with extended lymph node dissection (eLND) and we compare it with validate predictive nomograms (MSKCC, Briganti and Gandaglia)., Methods: 150 patients with a histological diagnosis of PC (high risk or intermediate with an estimated risk for pN+ higher than 5% using the Briganti or 7% using the Gandaglia nomogram) submitted for RP with an ePLND from 2018 and 2021 were retrospectively examined. Node-RADS determination was performed in all cases using the preoperative magnetic resonance (MR), performed by a radiologist blinded for pathologic results and compared with the MSKCC, Briganti 2012, Gandaglia 2017 and Gandaglia 2019 nomograms., Results: PLN involvement at final pathology (pN+) was found in 36/150 (24.0%) of cases and the mean percentage of positive LNs in pN+ cases was 15.90 ± 13.40. The mean number of PLNs removed at RP was similar (p = 0.188) between pN0 (23.9 ± 8.0) and pN+ (25.3 ± 8.0) cases. Considering a Node RADS 4-5 positive and a Node RADS 1-2 negative, the PPV was 100% and the NPV was 79.6%. A Node RADS score 4-5 showed a lower sensitivity (0.167 versus 0.972, 1.000, 0.971, 0.960 respectively), a higher specificity (1.000 versus 0.079, 0.096, 0.138, 0.186 respectively) and a similar AUC (0.583 versus 0.591, 0.581, 0.574, 0.597 respectively) when compared to MSKCC, Briganti 2012, Gandaglia 2017 and Gandaglia 2019 nomograms., Conclusions: Our evaluation suggests that Node RADS score, combining configuration criteria to size determination could improve specificity in terms of pathologic PLN prediction but a very low sensitivity has been also described., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: Radical cystectomy (RC) is the standard treatment for high-risk non muscle-invasive bladder cancer (NMIBC) failing first BCG treatment. A second BCG course is an option for those patients who refuse RC or are not eligible for it, but its success rate is quite low. Aim of the present study was to determine whether the addition of intravesical electromotive drug administration of mytomicin-C (EMDA-MMC) improved the efficacy of second BCG course., Methods: Patients with high-risk NMIBC having failed first BCG treatment and having refused RC were offered a second BCG induction course either alone (group A) or combined with EMDA-MMC (group B). Recurrence-free survival (RFS), progression-free survival (PFS) and cancer-specific survival (CSS) were tested., Results: Of the 80 evaluable patients, 44 were in group A and 36 in group B; median follow-up was 38 months. RFS was significantly worse in group A whereas there was no difference in PFS and CSS between the two groups. Stratifying by disease stage, Ta patients receiving combined treatment had statistically better RFS and PFS survival than those receiving BCG only; this difference did not apply to T1 patients. Multivariable analysis confirmed that combined treatment was a significant predictor of recurrence and was close to predict progression. No tested variable was predictive of recurrence or progression in T1 tumours. Among those who underwent RC, CSS was 61.5% in those who had progression and 100% in those who remained with NMIBC., Conclusion: Combined treatment improved RFS and PFS only in patients with Ta disease., (© 2023. The Author(s).)

Purpose: To evaluate oncological outcomes of partial gland cryoablation (PGC) for localized prostate cancer (PCa) in a cohort of elderly patients who required an active treatment., Methods: Data from 110 consecutive patients treated with PGC for localized PCa were collected. All patients underwent the same standardized follow-up with serum-PSA level and digital rectal examination. Prostate MRI and eventual re-biopsy were performed at twelve months after cryotherapy or in case of suspicion of recurrence. Biochemical recurrence was defined according to Phoenix criteria (PSA nadir + 2 ng/ml). Kaplan-Meier curves and Multivariable Cox Regression analyses were used to predict disease progression, biochemical recurrence- (BCS) and additional treatment-free survival (TFS)., Results: Median age was 75 years (IQR 70-79). PGC was performed in 54 (49.1%) patients with low-risk PCa, 42 (38.1%) with intermediate risk and 14 (12.8%) high risk. At a median follow-up of 36 months, we recorded a BCS and TFS of 75 and 81%, respectively. At 5 years, BCS was 68.5% and CRS 71.5%. High-risk prostate cancer was associated with lower TFS and BCS curves when compared with low-risk group (all p values < .03). A PSA reduction < 50% between preoperative level and nadir resulted as an independent failure predictor for all outcomes evaluated (all p values < .01). Age was not associated with worse outcomes., Conclusions: PGC could be a valid treatment for low- to intermediate PCa in elderly patients, when a curative approach is suitable in terms of life expectancy and quality of life., (© 2023. The Author(s).)

Radiomics and artificial intelligence (AI) may increase the differentiation of benign from malignant kidney lesions, differentiation of angiomyolipoma (AML) from renal cell carcinoma (RCC), differentiation of oncocytoma from RCC, differentiation of different subtypes of RCC, to predict Fuhrman grade, to predict gene mutation through molecular biomarkers and to predict treatment response in metastatic RCC undergoing immunotherapy. Neural networks analyze imaging data. Statistical, geometrical, textural features derived are giving quantitative data of contour, internal heterogeneity and gray zone features of lesions. A comprehensive literature review was performed, until July 2022. Studies investigating the diagnostic value of radiomics in differentiation of renal lesions, grade prediction, gene alterations, molecular biomarkers and ongoing clinical trials have been analyzed. The application of AI and radiomics could lead to improved sensitivity, specificity, accuracy in detecting and differentiating between renal lesions. Standardization of scanner protocols will improve preoperative differentiation between benign, low-risk cancers and clinically significant renal cancers and holds the premises to enhance the diagnostic ability of imaging tools to characterize renal lesions., 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.)

Introduction: Bacterial prostatitis (BP) is a common prostatic infection characterized by a bimodal distribution in young and older men, with a prevalence between 5-10% among all cases of prostatitis and a high impact on quality of life. Although the management of bacterial prostatitis involves the use of appropriate spectrum antibiotics, which represent the first choice of treatment, a multimodal approach encompassing antibiotics and nutraceutical products in order to improve the efficacy of chosen antimicrobial regimen is often required., Objective: To evaluate the efficacy of Flogofilm ® in association with fluoroquinolones in patients with chronic bacterial prostatitis (CBP)., Methods: Patients diagnosed with prostatitis (positivity to Meares-Stamey Test and symptoms duration > 3 months) at the University of Naples "Federico II", Italy, from July 2021 to December 2021, were included in this study. All patients underwent bacterial cultures and trans-rectal ultrasounds. Patients were randomized into two groups (A and B) receiving antibiotic alone or an association of antibiotics plus Flogofilm ® tablets containing Flogomicina ® for one month, respectively. The NIH-CPSI and IPSS questionnaires were administered at baseline, four weeks, twelve and twenty-four weeks., Results: A total of 96 (Group A = 47, Group B = 49) patients concluded the study protocol. The mean age was comparable, with a mean age of 34.62 ± 9.04 years for Group A and 35.29 ± 10.32 years for Group B ( p = 0.755), and IPSS at the baseline was 8.28 ± 6.33 and 9.88 ± 6.89 ( p = 0.256), respectively, while NIH-CPSI at baseline was 21.70 ± 4.38 and 21.67 ± 6.06 ( p = 0.959), respectively. At 1, 3 and 6 months, the IPSS score was 6.45 ± 4.8 versus 4.31 ± 4.35 ( p = 0.020), 5.32 ± 4.63 versus 3.20 ± 3.05 ( p = 0.042) and 4.91 ± 4.47 versus 2.63 ± 3.28 ( p = 0.005) for Groups A and B, respectively. Similarly, the NIH-CPSI total score at 1, 3 and 6 months was 16.15 ± 3.31 versus 13.10 ± 5.03 ( p < 0.0001), 13.47 ± 3.07 versus 9.65 ± 4.23 ( p < 0.0001) and 9.83 ± 2.53 versus 5.51 ± 2.84 ( p < 0.0001), respectively., Conclusions: Flogofilm ® , associated with fluoroquinolones, demonstrate a significant improvement in pain, urinary symptoms and quality of life in patients affected by chronic bacterial prostatitis in both IPSS and NIH-CPSI scores compared with fluoroquinolones alone.

Background: Recently, the European Association of Urology Guidelines Panel updated the prognostic factor risk groups model for non-muscle-invasive bladder cancer (NMIBC) with the introduction of a new group of patients at very high risk (VHR). Furthermore, three additional clinical risk factors (i.e., age>70 years, multiple papillary tumors; tumor diameter >3 cm) were proposed. However, the new scoring model was created by analyzing data from patients who did not receive BCG intravesical therapy., Methods: This is a retrospective multicenter study analyzing data of 920 patients with HGT1 NMIBC that underwent ReTUR e following BCG intravesical therapy. Patients were stratified into risk groups according to the 2021 new EAU NMIBC prognostic factor risk groups model. This study aimed to identify variables related to disease progression in a large cohort of HGT1 NMIBC patients who underwent both Re-TURB and BCG intravesical immunotherapy., Results: Median follow-up was 51 months (IQR 41-75), according to EAU NMIBC 2021 scoring model 179 (19.5%) patients were at VHR. Progression-free survival at 5 years was 68.2% and 59.9% for the whole sample and the VHR group, respectively. At multivariable regression model size >3 cm, multifocal tumor, concomitant CIS and LVI were identified as independently associated with disease progression., Conclusions: Although patients at VHR are more likely to experience disease progression during follow-up, the European Association of Urology (EAU) NMIBC 2021 scoring model appears to be suboptimal in patients who underwent ReTUR and intravesical BCG therapy.

Background: In an era of Bacillus of Calmette-Guérin (BCG) shortages, the comparative efficacy from different adjuvant intravesical BCG strains in non-muscle invasive bladder cancer (NMIBC) has not been clearly elucidated. We aim to compare, through a systematic review and meta-analysis, the cumulative BC recurrence rates and the best efficacy profile of worldwide available BCG strains over the last forty years., Methods: PubMed, Scopus, Web of Science, Embase, and Cochrane databases were searched from 1982 up to 2022. A meta-analysis of pooled BC recurrence rates was stratified for studies with ≤3-y vs. >3-y recurrence-free survival (RFS) endpoints and the strain of BCG. Sensitivity analysis, sub-group analysis, and meta-regression were implemented to investigate the contribution of moderators to heterogeneity. A random-effect network meta-analysis was performed to compare BCG strains on a multi-treatment level., Results: In total, n = 62 series with n = 15,412 patients in n = 100 study arms and n = 10 different BCG strains were reviewed. BCG Tokyo 172 exhibited the lowest pooled BC recurrence rate among studies with ≤3-y RFS (0.22 (95%CI 0.16-0.28). No clinically relevant difference was noted among strains at >3-y RFS outcomes. Sub-group and meta-regression analyses highlighted the influence of NMIBC risk-group classification and previous intravesical treated categories. Out of the n = 11 studies with n = 7 BCG strains included in the network, BCG RIVM, Tice, and Tokyo 172 presented with the best-predicted probability for efficacy, yet no single strain was significantly superior to another in preventing BC recurrence risk., Conclusion: We did not identify a BCG stain providing a clinically significant lower BC recurrence rate. While these findings might discourage investment in future head-to-head randomized comparison, we were, however, able to highlight some potential enhanced benefits from the genetically different BCG RIVM, Tice, and Tokyo 172. This evidence would support the use of such strains for future BCG trials in NMIBCs.

Background: Bladder cancer (BCa) is a heterogeneous disease with a variable prognosis and natural history. Cardiovascular disease (CVD), although completely different, has several similarities and possible interactions with cancer. The association between them is still unknown, but common risk factors between the two suggest a shared biology. Materials and Methods: This was a retrospective study that included patients who underwent transurethral resection of bladder tumor at two high-volume institutions. Depending on the presence of a previous history of CVD or not, patients were divided into two groups. Results: A total of 2050 patients were included, and 1638 (81.3%) were diagnosed with bladder cancer. Regarding comorbidities, the most common were hypertension (59.9%), cardiovascular disease (23.4%) and diabetes (22.4%). At univariate analysis, independent risk factors for bladder cancer were age and male sex, while protective factors were cessation of smoking and presence of CVD. All these results, except for ex-smoker status, were confirmed at the multivariate analysis. Another analysis was performed for patients with high-risk bladder cancer and, in this case, the role of CVD was not statistically significant. Conclusions: Our study pointed out a positive association between CVD and BCa incidence; CVD was an independent protective factor for BCa. This effect was not confirmed for high-risk tumors. Several biological and genomics mechanisms clearly contribute to the onset of both diseases, suggesting a possible shared disease pathway and highlighting the complex interplay of cancer and CVD. CVD treatment can involve different drugs with a possible effect on cancer incidence, but, to date, findings are still inconclusive.

Renal cancer management is challenging from diagnosis to treatment and follow-up. In cases of small renal masses and cystic lesions the differential diagnosis of benign or malignant tissues has potential pitfalls when imaging or even renal biopsy is applied. The recent artificial intelligence, imaging techniques, and genomics advancements have the ability to help clinicians set the stratification risk, treatment selection, follow-up strategy, and prognosis of the disease. The combination of radiomics features and genomics data has achieved good results but is currently limited by the retrospective design and the small number of patients included in clinical trials. The road ahead for radiogenomics is open to new, well-designed prospective studies, with large cohorts of patients required to validate previously obtained results and enter clinical practice.

Novel molecular imaging opportunities to preoperatively diagnose renal cell carcinoma is under development and will add more value in limiting the postoperative renal function loss and morbidity. We aimed to comprehensively review the research on single photon emission computed tomography/computed tomography (SPECT/CT) and positron emission tomography computed tomography (PET-CT) molecular imaging and to enhance the urologists' and radiologists' knowledge of the current research pattern. We identified an increase in prospective and also retrospective studies that researched to distinguish between benign and malignant lesions and between different clear cell renal cell carcinoma subtypes, with small numbers of patients studied, nonetheless with excellent results on specificity, sensitivity and accuracy, especially for 99m Tc-sestamibi SPECT/CT that delivers quick results compared to a long acquisition time for girentuximab PET-CT, which instead gives better image quality. Nuclear medicine has helped clinicians in evaluating primary and secondary lesions, and has lately returned with new and exciting insights with novel radiotracers to reinforce its diagnostic potential in renal carcinoma. To further limit the renal function loss and post-surgery morbidity, future research is mandatory to validate the results and to clinically implement the diagnostic techniques in the context of precision medicine.

Risk calculator (RC) combining PSA with other clinical information can help to better select patients at risk of prostate cancer (PCa) for prostate biopsy. The present study aimed to develop a new Pca RC, including MRI and bladder outlet obstruction parameters (BOOP). The ability of these parameters in predicting PCa and clinically significant PCa (csPCa: ISUP GG ≥ 2) was assessed by binary logistic regression. A total of 728 patients were included from two institutions. Of these, 395 (54.3%) had negative biopsies and 161 (22.11%) and 172 (23.6%) had a diagnosis of ISUP GG1 PCa and csPCa. The two RC ultimately included age, PSA, DRE, prostate volume (pVol), post-voided residual urinary volume (PVR), and PIRADS score. Regarding BOOP, higher prostate volumes (csPCa: OR 0.98, CI 0.97,0.99) and PVR ≥ 50 mL (csPCa: OR 0.27, CI 0.15, 0.47) were protective factors for the diagnosis of any PCa and csPCa. AUCs after internal validation were 0.78 (0.75, 0.82) and 0.82 (0.79, 0.86), respectively. Finally, decision curves analysis demonstrated higher benefit compared to the first-generation calculator and MRI alone. These novel RC based on MRI and BOOP may help to better select patient for prostate biopsy after prostate MRI.