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Background: Approximately 70% of bladder cancer is diagnosed as non-muscle invasive (NMIBC) and inflammation is known to impact the oncological outcomes. Adjuvant intravesical BCG in intermediate/high risk can lower recurrence and progression. The efficacy of intravesical BCG can be impacted by smoking effects on systemic inflammation., Methods: Our retrospective, multicenter study with data from 1.313 NMIBC patients aimed to assess the impact of smoking and the systemic inflammatory status on BCG response in T1G3 bladder cancer, using a machine-learning CART based algorithm., Results: In a median of 50-month follow-up (IQR 41-75), 344 patients experienced progression to muscle invasive or metastatic disease and 65 died due to bladder cancer. A CART algorithm has been employed to stratify patients in three prognostic clusters using smoking status, LMR (lymphocytes to monocytes ratio), NLR (neutrophil-to-lymphocyte ratio) and PLR (platelet-to-lymphocyte ratio) as variables. Cox regression models revealed a 1.5-fold (HR 1.66, 95%, CI 1.20-2.29, P=0.002) and three-fold (HR 2.99, 95% CI 2.08-4.30, P<0.001) risk of progression, in intermediate and high risk NMIBC respectively, compared to the low-risk group. The model's concordance index was 0.66., Conclusions: Our study provides an insight into the influence of smoking on inflammatory markers and BCG response in NMIBC patients. Our machine-learning approach provides clinicians a valuable tool for risk stratification, treatment, and decision-making. Future research in larger prospective cohorts is required for validating these findings.

Erectile Dysfunction (ED) is defined as the persistent inability to obtain and maintain an erection that enables satisfactory sexual intercourse. ED prevalence vary across age groups, affecting approximately 1-9% of men under 40, 2-9% of those aged 40-59, and increasing to 20-40% for those aged 60-69. However, it remains a frequently untreated or insufficiently treated condition. Especially due to the feeling of discomfort and guilt, patients often avoid consulting their physicians; in this context, digital innovation could potentially play a pivotal role in the diagnosis and management of ED. This narrative review depicts the ongoing status of digital innovations in ED focusing on websites, social media platforms and mobile health applications (MHA). We examined Google, social media platforms (Facebook, Twitter, YouTube, and TikTok), and the recently developed MHA apps on Google Play Store and Apple App Store. Websites provide readily available but sometimes difficult to understand information, while social media is easy to understand and act on. MHA apps are the most complete and trustworthy tool for self-care management. In conclusion, digital innovations are a continuously growing source of information and therapeutic tools., Competing Interests: Competing interests MF is a speaker for Boston Scientific. The remaining authors declare no conflict of interest., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

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.)

Background and Objective: Symptomatic benefit and urodynamic obstruction relief represent relevant outcomes of therapies for lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH). We summarized evidence from studies concurrently assessing variations in terms of symptoms severity and invasive urodynamic measures of obstruction following medical and surgical therapies for LUTS/BPH., Methods: We performed a systematic review of PubMed, Scopus, and Web of Science in June 2023., Key Findings and Limitations: We identified 29 publications: 14 (872 patients) and 15 (851 patients) studies addressing medical and surgical therapies, respectively. The mean percentage total International Prostate Symptom Score (IPSS) improvements ranged from -2.5% to 56.3% and from 35.1% to 82.1% following medical and surgical therapies, respectively. The corresponding mean percentage Bladder Outlet Obstruction Index (BOOI) improvements ranged from 7.8% to 53.5% and from 22.4% to 138.6%, respectively. Holmium laser enucleation of the prostate (HoLEP) provided IPSS improvements in the higher range and the greatest BOOI reduction., Conclusions and Clinical Implications: Globally, based on available evidence, more pronounced symptomatic benefits are observed following treatments providing greater deobstructive effect. In detail, patients undergoing surgery exhibit greater IPSS and BOOI improvements than those receiving medical therapy., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

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.)

The aim of this study is to investigate the role of [ 18 F]-PSMA-1007 PET in differentiating high- and low-risk prostate cancer (PCa) through a robust radiomics ensemble model. This retrospective study included 143 PCa patients who underwent [ 18 F]-PSMA-1007 PET/CT imaging. PCa areas were manually contoured on PET images and 1781 image biomarker standardization initiative (IBSI)-compliant radiomics features were extracted. A 30 times iterated preliminary analysis pipeline, comprising of the least absolute shrinkage and selection operator (LASSO) for feature selection and fivefold cross-validation for model optimization, was adopted to identify the most robust features to dataset variations, select candidate models for ensemble modelling, and optimize hyperparameters. Thirteen subsets of selected features, 11 generated from the preliminary analysis plus two additional subsets, the first based on the combination of robust and fine-tuning features, and the second only on fine-tuning features were used to train the model ensemble. Accuracy, area under curve (AUC), sensitivity, specificity, precision, and f-score values were calculated to provide models' performance. Friedman test, followed by post hoc tests corrected with Dunn-Sidak correction for multiple comparisons, was used to verify if statistically significant differences were found in the different ensemble models over the 30 iterations. The model ensemble trained with the combination of robust and fine-tuning features obtained the highest average accuracy (79.52%), AUC (85.75%), specificity (84.29%), precision (82.85%), and f-score (78.26%). Statistically significant differences (p < 0.05) were found for some performance metrics. These findings support the role of [ 18 F]-PSMA-1007 PET radiomics in improving risk stratification for PCa, by reducing dependence on biopsies., (© 2024. The Author(s).)

RNAs, especially non-coding RNAs (ncRNAs), are crucial players in regulating cellular mechanisms due to their ability to interact with and regulate other molecules. Altered expression patterns of ncRNAs have been observed in prostate cancer (PCa), contributing to the disease's initiation, progression, and treatment response. This study aimed to evaluate the ability of a specific set of RNAs, including long ncRNAs (lncRNAs), microRNAs (miRNAs), and mRNAs, to discriminate between PCa and the non-neoplastic condition benign prostatic hyperplasia (BPH). After selecting by literature mining the most relevant RNAs differentially expressed in biofluids from PCa patients, we evaluated their discriminatory power in samples of unfiltered urine from 50 PCa and 50 BPH patients using both real-time PCR and droplet digital PCR (ddPCR). Additionally, we also optimized a protocol for urine sample manipulation and RNA extraction. This two-way validation study allowed us to establish that miRNAs (i.e., miR-27b-3p, miR-574-3p, miR-30a-5p, and miR-125b-5p) are more efficient biomarkers for PCa compared to long RNAs (mRNAs and lncRNAs) (e.g., PCA3, PCAT18, and KLK3), as their dysregulation was consistently reported in the whole urine of patients with PCa compared to those with BPH in a statistically significant manner regardless of the quantification methodology performed. Moreover, a significant increase in diagnostic performance was observed when molecular signatures composed of different miRNAs were considered. Hence, the abovementioned circulating ncRNAs represent excellent potential non-invasive biomarkers in urine capable of effectively distinguishing individuals with PCa from those with BPH, potentially reducing cancer overdiagnosis.

Background: Surgical treatment of symptomatic benign prostatic hyperplasia (BPH) has seen an evolution during the last decades. On one hand, en-bloc HoLEP emerged as a valid endoscopic treatment regardless prostate size. On the other hand, robot-assisted simple prostatectomy (RASP) has gained attention in larger prostates showing encouraging results. Herein, for the first time in the scientific scenario, we sought to compare the outcomes of RASP and en-bloc HoLEP cases after propensity-score matching (PSM) analysis., Methods: We retrospectively queried our prospectively database of patients treated with HoLEP or RASP between 2017 and 2022 among two high-volume centers. PSM was applied based on the International Prostate Symptom Score (IPSS) questionnaire, prostate volume and max-flow rate. All procedures were performed by a single surgeon per center. Outcomes were assessed at 1, 3, and 6-month postoperatively and therefore annually. Trifecta definition was used to assess "success" in surgical procedures and was defined as the contemporary presence of: a) no postoperative complications within the first postoperative month; b) 1-month postoperative Qmax >15 ml/s and c) no urinary incontinence at 3-month evaluation., Results: Overall, 48 HoLEP and 47 RASPs were matched. Operative time, hospitalization time (median 4 vs 5 days) and catheterization time (median 3 vs 2 day) were found to be shorter in the HoLEP group as compared to the counterpart (p < 0.05). Early postoperative complication rate was also lower in the HoLEP cohort (6.2% vs 12.6%; p = 0.03) as well as postoperative haemoglobine blood level drop (1.4 vs 2.4 g/dL; p = 0.03). On the other hand, postoperative antegrade ejaculation (55.3% vs 6.8%) 1-month max flow (median 28 vs 24 ml/sec) and continence rates (0% vs 20.8%) favored RASP (p < 0.05). Overall, Trifecta rate was similar in the two groups (76.1% vs 82.6%)., Conclusion: Both HoLEP and RASP are safe and effective treatments for symptomatic BPH. HoLEP demonstrated to have lower perioperative risks while is affecting by a higher probability of transient early UI. On the other hand, RASP is more effective in reducing postoperative ejaculatory dysfunction., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Placebo influence on such objective indicators, as sperm quality and infertility, has not been studied previously, but some studies report that placebo may distort even objective outcomes. The aim of current study is to assess the placebo effect on fertility in patients suffering from sperm abnormalities and/or infertility., Evidence Acquisition: We conducted a search of two databases (Scopus and MEDLINE) and identified placebo-controlled clinical trials which focused on sperm abnormalities and/or male infertility treatment. Primary outcomes included changes in semen parameters (volume, total count, sperm concentration in semen, progressive motility, morphology (normal cells)). Secondary outcomes included DNA fragmentation and change in pregnancy rate., Evidence Synthesis: Seventy-seven articles published from 1983 to 2022 were included. Statistically significant changes were observed for the following values: total sperm count, mean change 0.16 (95% CI 0.05, 0.26); P=0.004, I 2 =75.1%; and progressive motility, mean change 0.13 (95% CI 0.02, 0.24); P=0.026, I 2 =84.9%. In contrast, placebo did not affect sperm concentration, sperm volume, sperm morphology or DNA fragmentation index. The publication bias for all the values measured with Egger's test and funnel plots was low., Conclusions: The current meta-analysis indicated a statistically significant increase of total sperm count and progressive motility in the placebo group. In contrast, placebo did not affect sperm concentration, sperm volume, sperm morphology and DNA fragmentation index. These findings should be considered while planning or analyzing placebo-controlled clinical trials.

Solid organ transplant recipients exhibit an elevated incidence of erectile dysfunction, attributed to comorbidities and specific factors associated with organ failure. While treatment mirrors the general population's, response rates are lower, and there is a heightened concern about implanting a penile prosthesis in immunocompromised patients due to the potential occurrence of severe complications. The aim of this study was to assess the safety of penile prostheses in this population. Among fourteen included studies, ten were case reports or series of cases, and four were non randomized case-control studies with non-transplanted patients as controls. Complications affected 34 patients (11.15%), with mechanical device failures in 18 cases (5.9%) and infections in 13 cases (4.26%). Most infections required hospitalization, antibiotic treatment, and prosthesis removal, with two cases of life-threatening Fournier's gangrene. Case-control studies revealed no differences in overall reoperation rates between transplant recipients and controls. However, pelvic organ transplant recipients undergoing three-piece prosthesis implantation showed higher complications rates related to reservoir issues. Despite limited evidence, case-control studies demonstrated a generally low/moderate risk of bias within each specific domain, although overall bias was moderate/severe. As a result, clinicians may mitigate concerns regarding penile prosthesis implantation in solid organ transplant recipients., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

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.)

Purpose: Augmented adiposity may negatively impact sexual sphere through its metabolic effects and its detrimental impact on reproductive hormones. Moreover, a dysregulated metabolic pathway may promote apoptosis among spermatogenic cells. Based on these premises, a relation between weights loss and ameliorate semen parameters seems beneficial. To investigate if physical activity may affect semen parameters and fertility rate, a systematic literature search on major dataset has been performed., Materials and Methods: The search terms included: "Assisted reproduction therapies," "fertility," "semen parameters," "sperm parameters," and "physical activity." This analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines and it was registered on PROSPERO (CRD42023384471). A total of 47 studies have been identified; 1 reference has been eliminated after duplication check. After preliminary screening 32 papers have been excluded. Considering the exclusion criteria, 15 full-text articles were evaluated for eligibility. After a full-text review, six studies published during a span of eight years (2014-2022) have been included in the meta-analysis. Semen parameters, pregnancy and birth rates were investigated. The revised Cochrane risk of bias tool (Rob2) has been used to check the risk of bias., Results: The number of patients enrolled in studies ranges from 17 to 521; in the end, a total of 1,637 patients have been enrolled in the study. Fertility parameters investigated were semen quality parameters and pregnancy rates and live births. A statistically significant relationship between physical exercise and sperm concentration (p=0.02), total sperm motility (p<0.01), total sperm count (p<0.01), normal morphology (p<0.01) has been established. Moreover, the study registered a statistically significant association within physical activity and total pregnancy rate (p<0.01) and live birth rate (p<0.01)., Conclusions: We demonstrated that physical activity is significantly associated with amelioration of semen parameters and may be crucial in improving or even reverting male infertility., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Purpose: Varicocele has been associated with high seminal oxidative stress (OS), impaired semen quality, and reduced male fertility potential. However, the exact mechanism(s) underlying the development of varicocele-mediated infertility and the cause-effect relationship between varicocele and testicular dysfunction are not fully understood. The aim of this systematic review and meta-analysis (SRMA) is to investigate the impact of varicocele on testicular OS markers and sperm parameters in experimental animals with varicocele as compared to animals without varicocele., Materials and Methods: A literature search was performed using the Scopus and PubMed databases on studies that investigated testicular OS markers and sperm parameters in animals with varicocele. The primary outcomes included malondialdehyde (MDA) (nmol/mg) levels whereas the secondary outcomes included total sperm count (×10 6 ), sperm vitality (%), total sperm motility (%), and sperm DNA fragmentation (SDF) (%). Standardized mean difference (SMD) (95% confidence interval [CI]) was chosen to express the effect size. The quality of the included studies was evaluated using the Cambridge Quality Checklist., Results: Out of 76 identified articles, 6 studies on rats were included in the meta-analysis. The analysis showed a significant increase of MDA (SMD: 15.61 [1.93, 29.29]; p=0.03) in rats with varicocele vs. controls. We also observed a significant decrease in total sperm count (SMD: -17.45 [-28.97, -5.93]; p<0.01), sperm vitality (SMD: -16.41 [-26.30, -6.52]; p<0.01), total sperm motility (SMD: -17.67 [-24.90, -10.44]; p<0.01), and a significant increase of SDF (SMD: 7.41 [1.23, 13.59]; p=0.02), in rats with varicocele vs. controls. The quality of the included studies was ranked as high., Conclusions: This SRMA indicates a significant increase in levels of testicular MDA and SDF and a reduction of sperm quality in experimental animals with varicocele. These findings support the potential role of testicular OS in the development of varicocele-induced testicular damage., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

There have been many significant scientific advances in the diagnostics and treatment modalities in the field of male infertility in recent decades. Examples of these include assisted reproductive technologies, sperm selection techniques for intracytoplasmic sperm injection, surgical procedures for sperm retrieval, and novel tests of sperm function. However, there is certainly a need for new developments in this field. In this review, we discuss advances in the management of male infertility, such as seminal oxidative stress testing, sperm DNA fragmentation testing, genetic and epigenetic tests, genetic manipulations, artificial intelligence, personalized medicine, and telemedicine. The role of the reproductive urologist will continue to expand in future years to address different topzics related to diverse questions and controversies of pathophysiology, diagnosis, and therapy of male infertility, training researchers and physicians in medical and scientific research in reproductive urology/andrology, and further development of andrology as an independent specialty., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Objective: The management of chronic prostatitis/ chronic pelvic pain syndrome type III (CP/CPPS) has been always considered complex due to several biopsychological factors underlying the disease. In this clinical study, we aimed to evaluate the efficacy of the treatment with Palmitoylethanolamide, Epilobium and Calendula extract in patients with CP/CPPS III., Materials and Methods: From June 2023 to July 2023, we enrolled 45 consecutive patients affected by CP/CPPS type III in three different institution. We included patients aged between 18 and 75 years with symptoms of pelvic pain for 3 months or more before the study, a total National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score ≥ 12 point and diagnosed with NIH category III, according to 4-glass test Meares-Stamey test. Patients were then allocated to receive rectal suppositories of PEA, Epilobium and Calendula, 1 suppository/ die for 1 month. All patients have been tested with standard urinalysis in order to assess urinary leukocytes (U-WBC). The primary endpoint of the study was the reduction of NIHCPSI. The secondary outcomes were the change of peak flow, post-void residual (PVR), IIEF-5, VAS score, PSA and decrease of U-WBC., Results: A total of 45 patients concluded the study protocol. At baseline, the median age of all the patients included in the cohort was 49 years, the median PSA was 2.81 ng/ml, the median NIH-CPSI was 18.55, the median IIEF-5 was 18.27, the median U-WBC was 485.3/mmc, the median VAS score was 6.49, the median PVR was 26.5 ml and the median peak flow was 16.3 ml/s. After 1 month of therapy we observed a statistically significant improvement of NIH-CPSI, U-WBC, PSA, IIEF-5, peak flow, PVR and VAS., Conclusions: In this observational study, we showed the clinical efficacy of the treatment with PEA, Epilobium and Calendula, 1 suppository/die for 1 month, in patients with CP/CPPS III. The benefits of this treatment could be related to the reduction of inflammatory cells in the urine that could imply a reduction of inflammatory cytokines. These results should be confirmed in further studies with greater sample size.

Background and Objective: It is considered standard for authors of scientific papers to provide access to their raw data. The purpose of this study was to investigate data availability statements (DAS) and the actual availability of data in urology., Methods: The DAS policies of the top ten urology journals were retrieved. Then 190 selected papers were classified according to their DAS status. Finally, we contacted the corresponding authors of papers that stated that data were available on request to enquire about this possibility., Key Findings and Limitations: All journals either required or highly recommended a DAS. Among the selected articles, 52% (99/190) included a DAS stating data availability, most often on reasonable request to the corresponding author. A formal DAS was lacking in 29.5% (56/190) of the articles, with an additional 18.3% (35/190) citing various reasons for data unavailability. On contact, 23.4% (15/64) of corresponding authors indicated a willingness to share their data. Overall, data were unavailable in 73.7% (140/190) of cases. There was no difference between papers dealing with malignant and benign diseases., Conclusions and Clinical Implications: There is a gap between the intention to share data and actual practice in major urological journals. As data sharing plays a critical role in safeguarding the reliability of published results and in the potential for reanalysis and merging of datasets, there is a clear need for improvement. Easier access to data repositories and stronger enforcement of existing journal policies are essential., Patient Summary: To ensure the reliability of data and allow further analyses, major urology journals require authors to make their data available to other researchers when possible. However, in practice we found that data were only accessible for about a quarter of published scientific papers., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: This study aimed to investigate the effects of ejaculatory abstinence on sperm parameters., Methods: This analysis was registered in PROSPERO (CRD42023472124). We performed a search on PubMed using the following text terms: (("sperm parameters" OR "sperm analysis" [Mesh]) AND ("sperm DNA fragmentation" OR "DNA fragmentation" [Mesh]) AND ("sexual abstinence" [Mesh] OR "abstinence")) and an advanced search in Scopus using the terms ("sperm parameters" OR "sperm parameters" OR "DNA fragmentation") AND ("abstinence"). The sperm parameters that were investigated were sperm volume, total sperm motility, progressive sperm motility, sperm concentration, sperm morphology, and sperm DNA fragmentation (SDF). A two-day cut-off as a "short" or "long" abstinence period has been defined., Results: Thirteen studies published between 2013 and 2022 were included in this meta-analysis. A total of 2,315 patients, ranging from 6 to 836 from each cohort, were enrolled in the study. We showed that longer abstinence time was associated with greater sperm concentration (mean difference [MD]: 8.19; p <0.01), sperm volume (MD: 0.96; p <0.01), and higher SDF (MD: 3.46; p <0.01), but lower progressive sperm motility (MD: -1.83; p <0.01). Otherwise, no statistically significant difference was observed in patients with longer vs. shorter abstinence times regarding total sperm motility (MD: -1.83; p = 0.06). Meta-regression analysis showed that days of abstinence were positively and linearly related to sperm concentration (slope: 3.74; p <0.01) and SDF (slope: 0.65; p = 0.044)., Conclusions: According to our data, short ejaculatory abstinence is associated with better sperm quality. Indeed, a higher percentage of progressive sperm motility and lower levels of SDF have been reported in a short abstinence cohort. In contrast, the long abstinence group reported a higher sperm concentration., Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023472124., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Lo Giudice, Asmundo, Cimino, Cocci, Falcone, Capece, Abdelhameed, Capogrosso, Morgado, Tsampoukas, Manfredi and Russo.)

Background: Generative Pretrained Model (GPT) chatbots have gained popularity since the public release of ChatGPT. Studies have evaluated the ability of different GPT models to provide information about medical conditions. To date, no study has assessed the quality of ChatGPT outputs to prostate cancer related questions from both the physician and public perspective while optimizing outputs for patient consumption., Methods: Nine prostate cancer-related questions, identified through Google Trends (Global), were categorized into diagnosis, treatment, and postoperative follow-up. These questions were processed using ChatGPT 3.5, and the responses were recorded. Subsequently, these responses were re-inputted into ChatGPT to create simplified summaries understandable at a sixth-grade level. Readability of both the original ChatGPT responses and the layperson summaries was evaluated using validated readability tools. A survey was conducted among urology providers (urologists and urologists in training) to rate the original ChatGPT responses for accuracy, completeness, and clarity using a 5-point Likert scale. Furthermore, two independent reviewers evaluated the layperson summaries on correctness trifecta: accuracy, completeness, and decision-making sufficiency. Public assessment of the simplified summaries' clarity and understandability was carried out through Amazon Mechanical Turk (MTurk). Participants rated the clarity and demonstrated their understanding through a multiple-choice question., Results: GPT-generated output was deemed correct by 71.7% to 94.3% of raters (36 urologists, 17 urology residents) across 9 scenarios. GPT-generated simplified layperson summaries of this output was rated as accurate in 8 of 9 (88.9%) scenarios and sufficient for a patient to make a decision in 8 of 9 (88.9%) scenarios. Mean readability of layperson summaries was higher than original GPT outputs ([original ChatGPT v. simplified ChatGPT, mean (SD), p-value] Flesch Reading Ease: 36.5(9.1) v. 70.2(11.2), <0.0001; Gunning Fog: 15.8(1.7) v. 9.5(2.0), p < 0.0001; Flesch Grade Level: 12.8(1.2) v. 7.4(1.7), p < 0.0001; Coleman Liau: 13.7(2.1) v. 8.6(2.4), 0.0002; Smog index: 11.8(1.2) v. 6.7(1.8), <0.0001; Automated Readability Index: 13.1(1.4) v. 7.5(2.1), p < 0.0001). MTurk workers (n = 514) rated the layperson summaries as correct (89.5-95.7%) and correctly understood the content (63.0-87.4%)., Conclusion: GPT shows promise for correct patient education for prostate cancer-related contents, but the technology is not designed for delivering patients information. Prompting the model to respond with accuracy, completeness, clarity and readability may enhance its utility when used for GPT-powered medical chatbots., (© 2024. The Author(s).)

Introduction: Benign Prostate Hyperplasia (BPH) significantly impacts men's health and quality of life, with its prevalence rising with age. This review critically examines the cost-effectiveness of pharmacological interventions for BPH to optimize patient outcomes and healthcare resource utilization., Areas Covered: This review explores the integration of cost-effectiveness analysis (CEA) into clinical practice, balancing clinical efficacy with economic efficiency in BPH management. We performed a critical literature search, including recent studies on the economic evaluation of BPH treatments, focusing on pharmacotherapies such as alpha-blockers and 5-alpha reductase inhibitors. Additionally, we discussed the concept of CEA and evaluated the role of medicinal reconciliation and the avoidance of polypharmacy in favor of optimal BPH treatment., Expert Opinion: Cost-effectiveness analysis is crucial for evaluating BPH treatments, with evidence suggesting a shift towards surgical interventions may offer greater long-term economic benefits. However, these models must be applied cautiously, considering clinical evidence and patient preferences to ensure equitable and patient-centric healthcare.

Peyronie's disease (PD) is a condition of penile connective tissue affecting up to 10% of men worldwide. In the complexity of its management, nonsurgical treatments, such as intraplaque injections, are gaining attention. The current literature shows data on the efficacy of intraplaque injections of hyaluronic acid (HA) mainly in acute-phase PD. However, data on injections of HA in stable-phase PD are lacking. Data for this retrospective study were derived from a prospectively maintained database of private patients presenting at a private medical practice affiliated to the University of Naples "Federico II" (Naples, Italy) with stable-phase PD between January 2020 and March 2023. Patients underwent a standard protocol of three injections, each administered at a two-week interval. During the intervals, patients performed vacuum device therapy, penile stretching, and modeling exercises. All patients compiled the Peyronie's Disease Questionnaire (PDQ) and Global Assessment of Peyronie's Disease (GAPD) at baseline and 2 weeks after the third injection. A penile Doppler ultrasound was performed 2 weeks after the last injection to record the final curvature. Overall, we recruited 62 patients with stable-phase PD and a mean (±standard deviation [s.d.]) curvature of 52.7° (±9.7°). After 6 weeks, eight (12.9%) patients did not experience any curvature improvement. The remaining 54 patients had a final mean (±s.d.) curvature of 40.3° (±9.1°) with P < 0.001, compared to that before treatment. We found improvement in all PDQ domains (all P ≤ 0.01), and 50 (80.6%) patients reported subjective improvement of the penile curvature according to the GAPD. In conclusion, we demonstrated that after three injections of HA administered according to the adopted protocol, patients with stable-phase PD could experience significant improvements in penile curvature, and physical and psychological consequences of the disease without significantly relevant side effects., (Copyright © 2024 Copyright: © The Author(s)(2024).)

Context: Recommendations regarding the management of penile size abnormalities and dysmorphophobia are important in guiding evidence-based clinical practice., Objective: To present a summary of the 2023 European Association of Urology sexual and reproductive health evidence-based recommendations for the management of penile size abnormalities and dysmorphophobia., Evidence Acquisition: A broad and comprehensive scoping exercise covering all areas of the guidelines was performed. Databases searched included Medline, EMBASE, and the Cochrane Libraries. A level of evidence and a strength of recommendation were assigned for each recommendation according to the evidence identified. The evidence cutoff date for the 2023 guidelines is June 1, 2022., Evidence Synthesis: Well-structured studies reporting high level of evidence, with standardized PROMS were deficient on penile size abnormalities and dysmorphohobia. A shared definition for short penis/micropenis was also lacking. Categorisation of penile abnormalities according to congenital, acquired, and dysmorphophobic aetiology is deemed compulsory. A detailed medical and psychosexual history and precise measurements of penile size are essential in the diagnostic pathway. Patients with normal penile size who are seeking penile augmentation should be referred for psychological evaluation for potential dysmorphophobic disorders. Penile length and girth enhancements can be achieved via a multitude of treatments, but a personalised management plan is crucial for satisfactory results. Endocrinological therapies, when indicated, are effective in the prepubertal setting only. Vacuum therapy has a limited evidence base in treatment protocols, although acceptable outcomes have been reported for penile traction therapy. Surgical techniques to enhance penile length and girth have limited evidence and should only be proposed after extensive patient counselling., Conclusions: Management of penile abnormalities and dysmorphophobia is a complex issue with considerable ethical concerns. The adoption of a structured diagnostic and therapeutic pathway is crucial, as recommended in the guidelines., Patient Summary: Requests for medical/surgical treatments to increase penis size have increased dramatically worldwide. Several conservative and surgical treatments are available. However, few patients receive clear information on the benefits and possible harms of these treatments. These guidelines aim to provide a structured path to guide both physicians and patients in the selection of appropriate treatment(s) to increase penis size., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

We aimed to analyze the association between CYP7B1 and prostate cancer, along with its association with proteins involved in cancer and metabolic processes. A retrospective analysis was performed on 390 patients with prostate cancer (PC) or benign prostatic hyperplasia (BPH). We investigated the interactions between CYP7B1 expression and proteins associated with PC and metabolic processes, followed by an analysis of the risk of biochemical recurrence based on CYP7B1 expression. Of the 139 patients with elevated CYP7B1 expression, 92.8% had prostate cancer. Overall, no increased risk of biochemical recurrence was associated with CYP7B1 expression. However, in a non-diabetic subgroup analysis, higher CYP7B1 expression indicated a higher risk of biochemical recurrence, with an HR of 1.78 (CI: 1.0-3.2, p = 0.05). PC is associated with elevated CYP7B1 expression. In a subgroup analysis of non-diabetic patients, elevated CYP7B1 expression was associated with an increased risk of biochemical recurrence, suggesting increased cancer aggressiveness.

Background: In 2020, 38% of adults were affected by obesity, while infertility globally affected 1 in 6 people at some stage of their lives.Body mass index (BMI) provides an easy but occasionally inaccurate estimation of body composition. To achieve a more precise assessment, bioelectric impedance analysis serves as a validated tool that administers electrical energy through surface electrodes. Phase angle as a function of the relationship between tissues resistance and reactance, is a trustworthy predictor of body composition and cell membrane integrity., Objectives: We aim to assess whether there is an association between phase angle and seminal parameters, as well as sperm DNA fragmentation percentage., Design: Semen samples of 520 idiopathic infertile patients were analyzed according to 2021 World Health Organization guidelines and evaluated for sperm DNA fragmentation rate. Each participants underwent bioelectric impedance analysis., Results: Median age was 40 years old, median BMI was 26.3 kg/m2, median phase angle was 6.2°. In the logistic regression analysis adjusted for age and total intracorporeal water, phase angle (continuous) was significantly associated with oligozoospermia (odds ratio [OR]:0.4; p<0.01) and sperm morphology (OR: 0.65; p=0.05) and slightly with sperm DNA fragmentation (OR: 0.98; p=0.07). In subgroup analysis, the logistic regression analysis adjusted for the mentioned parameters showed that a phase angle between 6.2 and 7 (°) (OR: 0.63; p=0.02) and >7 (°) (OR: 0.12; p<0.01) were associated with a reduced risk of oligozoospermia compared to values <6.2 (°). Similarly, a phase angle between 6.2 and 7 (°) (OR: 0.57; p< 0.01 and OR: 0.58; p= 0.01) and PA > 7 (°) (OR: 0.12; p= 0.03 and OR: 0.21; p< 0.01) were associated with a reduced risk of lower sperm concentration and lower total sperm count, respectively, compared to a phase angle < 6.2 (°)., Conclusion: Our study suggests a negative association between phase angle and detrimental sperm parameters in male idiopathic infertility., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Liprino, Giacone, Lombardo, Asmundo, Russo, Abdelhameed, Cimino, Guglielmino and Chamayou.)

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: Quality of Life and Sexuality with Penile Prosthesis (QoLSPP) is the first validated questionnaire to specifically evaluate the satisfaction of patients undergoing penile prosthesis implantation. Our primary aim was to conduct a systematic review and pooled analysis of articles reporting QoLSPP., Evidence Acquisition: A comprehensive bibliographic search on the MEDLINE, Scopus, Web of Science, and Cochrane Library databases was performed in April 2023. Studies were selected if they assessed male subjects (P) undergoing penile prosthesis implantation (I) with or without comparison with other treatments (C), reporting the patient satisfaction according to QoLSPP (O). Prospective and retrospective original studies were included (S). The risk of bias was assessed using the ROBINS-I tool and the Knoll method. Means and standard deviations (SDs) of QoLSPP scores were included in the pooled analysis. PROSPERO ID: "CRD42023427261.", Evidence Synthesis: A total of 10 studies investigating 1105 patients were included in the systematic review; of these, eight articles describing the outcomes of 693 subjects were eligible for the pooled analysis. Overall serious risk of bias was found in 2/3 of nonrandomized comparative studies (66%), while seven single-arm studies (100%) were classified as having a high risk of bias. Pooled analysis of the QoLSPP-Functional domain revealed an overall effect size (ES) of 4.22 points (95% CI 4.04-4.40; P<0.001). The QoLSPP-Relational pooled score was 4.17 points (95% CI 4.03-4.31; P<0.001). The QoLSPP-Social pooled score corresponded to 4.21 points (95% CI 4.02-4.40; P<0.001). Pooled analysis of the QoLSPP-Personal domain showed an overall ES of 3.97 points (95% CI 3.61-4.32; P<0.001). There was insufficient data to pool QoLSPP total scores., Conclusions: Patients undergoing penile prosthesis implantation report positive scores in all QoLSPP domains, demonstrating high satisfaction levels. Future studies are needed to improve the evidence on the topic.

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.)

Objective: To evaluate transperineal laser ablation (TPLA) with Echolaser® (Echolaser® TPLA, Elesta S.p.A., Calenzano, Italy) as a treatment for benign prostatic hyperplasia (BPH) and prostate cancer (PCa) using the Delphi consensus method., Methods: Italian and international experts on BPH and PCa participated in a collaborative consensus project. During two rounds, they expressed their opinions on Echolaser® TPLA for the treatment of BPH and PCa answering online questionnaires on indications, methodology, and potential complications of this technology. Level of agreement or disagreement to reach consensus was set at 75%. If the consensus was not achieved, questions were modified after each round. A final round was performed during an online meeting, in which results were discussed and finalized., Results: Thirty-two out of forty invited experts participated and consensus was reached on all topics. Agreement was achieved on recommending Echolaser® TPLA as a treatment of BPH in patients with ample range of prostate volume, from <40 mL (80%) to >80 mL (80%), comorbidities (100%), antiplatelet or anticoagulant treatment (96%), indwelling catheter (77%), and strong will of preserving ejaculatory function (100%). Majority of respondents agreed that Echolaser® TPLA is a potential option for the treatment of localized PCa (78%) and recommended it for low-risk PCa (90%). During the final round, experts concluded that it can be used for intermediate-risk PCa and it should be proposed as an effective alternative to radical prostatectomy for patients with strong will of avoiding urinary incontinence and sexual dysfunction. Almost all participants agreed that the transperineal approach of this organ-sparing technique is safer than transrectal and transurethral approaches typical of other techniques (97% of agreement among experts). Pre-procedural assessment, technical aspects, post-procedural catheterization, pharmacological therapy, and expected outcomes were discussed, leading to statements and recommendations., Conclusion: Echolaser® TPLA is a safe and effective procedure that treats BPH and localized PCa with satisfactory functional and sexual outcomes., Competing Interests: The authors declare no conflict of interest., (© 2024 Editorial Office of Asian Journal of Urology. Production and hosting by Elsevier B.V.)

Purpose: Varicoceles can be a source of elevated seminal oxidative stress (OS) and sperm DNA fragmentation (SDF). However, it remains unclear whether varicocele repair (VR) could reduce these parameters. This systematic review and meta-analysis (SRMA) aims to investigate the impact of VR on SDF and seminal malondialdehyde (MDA)., Materials and Methods: A literature search was performed in Scopus, PubMed, Ovid, Embase, and Cochrane databases. This SRMA included randomized controlled trials and observational studies reporting the pre- and postoperative levels of SDF and seminal OS in infertile men with clinical varicocele that underwent VR. Subgroup analyses included techniques of VR and SDF testing. The effect size was expressed as standardized mean difference (SMD)., Results: Out of 1,632 abstracts assessed for eligibility, 29 studies with 1,491 infertile men were included. The analysis showed a significant reduction in SDF after VR, compared to preoperative values (SMD -1.125, 95% confidence interval [CI] -1.410, -0.840; p<0.0001) with high inter-study heterogeneity (I²=90.965%). Reduction in SDF was evident with microsurgical technique and non-microsurgical inguinal approaches (SMD -1.014, 95% CI -1.263, -0.765; p<0.0001, and SMD -1.495, 95% CI -2.116, -0.873; p<0.0001), respectively. Reduction in SDF was significant irrespective of testing was done by sperm chromatin dispersion (SMD -2.197, 95% CI -3.187, -1.207; p<0.0001), sperm chromatin structure assay (SMD -0.857, 95% CI -1.156, -0.559; p<0.0001) or TUNEL (SMD -1.599, 95% CI -2.478, -0.719; p<0.0001). A significant decrease in seminal MDA levels was observed following VR (SMD -2.450, 95% CI -3.903 to -0.997, p=0.001) with high inter-study heterogeneity (I²=93.7%)., Conclusions: Using pre- and post-intervention data, this SRMA indicates a significant reduction in SDF and seminal MDA levels in infertile men with clinical varicocele treated with VR. These findings may have important implications for the future management of this selected group of infertile patients., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

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.)

Background: The proportion of health-related searches on the internet is continuously growing. ChatGPT, a natural language processing (NLP) tool created by OpenAI, has been gaining increasing user attention and can potentially be used as a source for obtaining information related to health concerns. This study aims to analyze the quality and appropriateness of ChatGPT's responses to Urology case studies compared to those of a urologist., Methods: Data from 100 patient case studies, comprising patient demographics, medical history, and urologic complaints, were sequentially inputted into ChatGPT, one by one. A question was posed to determine the most likely diagnosis, suggested examinations, and treatment options. The responses generated by ChatGPT were then compared to those provided by a board-certified urologist who was blinded to ChatGPT's responses and graded on a 5-point Likert scale based on accuracy, comprehensiveness, and clarity as criterias for appropriateness. The quality of information was graded based on the section 2 of the DISCERN tool and readability assessments were performed using the Flesch Reading Ease (FRE) and Flesch-Kincaid Reading Grade Level (FKGL) formulas., Results: 52% of all responses were deemed appropriate. ChatGPT provided more appropriate responses for non-oncology conditions (58.5%) compared to oncology (52.6%) and emergency urology cases (11.1%) (p = 0.03). The median score of the DISCERN tool was 15 (IQR = 5.3) corresponding to a quality score of poor. The ChatGPT responses demonstrated a college graduate reading level, as indicated by the median FRE score of 18 (IQR = 21) and the median FKGL score of 15.8 (IQR = 3)., Conclusions: ChatGPT serves as an interactive tool for providing medical information online, offering the possibility of enhancing health outcomes and patient satisfaction. Nevertheless, the insufficient appropriateness and poor quality of the responses on Urology cases emphasizes the importance of thorough evaluation and use of NLP-generated outputs when addressing health-related concerns., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Conservative and medical treatments are considered the first step in ischemic priapism (IP) management, although there is no clear evidence regarding their efficacy. We conducted a systematic review on behalf of the EAU Guidelines panel on Sexual and Reproductive health to analyse the available evidence on the efficacy and safety of conservative and medical treatment for non-sickle cell disease-related IP. Databases searched for relevant literature investigating efficacy and safety of conservative measures and medical treatment for IP included Medline, EMBASE, Cochrane Libraries and clinicaltrial.gov published up to September 2021. Overall, 41 retrospective, 3 prospective single-arm studies and 3 randomized controlled trials met the inclusion criteria. Intracavernous injection with sympathomimetic (ICIs) agents were the most frequently utilized treatment with efficacy ranging from 0 to 100% of cases. The combination of ICIs with corporeal aspiration with or without irrigation with saline was successful in 70 to 100% of cases. Oral treatment with β2 receptor agonist (e.g., terbutaline) showed mild to moderate efficacy. Conservative methods including ice pack, exercise, cold enema and ejaculation depicted lower effectiveness in resolving priapism (1-55%). Longer time interval from the onset to the resolution of IP was associated with higher rate of erectile dysfunction at follow-up (30-70%), especially after 24 h., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Patients' treatment preferences (PTP) depend on the complex interaction of numerous patient- and treatment-related factors; their assessment can guide therapy and promote compliance of patients with erectile dysfunction (ED). We aimed to systematically describe the literature evaluating the treatment preferences of patients with ED, published in the last 25 years., Evidence Acquisition: A comprehensive bibliographic search of multiple databases was conducted in June, 2023. The literature search was limited to the articles published since 1998. Articles were deemed eligible if they described male patients with ED (P) undergoing treatment for this condition (I) compared with other treatments, placebo or sham therapy (C), and reported PTP (O). Only randomized controlled trials (RCTs) and post-hoc analyses of RCTs were selected (S). The data were presented in a narrative fashion. The risk of bias (RoB) was evaluated using the RoB 2 tool and the Mulhall-Montorsi model., Evidence Synthesis: A total 14 RCTs evaluating 6,841 patients and 4 post-hoc analyses of RCTs were included. All RCTs were considered to be at high RoB. No validated tool was used to investigate PTP. Sildenafil was the most frequently evaluated ED treatment (9 RCTs). Sildenafil was chosen over placebo by 78-100% of subjects and over ICI in 70% of patients due to its easier route of administration. No significant difference in patient preference was recorded between Sildenafil tablets and orodispersible (53% vs. 47%, P>0.05). Tadalafil was preferred over Sildenafil by 66-73% of patients (P<0.05), mainly because it allowed an erection long after taking the drug (55-67%). Tadalafil as-needed was chosen over Tadalafil 3 times/week by 57-59% of the patients (P<0.05)., Conclusions: The available RCTs support the preference of ED patients for Sildenafil over ICI, Tadalafil over Sildenafil, and Tadalafil as-needed over Tadalafil 3 times/week. However, these findings should be considered at high RoB.

Sickle cell disease (SCD) is an inherited hemoglobin disorder characterized by the occlusion of small blood vessels by sickle-shaped red blood cells. SCD is associated with a number of complications, including ischemic priapism. While SCD accounts for at least one-third of all priapism cases, no definitive treatment strategy has been established to specifically treat patients with SC priapism. The aim of this systematic review was to assess the efficacy and safety of contemporary treatment modalities for acute and stuttering ischemic priapism associated with SCD. The primary outcome measures were defined as resolution of acute priapism (detumescence) and complete response of stuttering priapism, while the primary harm outcome was as sexual dysfunction. The protocol for the review has been registered (PROSPERO Nr: CRD42020182001), and a systematic search of Medline, Embase, and Cochrane controlled trials databases was performed. Three trials with 41 observational studies met the criteria for inclusion in this review. None of the trials assessed detumescence, as a primary outcome. All of the trials reported a complete response of stuttering priapism; however, the certainty of the evidence was low. It is clear that assessing the effectiveness of specific interventions for priapism in SCD, well-designed, adequately-powered, multicenter trials are strongly required., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Surgical treatments for ischemic priapism (IP) include shunts or penile implants. Non-ischemic priapism (NIP) is usually the result of penile/perineal trauma causing an arterial fistula and embolisation may be required. We conducted a systematic review on behalf of the EAU Sexual and Reproductive health Guidelines panel to analyse the available evidence on efficacy and safety of surgical modalities for IP and NIP. Outcomes were priapism resolution, sexual function and adverse events following surgery. Overall, 63 studies (n = 923) met inclusion criteria up to September 2021. For IP (n = 702), surgery comprised distal (n = 274), proximal shunts (n = 209) and penile prostheses (n = 194). Resolution occurred in 18.7-100% for distal, 5.7-100% for proximal shunts and 100% for penile prostheses. Potency rate was 20-100% for distal, 11.1-77.2% for proximal shunts, and 26.3-100% for penile prostheses, respectively. Patient satisfaction was 60-100% following penile prostheses implantation. Complications were 0-42.5% for shunts and 0-13.6% for IPP. For NIP (n = 221), embolisation success was 85.7-100% and potency 80-100%. The majority of studies were retrospective cohort studies. Risk of bias was high. Overall, surgical shunts have acceptable success rates in IP. Proximal/venous shunts should be abandoned due to morbidity/ED rates. In IP > 48 h, best outcomes are seen with penile prostheses implantation. Embolisation is the mainstay technique for NIP with high resolution rates and adequate erectile function., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Prostate cancer (PCa) is a prevalent malignancy affecting men worldwide, and plant-based diets have been widely advocated for their health benefits. The aim of this study was to test the association between general, healthy, and unhealthy pro-vegetarian plant-based diets and PCa severity on 118 consecutive patients undergoing prostatectomy in a university hospital in Italy. Food frequency questionnaires were used to calculate scores for dietary patterns. Multivariate logistic regression analyses were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to test the associations. A general plant-based diet was not associated with cancer severity, while patients reporting a higher adherence to a healthy plant-based diet were less likely to have a more severe PCa (for medium/high vs. low-risk PCa, OR = 0.27, 95% CI: 0.08, 0.88; for high vs. medium/low-risk PCa, OR = 0.09, 95% CI: 0.02, 0.39). Patients resulting in higher adherence to an unhealthy plant-based diet were more likely to be diagnosed with more severe PCa (OR = 6.15, 95% CI: 1.70, 22.24). In conclusion, plant-based dietary patterns may have a different impact on PCa severity depending on the quality of the foods included.

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.)

Artificial intelligence (AI) in medicine has gained a lot of momentum in the last decades and has been applied to various fields of medicine. Advances in computer science, medical informatics, robotics, and the need for personalized medicine have facilitated the role of AI in modern healthcare. Similarly, as in other fields, AI applications, such as machine learning, artificial neural networks, and deep learning, have shown great potential in andrology and reproductive medicine. AI-based tools are poised to become valuable assets with abilities to support and aid in diagnosing and treating male infertility, and in improving the accuracy of patient care. These automated, AI-based predictions may offer consistency and efficiency in terms of time and cost in infertility research and clinical management. In andrology and reproductive medicine, AI has been used for objective sperm, oocyte, and embryo selection, prediction of surgical outcomes, cost-effective assessment, development of robotic surgery, and clinical decision-making systems. In the future, better integration and implementation of AI into medicine will undoubtedly lead to pioneering evidence-based breakthroughs and the reshaping of andrology and reproductive medicine., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Conditions referred to as 'male sexual dysfunctions' usually include erectile dysfunction, ejaculatory disorders and male hypogonadism. However, some less common male sexual disorders exist, which are under-recognized and under-treated, leading to considerable morbidity, with adverse effects on individuals' sexual health and relationships. Such conditions include post-finasteride syndrome, restless genital syndrome, post-orgasmic illness syndrome, post-selective serotonin reuptake inhibitor (SSRI) sexual dysfunction, hard-flaccid syndrome, sleep-related painful erections and post-retinoid sexual dysfunction. Information about these disorders usually originates from case-control trials or small case series; thus, the published literature is scarce. As the aetiology of these diseases has not been fully elucidated, the optimal investigational work-up and therapy are not well defined, and the available options cannot, therefore, adequately address patients' sexual problems and implement appropriate treatment. Thus, larger-scale studies - including prospective trials and comprehensive case registries - are crucial to better understand the aetiology, prevalence and clinical characteristics of these conditions. Furthermore, collaborative efforts among researchers, health-care professionals and patient advocacy groups will be essential in order to develop evidence-based guidelines and novel therapeutic approaches that can effectively address these disorders. By advancing our understanding and refining treatment strategies, we can strive towards improving the quality of life and fostering healthier sexual relationships for individuals suffering from these rare sexual disorders., (© 2023. Springer Nature Limited.)

Background: Despite the existence of conservative therapies for Peyronie's disease (PD), surgery is commonly utilized for the treatment of bothersome curvatures due to its potential effectiveness, although it carries intrinsic risks and may not universally lead to satisfactory outcomes., Aim: To explore the rate and factors influencing patients' willingness to undergo surgery for PD., Methods: Data were prospectively collected in 5 European academic centers between 2016 and 2020. Data included age, time from PD onset, penile pain, curvature degree, difficulty at penetration, hourglass deformity, erectile dysfunction (ED), and previous treatments. All patients were offered conservative treatments, either medications or injections. Tunical shortening or lengthening procedures were offered as an alternative to conservative treatments, when indicated. Penile prosthesis was offered to those with concomitant ED. Patients' attitudes with surgery were recorded. Logistic regression analyses tested the profile of patients who were more likely to be willing to undergo surgery., Outcomes: Patients' willingness to undergo surgery for PD., Results: This study included 343 patients with a median age of 57.3 years (IQR, 49.8-63.6) and a median penile curvature of 40.0° (IQR, 30.0°-65.0°). Overall, 161 (47%) experienced penetration difficulties and 134 (39%) reported ED. Additionally, hourglass deformity and penile shortening were reported by 48 (14%) and 157 (46%), respectively. As for previous treatments, 128 (37%) received tadalafil once daily; 54 (16%) and 44 (13%), intraplaque verapamil and collagenase injections; and 30 (9%), low-intensity shock wave therapy. Significant curvature reduction (≥20°) was observed in 69 (20%) cases. Only 126 (37%) patients were open to surgery for PD when suggested. At logistic regression analysis after adjusting for confounders, younger age (odds ratio [OR], 0.97; 95% CI, 0.95-1.00; P = .02), more severe curvatures (OR, 1.04; 95% CI, 1.03-1.06; P < .0001), and difficulty in penetration (OR, 1.88; 95% CI, 1.04-3.41; P = .03) were associated with a greater attitude to consider surgical treatment., Clinical Implications: The need for effective nonsurgical treatments for PD is crucial, as is comprehensive patient counseling regarding surgical risks and benefits, particularly to younger males with severe curvatures., Strengths and Limitations: Main limitations are the cross-sectional design and the potential neglect of confounding factors., Conclusions: Patients with PD, having a lower inclination toward surgery, emphasize the need for effective nonsurgical alternatives and accurate counseling on the risks and benefits of PD surgery, particularly for younger men with severe curvatures., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Radiomics shows promising results in supporting the clinical decision process, and much effort has been put into its standardization, thus leading to the Imaging Biomarker Standardization Initiative (IBSI), that established how radiomics features should be computed. However, radiomics still lacks standardization and many factors, such as segmentation methods, limit study reproducibility and robustness., Aim: We investigated the impact that three different segmentation methods (manual, thresholding and region growing) have on radiomics features extracted from 18 F-PSMA-1007 Positron Emission Tomography (PET) images of 78 patients (43 Low Risk, 35 High Risk). Segmentation was repeated for each patient, thus leading to three datasets of segmentations. Then, feature extraction was performed for each dataset, and 1781 features (107 original, 930 Laplacian of Gaussian (LoG) features, 744 wavelet features) were extracted. Feature robustness and reproducibility were assessed through the intra class correlation coefficient (ICC) to measure agreement between the three segmentation methods. To assess the impact that the three methods had on machine learning models, feature selection was performed through a hybrid descriptive-inferential method, and selected features were given as input to three classifiers, K-Nearest Neighbors (KNN), Support Vector Machines (SVM), Linear Discriminant Analysis (LDA), Random Forest (RF), AdaBoost and Neural Networks (NN), whose performance in discriminating between low-risk and high-risk patients have been validated through 30 times repeated five-fold cross validation., Conclusions: Our study showed that segmentation methods influence radiomics features and that Shape features were the least reproducible (average ICC: 0.27), while GLCM features the most reproducible. Moreover, feature reproducibility changed depending on segmentation type, resulting in 51.18% of LoG features exhibiting excellent reproducibility (range average ICC: 0.68-0.87) and 47.85% of wavelet features exhibiting poor reproducibility that varied between wavelet sub-bands (range average ICC: 0.34-0.80) and resulted in the LLL band showing the highest average ICC (0.80). Finally, model performance showed that region growing led to the highest accuracy (74.49%), improved sensitivity (84.38%) and AUC (79.20%) in contrast with manual segmentation.

Background: Changes applied to the Prostate cancer (PCa) histopathology grading, where patients with cribriform patterns (CP) may be categorized as grade group 2 and could hypothetically be surveilled. However, CP has been associated with worse oncological outcomes. The aim of our study is to systematically review and meta-analyze the available evidence on CP in PCa patients., Methods: This analysis was registered on PROSPERO (CRD42022298473). We performed a systematic literature search of PubMed, EMBASE and Scopus using Medical Subject Headings (MeSH) indexes, keyword searches, and publication types until December 2021. The search terms included: "prostate", "prostate cancer" and "cribriform". We also searched reference lists of relevant articles. Eligible studies included published journal articles that provided quantitative data on the association between cribriform patterns at radical prostatectomy and the presence of extra-prostatic extension (EPE), seminal vesicle invasion (SVI), positive surgical margins (PSM), biochemical recurrence (BCR) or cancer specific mortality (CSM)., Results: Overall, 31 studies were included for the quantitative analysis. All articles have been published during a span of 11 years (2011-2022) with a mean month of follow-up of 62.87 months. The mean quality of these studies, assessed with the Newcastle Ottawa Scale was 6.27. We demonstrated that CP was associated with greater risk of EPE (odds ratio [OR] 1.96; P < 0.0001), SVI (OR: 2.89; p < 0.01), and PSM (OR: 1.88; p < 0.0007). Our analyses showed that CP was associated with greater risk of BCR (hazard ratio [HR]: 2.14; p < 0.01) and of CSM (HR: 3.30, p < 0.01)., Conclusion: The presence of CP is associated with adverse pathology at radical prostatectomy and worse biochemical recurrence and cancer specific mortality. These results highlight the importance of a better pathologic report of CP to advise clinician for a strict follow-up in PCa patients., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: The percutaneous nephrolithotomy (PCNL) in Horseshoe kidneys (HSK) is usually performed in the prone position, allowing entry through the upper pole and providing good access to the collecting system. However, in patients with normal kidney anatomy, the supine position is reliable and safe in most cases, but it is unknown whether the supine position is adequate in patients with HSK. The purpose of this study was to describe the results of PCNL in HSK in three different surgical institutions and to evaluate the impact of supine position during surgery, comparing pre-operative and post-operative data, complications, and stone status after surgery., Material and Methods: Between 2017 and 2022, a total of 10 patients underwent percutaneous renal surgery for stone disease in HSK. All patients were evaluated pre- and post- operatively with non-contrast CT. we evaluated patients (age and gender), stones characteristics (size, number, side, site and density ), and outcomes. The change in haemoglobin, hematocrit, creatinine and eGFr were assessed between the most recent preoperative period and the first postoperative day. Procedure success was defined as stone-free or presence of ≤4 mm fragments (Clinically Insignificant residual Fragments - CIrF). Complications were registered and classified according to Clavien-dindo Grading System, during the 30 - day postoperative period and Clavien scores ≥ 3 were considered as major complications. Statistical analysis was performed using "r 4.2.1" software, with a 5% significance level. we also compared pre-operative and post-operative data using "wilcoxon signedrank test"., Results: No statistical difference was observed between preoperative and post-operative renal function data. At one post operative day CT scan, an overall success rate of 100% was registered. 9/10 patients were completely free from urolithiasis (stone-free rate: 90%), while 1/10 patients had ≤4 mm residual stone fragments (CIrF rate: 10%). No cases of intraoperative complications were registered. Post-operative complications were reported in 1/10 patients. A patient developed urosepsis (defined as SIrS with clinical signs of bacterial infections involving urogenital organs - Clavien-dindo Grade II) after procedure, and was treated with intravenous antibiotic therapy successfully.  Conclusions: This study shows that in patients with HSK mini- PCNL in supine position allows to achieve good stone free rate with a very low morbidity. According to our series, the described technique for PCNL in HSK should be an option. Nevertheless these results must be confirmed by further studies.

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.)

Background: The level of food processing has gained interest as a potential determinant of human health. The aim of this study was to assess the relationship between the level of food processing and prostate cancer severity., Methods: A sample of 120 consecutive patients were examined for the following: their dietary habits, assessed through validated food frequency questionnaires; their dietary intake of food groups, categorized according to the NOVA classification; and their severity of prostate cancer, categorized into risk groups according to European Association of Urology (EAU) guidelines. Uni- and multivariate logistic regression analyses were performed to test the association between the variables of interest., Results: Individuals reporting a higher consumption of unprocessed/minimally processed foods were less likely to have greater prostate cancer severity than those who consumed less of them in the energy-adjusted model (odds ratio (OR) = 0.38, 95% confidence interval (CI): 1.17-0.84, p = 0.017 and OR = 0.33, 95% CI: 0.12-0.91, p = 0.032 for medium/high vs. low grade and high vs. medium/low grade prostate cancers, respectively); however, after adjusting for potential confounding factors, the association was not significant anymore. A borderline association was also found between a higher consumption of ultra-processed foods and greater prostate cancer severity in the energy-adjusted model (OR = 2.11, 95% CI: 0.998-4.44; p = 0.051), but again the association was not significant anymore after adjusting for the other covariates., Conclusions: The level of food processing seems not to be independently associated with prostate cancer severity, while potentially related to other factors that need further investigation.

Purpose: In this study, we aimed to identify prognostic factors of cancer mortality in patients who received radical cystectomy and to identify genomic alterations in a sub-cohort of patients with locally advanced (pT3-4) and/or positive lymph nodes bladder cancer (BC)., Methods: We collected 101 BC samples from 2010 to 2018 who previously received radical cystectomy. Immunohistochemical slides were evaluated for PPAR, cAMP, IMP3, Ki67, CDK4, POU5F1, Cyclin E and MDM2, p65, CD3, CD4, CD8, CD20, CD68, CD163, FOXP3, PD-1 and PD-L1 expression. We calculated a prognostic score (PS) based on the positivity to PD-1, PD-L1 and of cAMP (final score ranging from 0 to 3). DNA of each sample have been used for sequencing by NGS in a sub-cohort of 6 patients with locally advanced (pT3-4) and/or positive lymph nodes BC., Results: PD-1 + (HR [hazard ratio] 2.59; p = 0.04), PD-L1 + (HR = 6.46; p < 0.01) and cAMP + (HR 3.04; p = 0.02) were independent predictors of cancer-specific mortality (CSM). Increase of PS (score = 0 as reference) was associated with CSM, 0.81 (p = 0.80), 4.72 (p = 0.01) and 10.51 (p < 0.0) for PS 1, 2 and 3, respectively. ERBB2 was the gene most frequently mutated., Conclusion: BC exhibited heterogenous protein expression and variable genomic features. Identification of expression of PD-1, PD-L1 and cAMP could help in predicting oncological outcomes., (© 2022. The Author(s).)