Effect of Sex on the Oncological Outcomes in Response to Immunotherapy and Antibody-drug Conjugates in Patients with Urothelial and Kidney Cancer: A Systematic Review and a Network Meta-analysis.

BACKGROUND AND OBJECTIVE: Immune checkpoint inhibitors (ICIs) and antibody-drug conjugates (ADCs) herald a transformative era in metastatic renal cell carcinoma (RCC) and transitional cell carcinoma (TCC) treatment, amid acknowledged sex-based disparities in these cancers. We conducted a systematic review and network meta-analysis (NMA) to identify sex-specific differences in the efficacy of ICI/ADC monotherapy or combination therapies for RCC and TCC survival, in metastatic and adjuvant settings. METHODS: A systematic search was conducted up to October 2023 for English articles on ICIs and ADCs as systemic therapies (ICIs in first-line and adjuvant treatment for RCC, ICIs and ADCs in first- and second-line treatment for TCC). Randomised clinical trials were considered. The primary objective was overall survival (OS) of ICIs and ADCs between males and females. The secondary outcomes included progression-free survival, overall response rate, disease-free survival, and recurrence-free survival. Treatment efficacy was evaluated by sex via odds ratios (ORs) and confidence intervals compared with controls. Log ORs were used for creating a frequentist NMA. This meta-analysis was registered on PROSPERO (CRD42023468632). KEY FINDINGS AND LIMITATIONS: Eighteen articles met the inclusion criteria. Females had an advantage for RCC-adjuvant treatment for atezolizumab (log OR [SE] = -0.57 ± 0.25, p = 0.024) in OS. Males showed a survival advantage in TCC second-line treatment for ADC-Nectin 4 (log OR [SE] = 0.65 ± 0.28, p = 0.02). No other significant results were shown. CONCLUSIONS AND CLINICAL IMPLICATIONS: The NMA revealed gender-specific variations in ICI and ADC responses for RCC and TCC, offering insights for personalised cancer care and addressing disparities in cancer care and outcomes. PATIENT SUMMARY: In this systematic review, we looked at the sex differences for metastatic renal cell carcinoma (RCC) and transitional cell carcinoma (TCC) for antibody-drug conjugates and immune checkpoint inhibitors. In our analysis, female and male sex has better overall survival for adjuvant and second-line therapies for RCC and TCC, respectively. Urgent research on gender-specific cancer therapies is imperative.

Ablative Treatments for Small Renal Masses and Management of Recurrences: A Comprehensive Review.

This review focuses on ablative techniques for small renal masses (SRMs), including radiofrequency ablation (RFA), cryoablation (CA), microwave ablation (MWA), and irreversible electroporation (IRE), and discusses recurrence management. Through an extensive literature review, we outline the procedures, outcomes, and follow-up strategies associated with each ablative method. The review provides a detailed examination of these techniques-RFA, CA, MWA, and IRE-elucidating their respective outcomes. Recurrence rates vary among them, with RFA and CA showing comparable rates, MWA demonstrating favorable short-term results, and IRE exhibiting promise in experimental stages. For managing recurrences, various strategies are considered, including active surveillance, re-ablation, or salvage surgery. Surveillance is preferred post-RFA and post-CA, due to slow SRM growth, while re-ablation, particularly with RFA and CA, is deemed feasible without additional complications. Salvage surgery emerges as a viable option for larger or resistant tumors. While ablative techniques offer short-term results comparable to surgery, further research is essential to understand their long-term effects fully. Decisions concerning recurrence management should consider individual and tumor-specific factors. Imaging, notably contrast-enhanced ultrasounds, plays a pivotal role in assessing treatment success, emphasizing the necessity of a multidisciplinary approach for optimal outcomes. The lack of randomized trials highlights the need for further research.

Transurethral prostate surgery in prostate cancer patients: A population-based comparative analysis of complication and mortality rates.

Objective: Prostate cancer (PCa) patients might experience lower urinary tract symptoms as those diagnosed with benign prostatic hyperplasia (BPH). Some of them might be treated for their lower urinary tract symptoms instead of PCa. We aimed to test the effect of PCa versus BPH on surgical outcomes after transurethral prostate surgery, namely complication and mortality rates. Methods: Within the American College of Surgeons National Surgical Quality Improvement Program database (2011-2016), we identified patients who underwent transurethral resection of the prostate, photoselective vaporization, or laser enucleation. Patients were stratified according to postoperative diagnosis (PCa vs. BPH). Univariable and multivariable logistic regression models evaluated the predictors of perioperative morbidity and mortality. A formal test of interaction between diagnosis and surgical technique used was performed. Results: Overall, 34 542 patients were included. Of all, 2008 (5.8%) had a diagnosis of PCa. The multivariable logistic regression model failed to show statistically significant higher rates of postoperative complications in PCa patients (odds ratio: 0.9, 95% confidence interval: 0.7-1.1; p=0.252). Moreover, similar rates of perioperative mortality (p=0.255), major acute cardiovascular events (p=0.581), transfusions (p=0.933), and length of stay of more than or equal to 30 days (p=0.174) were found. Additionally, all tests failed to show an interaction between post-operative diagnosis and surgical technique used. Conclusion: Patients diagnosed with PCa do not experience higher perioperative morbidity or mortality after transurethral prostate surgery when compared to their BPH counterparts. Moreover, the diagnosis seems to not influence surgical technique outcomes.

Clinical Effects of Oral Supplementation of Gamma-Cyclodextrin Curcumin Complex in Male Patients with Moderate-To-Severe Benign Prostatic Hyperplasia-Related Lower Urinary Tract Symptoms.

INTRODUCTION: Benign prostatic hyperplasia (BPH) is the most common cause of lower urinary tract symptoms (LUTSs) in males. Curcumin exhibits anti-inflammatory and anti-tumor properties which may be effective for BPH. This multi-arm observational study evaluated the real-world efficacy of QURMIN® (Gamma-cyclodextrin-curcumin Complex-CAVACURMIN®) as single or combination therapy for BPH. METHODS: Men with moderate-severe LUTS/BPH, receiving a 6-month supplementation with QURMIN® alone or in combination with BPH-specific medication were propensity score matched with patients not taking curcumin and then divided into subgroups based on concomitant baseline treatment. Cohorts were compared in the 6-month variation of IPSS, quality of life (IPSS-QoL), Benign Prostatic Hyperplasia Impact Index (BII) and uroflowmetry parameters. Curcumin tolerability was evaluated in terms of discontinuations and adverse effects. RESULTS: The 1:1 propensity score matching resulted in a treatment-naïve (n = 152), an alpha-blocker only (AB) (n = 138) and AB + 5-alpha reductase inhibitors (5-ARIs) (n = 78) subgroup. After 6 months, drug-naïve patients taking curcumin reported significant improvement in IPSS-storage (-3.9, p < 0.001), IPSS-voiding (-2.0, p = 0.011), IPSS-total (-5.9, p < 0.001), IPSS-QoL (-3.9, p < 0.001), BII (-2.0, p < 0.001), Qmax (+3.1 mL/s, p < 0.001), Qmean (+1.9 mL/s, p = 0.005), post-void residual volume (-7.7 mL, p < 0.001), and PSA (-0.3 ng/mL, p = 0.003), compared to controls. Patients taking ABs and curcumin showed improvement in IPSS-storage (-2.7, p < 0.001), IPSS-voiding (-1.3, p = 0.033), IPSS-total (-3.5, p < 0.001), IPSS-QoL (-1.1, p = 0.004), BII (-1.7, p = 0.006), Qmax (+1.0 mL/s, p = 0.006), and PSA (-0.2 ng/mL, p = 0.01). Patients taking curcumin and AB + 5-ARI showed improvement in IPSS-storage (-1.3, p = 0.007), IPSS-total (-1.6, p = 0.034), IPSS-QoL (-1.1, p < 0.001), and BII (-2.0, p < 0.001). No adverse reactions were reported for curcumin supplementation. CONCLUSION: QURMIN® (CAVACURMIN®) led to significant improvements in symptom burden, uroflow parameters, and QoL, without significant additional side effects, thus proving to be a potential new treatment for BPH, either as a single therapy or in addition to standard treatment.

The Role of miRNA in Testicular Cancer: Current Insights and Future Perspectives.

Background and Objectives: Despite advancements in the diagnosis and treatment of testicular germ cell tumours (TGTCs), challenges persist in identifying reliable biomarkers for early detection and precise disease management. This narrative review addresses the role of microRNAs (miRNAs) as potential diagnostic tools and therapeutic targets in the treatment of TGCTs. Materials and Methods: Three databases (PubMed®, Web of Science™, and Scopus®) were queried for studies investigating the utility of miRNA as diagnostic tools, assessing their prognostic significance, and evaluating their potential to guide TGCT treatment. Different combinations of the following keywords were used, according to a free-text protocol: "miRNA", "non-coding RNA", "small RNA", "Testicular Cancer", "seminomatous testicular germ cell", "non-seminomatous testicular germ cell". Results: The potential of miRNAs as possible biomarkers for a non-invasive diagnosis of TGCT is appealing. Their integration into the diagnostic pathway for TGCT patients holds the potential to enhance the discriminative power of conventional serum tumour markers (STMs) and could expedite early diagnosis, given that miRNA overexpression was observed in 50% of GCNIS cases. Among miRNAs, miR-371a-3p stands out with the most promising evidence, suggesting its relevance in the primary diagnosis of TGCT, particularly when conventional STMs offer limited value. Indeed, it demonstrated high specificity (90-99%) and sensitivity (84-89%), with good positive predictive value (97.2%) and negative predictive value (82.7%). Furthermore, a direct relationship between miRNA concentration, disease burden, and treatment response exists, regardless of disease stages. The initial evidence of miRNA decrease in response to surgical treatment and systemic chemotherapy has been further supported by more recent results suggesting the potential utility of this tool not only in evaluating treatment response but also in monitoring residual disease and predicting disease relapse. Conclusions: MiRNAs could represent a reliable tool for accurate diagnosis and disease monitoring in the treatment of TGCT, providing more precise tools for early detection and treatment stratification. Nevertheless, well-designed clinical trials and comprehensive long-term data are needed to ensure their translation into effective clinical tools.

Neuraxial anesthesia versus general anesthesia in patients undergoing three-dimensional laparoscopic radical prostatectomy: Preliminary results of a prospective comparative study.

Objective: Neuraxial anesthesia (NA) showed to reduce both morbidity and mortality in patients undergoing laparoscopic surgery. We aimed to investigate the use of NA in patients undergoing transperitoneal three-dimensional laparoscopic radical prostatectomy (t-3DLRP) and compare the intraoperative and postoperative outcomes with a control group of patients undergoing t-3DLRP under general anesthesia (GA). Methods: A prospective, double-center, double-surgeon study cohort of 84 consecutive patients undergoing t-3DLRP between June 2019 and June 2021 was analyzed. A study group of 42 patients undergoing t-3DLRP under NA was compared with a control group of 42 patients undergoing t-3DLRP under GA. Results: The two group were similar in all demographic, clinical, and pathological variables. Postoperative blood gas parameters were within physiologic limits in both groups. Muscle relaxation was adequate for surgery during both NA and GA. Median length of stay was 1 day shorter for NA group than GA group (5 days vs. 6 days, p=0.05). t-3DLRP under NA had a statistically lower rate of minor complications (4.8% vs. 19.0%, p=0.03) and less postoperative pain (median numeric rating scale 3 vs. 4, p=0.01) compared to GA. No major complications were observed in both groups. Significantly more patients were willing to undergo a similar intervention under NA than GA (p=0.04). Conclusion: t-3DLRP under NA is a feasible and safe procedure, with less postoperative pain and fewer minor complications than the same procedure under GA. NA allows the maintenance of muscle relaxation and respiratory excursions without interfering with surgery.

Urinary MicroRNAs as Biomarkers of Urological Cancers: A Systematic Review.

MicroRNAs (miRNAs) are emerging as biomarkers for the detection and prognosis of cancers due to their inherent stability and resilience. To summarize the evidence regarding the role of urinary miRNAs (umiRNAs) in the detection, prognosis, and therapy of genitourinary cancers, we performed a systematic review of the most important scientific databases using the following keywords: (urinary miRNA) AND (prostate cancer); (urinary miRNA) AND (bladder cancer); (urinary miRNA) AND (renal cancer); (urinary miRNA) AND (testicular cancer); (urinary miRNA) AND (urothelial cancer). Of all, 1364 articles were screened. Only original studies in the English language on human specimens were considered for inclusion in our systematic review. Thus, a convenient sample of 60 original articles was identified. UmiRNAs are up- or downregulated in prostate cancer and may serve as potential non-invasive molecular biomarkers. Several umiRNAs have been identified as diagnostic biomarkers of urothelial carcinoma and bladder cancer (BC), allowing us to discriminate malignant from nonmalignant forms of hematuria. UmiRNAs could serve as therapeutic targets or recurrence markers of non-muscle-invasive BC and could predict the aggressivity and prognosis of muscle-invasive BC. In renal cell carcinoma, miRNAs have been identified as predictors of tumor detection, aggressiveness, and progression to metastasis. UmiRNAs could play an important role in the diagnosis, prognosis, and therapy of urological cancers.

Artificial intelligence and radiomics in evaluation of kidney lesions: a comprehensive literature review.

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.

A Novel Low-Cost Uroflowmetry for Patient Telemonitoring.

Uroflowmetry (UF) is a crucial guideline-recommended tool for men with benign prostatic obstruction (BPO). Moreover, UF is a helpful decision-making tool for the management of patients with lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH). In the last few years, telemedicine and telehealth have increased exponentially as cost-effective treatment options for both patients and physicians. Telemedicine and telehealth have been well positioned during the COVID-19 pandemic to prevent healthcare system overload and to ensure adequate management of patients through screening, diagnosis, and follow-up at home. In the present manuscript, the main characteristics and performance of a novel and low-cost device for home-based UF have been analyzed. The simple weight-transducer method has been applied to perform UF. An inexpensive load cell connected to a 24 bit analogic digital converter (ADC) sends data to a cloud server via SIM card or home Wi-Fi. Data are processed and shown in graphics with both volume and flow rate as a function of time, allowing for measurement of average flow rate, maximum flow rate, voided volume, and voiding time. A numerical algorithm allows for filtering of the dynamic effect due to the urine gravity acceleration and for removing the funnel to simplify the home measurement procedure. Through an online platform, the physician can see and compare each UF data. The device's reliability has been validated in a first laboratory setting and showed excellent performance. This approach based on domiciliary tests and an online platform can revolutionize the urologic clinic landscape by offering a constant patient cost-effective follow-up, eliminating the time wasted waiting in the office setting.

Robotic assisted simple prostatectomy versus other treatment modalities for large benign prostatic hyperplasia: a systematic review and meta-analysis of over 6500 cases.

BACKGROUND: Current guidelines recommend simple prostatectomy or endoscopic enucleation of the prostate (EEP) as treatment of choice for bladder prostatic obstruction (BPO) caused by large prostate glands. We aimed to provide a wide-ranging analysis of the currently available evidence, comparing safety and effectiveness of robot-assisted simple prostatectomy (RASP) versus open simple prostatectomy (OSP), laparoscopic simple prostatectomy (LSP), and laser EEP. METHODS: A systematic search was performed across MEDLINE, EMBASE, and Web of Science databases for retrospective and prospective studies comparing RASP to OSP or LSP or laser EEP (HoLEP/ThuLEP). Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) recommendations were followed to design the search strategies, selection criteria, and evidence report. A meta-analysis evaluated perioperative safety and effectiveness outcomes. The weighted mean difference and risk ratio were used to compare continuous and dichotomous variables, respectively. Quality was assessed using the Newcastle-Ottawa scale and the Cochrane Collaboration's tool for RCT article assessing risk of bias. RESULTS: 15 studies, including 6659 patients, were selected for meta-analysis: 13 observational studies, 1 non-randomized prospective study, and 1 randomized controlled trial. RASP was associated with statistically significant longer operative time (OT) and lower postoperative complication rate, length of stay (LOS), estimated blood loss (EBL), and transfusion rate (TR) compared to OSP. LSP showed longer LOS and lower postoperative SHIM score, with no difference in OT, EBL, and complications. Compared to laser EEP, RASP presented longer LOS and catheterization time and higher TR. ThuLEP presented shorter OT than RASP. No difference were found in functional outcomes between groups both subjectively (IPSS, QoL) and objectively (Qmax, PVR). CONCLUSION: RASP has become a size-independent treatment for the management of BPO caused by a large prostate gland. It can duplicate the functional outcomes of OSP while offering a better safety profile. When compared to LSP, the latter still stands as a valid lower-cost option, but it requires solid laparoscopic skill sets and therefore it is unlikely to spread on larger scale. When compared to laser EEP, RASP offers a shorter learning curve, but it still suffers from longer catheterization time and LOS.

Management of renal cell carcinoma in transplant kidney: a systematic review and meta-analysis.

INTRODUCTION: After transplantation, approximately 10% of renal cell carcinomas are detected in graft kidneys. These tumors (gRCC) present surgeons with the difficulty of finding a treatment that guarantees both oncological clearance and maintenance of function. We conducted a systematic review and an individual patient data meta-analysis on the oncology, safety and functional outcomes of the available treatments for gRCC. EVIDENCE ACQUISITION: A systematic search was performed across MEDLINE, EMBASE, and Web of Science including any study reporting perioperative, functional and survival outcomes for patients undergoing graft nephrectomy (GN), partial nephrectomy (PN) or thermal ablation (TA) for gRCC. Quade's ANCOVA, Spearman Rho and Pearson χ2, Kaplan-Meier, Log-rank and Standard Cox regression and other tests were used to compare treatments. Studies' quality was evaluated using a modified version of Newcastle Ottawa Scale. EVIDENCE SYNTHESIS: A number of 29 studies (357 patients) were included. No differences between TA and PN were found in terms of safety, functional and oncological outcomes for T1a gRCCs. When applied to pT1b gRCC, PN showed no difference in complications, progression or cancer-specific deaths compared to smaller lesions; PN validity for pT2 gRCCs should be considered unverified due to lack of sufficient evidence. The efficacy and safety of PN or TA for multiple gRCC remain controversial. In case of non-functioning, large (T≥2), complicated or metastatic gRCCs, GN appears to be the most reasonable choice. Quality of evidence ranged from very low to moderate. Studies with large cohorts and longer follow-up are still needed to clarify oncological and functional differences. CONCLUSIONS: PN and TA might be offered as a nephron-sparing treatment in patients with T1a gRCC. There is no significant difference between these options and GN in terms of oncological outcomes and complications. PN and TA offer similar functional outcomes and graft preservation. PN for T1b gRCC seems feasible and safe, but its validity should be considered unverified.

The anticancer effects of Metformin in the male germ tumor SEM-1 cell line are mediated by HMGA1.

Introduction: Germ cell tumors (GCTs) are the most common type of cancer in young men. These tumors usually originate from the testis, but they can occasionally develop from extragonadal sites probably due to primordial germ cells (PGCs) migration errors. Cisplatin-based chemotherapy is usually effective for male GCTs, but the risk of toxicity is high and new therapeutic strategies are needed. Although Metformin (Met) has been widely studied as a potential cancer treatment over the past decades, there is limited evidence to support its use in treating male GCTs. Additionally, the mechanism by which it acts on tumor cells is still not entirely understood. Methods: SEM-1 cells, a newly established human cell line of extragonadal origin, were treated with Met. Cell viability was studied by MTT assay, while cell migration and invasion were studied by the wound healing assay and the transwell assay, respectively. The effect of Met on 3D spheroid formation was determined by seeding SEM-1 cells in appropriate cell suspension culture conditions, and cell cycle was characterized by flow cytometry. Factors involved in PGCs migration and GCT invasion, such as IGFBP1, IGF1R, MMP-11 and c-Kit, together with cyclin D1 (a key regulator of cell cycle progression), and the upstream factor, HMGA1, were determined by immunoblots. Results: Treatment of SEM-1 cells with Met resulted in a potent and dose-dependent reduction of cell proliferation, as evidenced by decreased nuclear abundance of cyclin D1 and cell cycle arrest in G1 phase. Also, Met prevented the formation of 3D spheroids, and blocked cell migration and invasion by reducing the expression of IGFBP1, IGF1R and MMP-11. Both, IGFBP1 and MMP-11 are under control of HMGA1, a chromatin-associated protein that is involved in the regulation of important oncogenic, metabolic and embryological processes. Intriguingly, an early reduction in the nuclear abundance of HMGA1 occurred in SEM-1 cells treated with Met. Conclusions: Our results document the antiproliferative and antimigratory effects of Met in SEM-1 cells, providing new insights into the potential treatments for male GCTs. The anticancer properties of Met in SEM-1 cells are likely related to its ability to interfere with HMGA1 and downstream targets, including cyclin D1, the IGFs system, and MMP-11.

Changes in renal function after nephroureterectomy for upper urinary tract carcinoma: analysis of a large multicenter cohort (Radical Nephroureterectomy Outcomes (RaNeO) Research Consortium).

PURPOSE: To investigate prevalence and predictors of renal function variation in a multicenter cohort treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS: Patients from 17 tertiary centers were included. Renal function variation was evaluated at postoperative day (POD)-1, 6 and 12 months. Timepoints differences were Δ1 = POD-1 eGFR - baseline eGFR; Δ2 = 6 months eGFR - POD-1 eGFR; Δ3 = 12 months eGFR - 6 months eGFR. We defined POD-1 acute kidney injury (AKI) as an increase in serum creatinine by ≥ 0.3 mg/dl or a 1.5 1.9-fold from baseline. Additionally, a cutoff of 60 ml/min in eGFR was considered to define renal function decline at 6 and 12 months. Logistic regression (LR) and linear mixed (LM) models were used to evaluate the association between clinical factors and eGFR decline and their interaction with follow-up. RESULTS: A total of 576 were included, of these 409(71.0%) and 403(70.0%) had an eGFR < 60 ml/min at 6 and 12 months, respectively, and 239(41.5%) developed POD-1 AKI. In multivariable LR analysis, age (Odds Ratio, OR 1.05, p < 0.001), male gender (OR 0.44, p = 0.003), POD-1 AKI (OR 2.88, p < 0.001) and preoperative eGFR < 60 ml/min (OR 7.58, p < 0.001) were predictors of renal function decline at 6 months. Age (OR 1.06, p < 0.001), coronary artery disease (OR 2.68, p = 0.007), POD-1 AKI (OR 1.83, p = 0.02), and preoperative eGFR < 60 ml/min (OR 7.80, p < 0.001) were predictors of renal function decline at 12 months. In LM models, age (p = 0.019), hydronephrosis (p < 0.001), POD-1 AKI (p < 0.001) and pT-stage (p = 0.001) influenced renal function variation (ß 9.2 ± 0.7, p < 0.001) during follow-up. CONCLUSION: Age, preoperative eGFR and POD-1 AKI are independent predictors of 6 and 12 months renal function decline after RNU for UTUC.

Extent of lymph node dissection and impact on survival in radical cystectomy for advanced bladder cancer.

PURPOSE OF REVIEW: In patients with muscle invasive bladder cancer (MIBC) or unresectable non-MIBC, radical cystectomy is routinely combined with bilateral pelvic lymph node dissection (LND) owing to the oncological benefits found in recurrence-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS) compared with radical cystectomy alone. However, the optimal anatomic extent of LND is still unclear. RECENT FINDINGS: Retrospective studies were consistent in reporting oncological benefits of extended LND over nonextended LND. A recent RCT (the LEA trial) failed to demonstrate any benefit in terms of RFS, CSS and OS of super-extended LND over standard LND. Several confounding factors hindered the interpretation of the results, leaving the question of the right extent for LND still open. Results of a similar study, the SWOG S1011 are, therefore, highly anticipated. This study differed from the LEA study in several aspects but might also turn out to be a negative study. SUMMARY: There are still no firm data on the oncological benefit brought by more extended LND in patients with MIBC. Survival benefits seem limited, at least in the general population. Other factors could influence the impact of LND on survival, including the administration of adjuvant and neoadjuvant chemotherapies.

Current strategies to diagnose and manage positive surgical margins and local recurrence after partial nephrectomy.

Objective: No standard strategy for diagnosis and management of positive surgical margin (PSM) and local recurrence after partial nephrectomy (PN) are reported in literature. This review aims to provide an overview of the current strategies and further perspectives on this patient setting. Methods: A non-systematic review of the literature was completed. The research included the most updated articles (about the last 10 years). Results: Techniques for diagnosing PSMs during PN include intraoperative frozen section, imprinting cytology, and other specific tools. No clear evidence is reported about these methods. Regarding PSM management, active surveillance with a combination of imaging and laboratory evaluation is the first option line followed by surgery. Regarding local recurrence management, surgery is the primary curative approach when possible but it may be technically difficult due to anatomy resultant from previous PN. In this scenario, thermal ablation (TA) may have the potential to circumvent these limitations representing a less invasive alternative. Salvage surgery represents a valid option; six studies analyzed the outcomes of nephrectomy on local recurrence after PN with three of these focused on robotic approach. Overall, complication rates of salvage surgery are higher compared to TA but ablation presents a higher recurrence rate up to 25% of cases that can often be managed with repeat ablation. Conclusion: Controversy still exists surrounding the best strategy for management and diagnosis of patients with PSMs or local recurrence after PN. Active surveillance is likely to be the optimal first-line management option for most patients with PSMs. Ablation and salvage surgery both represent valid options in patients with local recurrence after PN. Conversely, salvage PN and radical nephrectomy have fewer recurrences but are associated with a higher complication rate compared to TA. In this scenario, robotic surgery plays an important role in improving salvage PN and radical nephrectomy outcomes.

Impact of extracorporeal shockwave therapy for erectile dysfunction and Peyronie's disease on reproductive and hormonal testicular function.

INTRODUCTION: Extracorporeal shock wave therapy is an established treatment for erectile dysfunction and Peyronie's disease. Concerns regarding the safety of extracorporeal shock wave therapy for andrological purposes on testicular function were raised by animal studies. AIM: To evaluate the impact of extracorporeal shock wave therapy for erectile dysfunction or Peyronie's disease on reproductive and hormonal testicular function. METHODS: We designed a prospective controlled study in which consecutive patients were enrolled. Males aged between 18 and 40 years with mild vasculogenic erectile dysfunction or acute inflammatory Peyronie's disease and normozoospermia were included. All enrolled patients were offered extracorporeal shock wave therapy, and subjects who refused extracorporeal shock wave therapy for any reason were considered as the Control group. All patients in the Intervention group were treated with DUOLITH SD1 T-TOP by a single expert urologist. Semen analysis and serum total testosterone dosage were performed before the start (T0) and 3 months after the end of extracorporeal shock wave therapy (T1) in Intervention group. The same parameters were evaluated after the extracorporeal shock wave therapy refusal (T0) and at the end of the following 3 months (T1) in Control group. Normozoospermia was chosen as the primary outcome, serum total testosterone concentration was selected as the secondary outcome. RESULTS: A total of 94 patients were enrolled in the study (48 Group A, 46 Group B). At T0, all patients were normozoospermic in both groups (p = 0.563), and no significant difference in mean ± SD total testosterone levels was recorded between the groups (582.5 ± 107.2 vs. 634.6 ± 108.4 ng/dl; p = 0.221). At T1, no significant deterioration (p > 0.05) in semen parameters was recorded in both groups. Only a statistically significant reduction in seminal pH was found after extracorporeal shock wave therapy compared to baseline (7.9 ± 0.3 vs. 7.5 ± 0.2; p < 0.001) and untreated patients (7.8 ± 0.2 vs. 7.5 ± 0.2; p < 0.001). No significant difference in total testosterone levels was recorded in Intervention group after extracorporeal shock wave therapy compared to baseline (p = 0.584). CONCLUSION: Extracorporeal shock wave therapy in erectile dysfunction and Peyronie's disease patients does not seem to affect reproductive and hormonal testicular function.

Impact of Surgery for Benign Prostatic Hyperplasia on Sexual Function: A Systematic Review and Meta-analysis of Erectile Function and Ejaculatory Function.

CONTEXT: Several sexual side effects, including erectile, ejaculatory, and orgasmic dysfunction, were reported with the majority of surgical procedures for benign prostatic obstruction (BPO). OBJECTIVE: To systematically review current evidence regarding the impact of benign prostatic hyperplasia (BPH) surgery on sexual function. EVIDENCE ACQUISITION: A comprehensive bibliographic search on the MEDLINE, Cochrane Library, Embase, Web of Science, and Google Scholar databases was conducted in July 2021. The population, intervention, comparator, and outcome (PICO) model was used to define study eligibility. Studies were Included if they assessed patients with BPO and related lower urinary tract symptoms (P) undergoing BPH surgery (I) with or without a comparison between surgical treatments (C) evaluating the impact on sexual function (O). Retrospective and prospective primary studies were included. A pooled analysis was conducted on studies including the postoperative assessment of International Index of Erectile Function (IIEF)-5, Male Sexual Health Questionnaire-Ejaculatory Dysfunction (MSHQ-EjD; Function and/or Bother), or retrograde ejaculation (RE) rate (PROSPERO database ID: CRD42020177907). EVIDENCE SYNTHESIS: A total of 151 studies investigating 20 531 patients were included. Forty-eight randomized controlled trials evaluating 5045 individuals were eligible for the meta-analysis. In most studies (122, 80.8%), only erectile and/or ejaculatory function was evaluated. A substantial number of articles (67, 44.4%) also used nonvalidated tools to evaluate erectile and/or ejaculatory function. The pooled analysis showed no statistically significant changes in IIEF-5 score compared with baseline for the transurethral resection of the prostate (TURP; weighted mean difference [WMD] 0.76 pts; 95% confidence interval [CI] -0.1, 1.62; p = 0.08), laser procedure (WMD 0.33 pts; 95% CI -0.1, 0.77; p = 0.13), and minimally invasive treatment (WMD -1.37 pts; 95% CI -3.19, 0.44; p = 0.14) groups. A statistically significantly higher rate of RE was found after TURP (risk ratio [RR] 13.31; 95% CI 8.37, 21.17; p < 0.00001), other electrosurgical procedures (RR 34.77; 95% CI 10.58, 127.82; p < 0.00001), and the entire laser group (RR 17.37; 95% CI 5.93, 50.81; p < 0.00001). No statistically significant increase in RE rate was described after most of the minimally invasive procedures (p > 0.05). The pooled analysis of MSHQ-EjD scores was possible only for prostatic urethral lift, showing no statistically significant difference between baseline and post-treatment MSHQ-EjD Function scores (WMD -0.80 pts; 95% CI -2.41, 0.81; p = 0.33), but postoperative MSHQ-EjD Bother scores were significantly higher (WMD 0.76 pts; 95% CI 0.22, 1.30; p = 0.006). CONCLUSIONS: Erectile function appears to be unaffected by most surgical procedures for BPO. RE is a very common adverse event of BPH surgery, although emerging minimally invasive surgical procedures could be associated with a lower risk. PATIENT SUMMARY: Benign prostatic hyperplasia surgery can have an impact on sexual function, mainly involving ejaculatory function.