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Background and objective: More than 10% of patients with negative clinical metastatic status (cN0M0) on conventional imaging for prostate cancer (PCa) harbor lymph node involvement (pN+) at final pathology following radical prostatectomy (RP) and lymphadenectomy. Our aim was to assess outcomes of initial observation for cN0M0 pN+ PCa and identify prognostic factors that may help in clinical decision-making. Methods: We performed a retrospective multicenter study of patients with cN0M0 PCa on conventional imaging (computed tomography and/or magnetic resonance imaging, and a bone scan) who were found to have pN+ disease at RP between 2000 and 2021. Biochemical recurrence (BCR) and systemic progression/recurrence were the primary outcomes. Kaplan-Meier curves and Cox proportional hazards model were used for survival and multivariate analysis. Key findings and limitations: A total of 469 men were included in this retrospective multicenter trial. Median prostate-specific antigen (PSA) was 10.1 ng/ml (interquartile range [IQR] 6.6–18.0). Among these patients, 56% had grade group ≥4, 53.7% had stage ≥pT3b, 42.6% had positive margins, and 19.6% had PSA persistence. The median number of positive nodes and of nodes removed were 1 (IQR 1–3) and 20 (14–28), respectively. At median follow-up of 41 mo, 48.5% experienced BCR. The 5-yr BCR-free survival rate was 31.7% (95% confidence interval [CI] 26.33–37.1%). Salvage treatments were needed in 211 patients and included radiotherapy (RT; n = 53), RT + androgen deprivation therapy (ADT; n = 88), ADT alone (n = 68), and salvage lymphadenectomy (n = 2). The 5-yr estimated survival rates were 66.3% (95% CI 60.4–72.1) for metastasis-free survival, 97.7% (95% CI 95.5–99.8%) for cancer-specific survival, and 95.3% (95% CI 92.4–98.1%) for overall survival. On multivariable analysis, PSA persistence was an independent predictor of BCR (odds ratio [OR] 51.8, 95% CI 12.2–219.2), exit from observation (OR 8.5, 95% CI 4.4–16.5), and systemic progression (OR 3.0, 95% CI 1.771–4.971). Conclusions: Initial observation in the management of pN+ cN0M0 PCa is feasible and has excellent survival rates in the intermediate term. Patients with worse disease features, especially PSA persistence, have a higher likelihood of recurrence and progression and may be candidates for more aggressive upfront management. Patient summary: We investigated the value of initial observation for men with prostate cancer with negative scan findings for metastasis who were then found to have positive lymph nodes after surgery to remove the prostate. Our results show that initial observation is a good option for patients with less aggressive prostate cancer features.

Background and objective: The treatment landscape of metastatic prostate cancer (mPCa) has evolved significantly over the past two decades. Despite this, the optimal therapy for patients with mPCa has not been determined. This systematic review identifies available predictive models that assess mPCa patients’ response to treatment. Methods: We critically reviewed MEDLINE and CENTRAL in December 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Only quantitative studies in English were included with no time restrictions. The quality of the included studies was assessed using the PROBAST tool. Data were extracted following the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews criteria. Key findings and limitations: The search identified 616 citations, of which 15 studies were included in our review. Nine of the included studies were validated internally or externally. Only one study had a low risk of bias and a low risk concerning applicability. Many studies failed to detail model performance adequately, resulting in a high risk of bias. Where reported, the models indicated good or excellent performance. Conclusions and clinical implications: Most of the identified predictive models require additional evaluation and validation in properly designed studies before these can be implemented in clinical practice to assist with treatment decision-making for men with mPCa. Patient summary: In this review, we evaluate studies that predict which treatments will work best for which metastatic prostate cancer patients. We found that existing studies need further improvement before these can be used by health care professionals.

Combination therapies in metastatic hormone-sensitive prostate cancer (mHSPC), which include the addition of an androgen receptor signaling inhibitor and/or docetaxel to androgen deprivation therapy, have been a game changer in the management of this disease stage. However, these therapies come with their fair share of toxicities and side effects. The goal of this observational study is to report drug-related adverse events (AEs), which are correlated with systemic combination therapies for mHSPC. Determining the optimal treatment option requires large cohorts to estimate the tolerability and AEs of these combination therapies in “real-life” patients with mHSPC, as provided in this study. We use a network of databases that includes population-based registries, electronic health records, and insurance claims, containing the overall target population and subgroups of patients defined by unique certain characteristics, demographics, and comorbidities, to compute the incidence of common AEs associated with systemic therapies in the setting of mHSPC. These data sources are standardised using the Observational Medical Outcomes Partnership Common Data Model. We perform the descriptive statistics as well as calculate the AE incidence rate separately for each treatment group, stratified by age groups and index year. The time until the first event is estimated using the Kaplan-Meier method within each age group. In the case of episodic events, the anticipated mean cumulative counts of events are calculated. Our study will allow clinicians to tailor optimal therapies for mHSPC patients, and they will serve as a basis for comparative method studies.

Objective: To report a case of robot-assisted partial nephrectomy (RAPN) for two highly complex renal tumors in a patient with a Horseshoe kidney (HSK), focusing on the utility of hyperaccuracy three-dimensional (HA3D) virtual models for accurate preoperative and intraoperative planning of the procedure.Methods: A 74-year-old Caucasian male patient was referred to our Unit for incidental detection of two complex renal masses in the left portion of a HSK. The 50 × 55 mm, larger, predominantly exophytic renal mass was located at the middle-lower pole of the left-sided kidney (PADUA score 9). The 16 × 17 mm, smaller, hilar renal mass was located at the middle-higher pole of the left-sided kidney (PADUA score 9). Contrast-enhanced CT scan images in DICOM format were processed using a dedicated software to achieve a HA3D virtual reconstructions. RAPN was performed by a highly experienced surgeon using the da Vinci Si robotic platform with a three-arm configuration. A selective delayed clamping strategy was adopted for resection of the larger renal mass while a clampless strategy was adopted for the smaller renal mass. An enucleative resection strategy was pursued for both tumors.Results: The overall operative time was 150 min, with a warm ischemia time of 21 min. No intraoperative or postoperative complications were recorded. Final resection technique according to the SIB score was pure enucleation for both masses. At histopathological analysis, both renal masses were clear cell renal cell carcinoma (ccRCC) (stage pT1bNxMx and pT3aNxMx for the larger and smaller mass, respectively). At a follow-up of 7 months, there was no evidence of local or systemic recurrence.Conclusions: Surgical management of complex renal masses in patients with HSKs is challenging and decision-making is highly nuanced. To optimize postoperative outcomes, proper surgical experience and careful preoperative planning are key. In this regard, 3D models can play a crucial role to refine patient counseling, surgical decision-making, and pre- and intraoperative planning during RAPN, tailoring surgical strategies and techniques according to the single patient's anatomy.

Simple Summary: The choice between a transrectal or a transperineal approach for MRI-fusion-targeted prostate biopsy is still the subject of debate within the urologic community and across international Guidelines. Specifically, the European Association of Urology (EAU) guidelines recommend abandoning TRPB in favor of TPPB, due to lower rates of infection and sepsis. In contrast, the American Urological Association (AUA) recommends either approach, citing the absence of prospective RCTs assessing infectious risk. In this scenario, transparent reporting of the morbidity of the transrectal prostate biopsy is crucial to inform patients during shared decision-making and to evaluate the cost-effectiveness of different biopsy approaches from clinical and economic standpoints. Despite transrectal prostate biopsy (TRPB) being still widespread globally, the EAU Guidelines strongly recommend the transperineal approach, due to the reported lower infectious risk. Our study aims to evaluate the impact of a standardized clinical pathway for TRPB on post-operative complications. We prospectively collected data from all patients undergoing mpMRI-targeted TRPB at our Academic Centre from January 2020 to December 2022. All patients followed a standardized, structured multistep pathway. Post-procedural complications were collected and classified according to the Clavien–Dindo (CD) Classification. Among 458 patients, post-procedural adverse events were reported by 203 (44.3%), of which 161 (35.2%) experienced CD grade 1 complications (hematuria [124, 27.1%], hematochezia [22, 4.8%], hematospermia [14, 3.1%], or a combination [20, 4.4%]), and 45 (9.0%) reported CD grade 2 complications (acute urinary retention or hematuria needing catheterization, as well as urinary tract infections, of which 2 cases required hospitalization). No major complications, including sepsis, were observed. At uni- and multivariable analysis, age > 70 years and BMI > 25 kg/ m2 for patients were identified as predictors of post-operative complications. The results of our study confirm that TRPB is a safe and cost-effective procedure with a low risk of severe adverse events in experienced hands and following a standardized pathway. [ABSTRACT FROM AUTHOR]

Purpose: To learn about the history and development of en bloc resection of bladder tumour (ERBT), and to discuss its future directions in managing bladder cancer. Methods: In this narrative review, we summarised the history and early development of ERBT, previous attempts in overcoming the tumour size limitation, consolidative effort in standardising the ERBT procedure, emerging evidence in ERBT, evolving concepts in treating large bladder tumours, and the future directions of ERBT. Results: Since the first report on ERBT in 1980, there has been tremendous advancement in terms of its technique, energy modalities and tumour retrieval methods. In 2020, the international consensus statement on ERBT has been developed and it serves as a standard reference for urologists to practise ERBT. Recently, high-quality evidence on ERBT has been emerging. Of note, the EB-StaR study showed that ERBT led to a reduction in 1-year recurrence rate from 38.1 to 28.5%. An individual patient data meta-analysis is currently underway, and it will be instrumental in defining the true value of ERBT in treating non-muscle-invasive bladder cancer. For large bladder tumours, modified approaches of ERBT should be accepted, as the quality of resection is more important than a mere removal of tumour in one piece. The global ERBT registry has been launched to study the value of ERBT in a real-world setting. Conclusion: ERBT is a promising surgical technique in treating bladder cancer and it has gained increasing interest globally. It is about time for us to embrace this technique in our clinical practice. [ABSTRACT FROM AUTHOR]

Background: The aim of our study is to evaluate the prevalence and predictive factors of short- (30 d) and mid-term continence in a contemporary cohort of patients treated with robotic-assisted laparoscopic prostatectomy (RALP) without any posterior or anterior reconstruction at our referral academic center. Methods: Data from patients undergoing RALP between January 2017 and March 2021 were prospectively collected. RALP was performed by three highly experienced surgeons following the principles of the Montsouris technique, with a bladder-neck-sparing intent and maximal preservation of the membranous urethra (if oncologically safe) without any anterior/posterior reconstruction. (Self-assessed urinary incontinence (UI) was defined as the need of one or more pads per die (excluding the need for a safety pad/die. Univariable and multivariable logistic regression analysis was used to assess the independent predictors of early incontinence among routinely collected patient- and tumor-related variables). Results: A total of 925 patients were included; of these, 353 underwent RALP (38.2%) without nerve-sparing intent. The median patient age and BMI were 68 years (IQR 63–72) and 26 (IQR 24.0–28.0), respectively. Overall, 159 patients (17.2%) reported early (30 d) incontinence. In multivariable analysis adjusting for patient- and tumor-related features, a non-nerve-sparing procedure (OR: 1.57 [95% CI: 1.03–2.59], p = 0.035) was independently associated with the risk of urinary incontinence in the short-term period, while the absence of cardiovascular diseases before surgery (OR: 0.46 [95% CI: 0.320.67], p ≤ 0.01) was a protective factor for this outcome. At a median follow-up of 17 months (IQR 10–24), 94.5% of patients reported to be continent. Conclusions: In experienced hands, most patients fully recover urinary continence after RALP at mid-term follow-up. On the contrary, the proportion of patients who reported early incontinence in our series was modest but not negligible. The implementation of surgical techniques advocating anterior and/or posterior fascial reconstruction might improve the early continence rate in candidates for RALP. [ABSTRACT FROM AUTHOR]

Simple Summary: The association between inflammation and cancer is well demonstrated. The aim of our study was to investigate the topographic and quantitative association between inflammation, proliferative inflammatory atrophy and Prostate Cancer (PCa) in frustules from prostate biopsies. We demonstrated an association between prostate inflammation (PI) and PCa in tissue from prostate biopsies, confirming the basis of future research aimed at evaluating anti-inflammatory therapies as a way to prevent PCa. Background: Extensive research effort has been devoted to investigating the link between inflammation and PCa. However, this relationship remains unclear and controversial. The aim of our multi-center study was to investigate this association by histologically evaluating the distribution of PI and PCA in prostate biopsy cores from patients of eight referral centers in Italy. Results: We evaluated 2220 cores from 197 patients; all the frustules were re-evaluated by dedicated pathologists retrospectively. Pathologists assigned IRANI scores and determined the positions of PIs; pathologists also re-evaluated the presence of PCa and relative ISUP grade. PCa was recorded in 749/2220 (33.7%). We divided this sample into a PCa PI group (634/749 cores [84.7%]) and a non-PCa + PI group (1157/1471 cores [78.7%]). We observed a statistically significant difference in the presence of inflammation among cores with cancer (p < 0.01). Moreover, periglandular inflammation was higher in the cores with neoplasia, while stromal inflammation was higher in cores without neoplasia (38.5% vs. 31.1% and 55.4% vs. 63.5% p < 0.01). Conclusions: In our experience, there is evidence of an association between PI and PCa at a tissue level. Further studies are needed to confirm our findings and to identify patients who might benefit from target therapies to prevent PCa occurrence and/or progression. [ABSTRACT FROM AUTHOR]

Background: There is evidence that, after severe acute respiratory syndrome coronavirus 2 infection, male reproductive function and semen quality may be damaged Objectives: To evaluate a panel of inflammatory mediators in semen in patients recovered from coronavirus disease 2019. Material and methods: Sexually active men with previous severe acute respiratory syndrome coronavirus 2 infection and proven recovery from coronavirus disease 2019 were enrolled in a prospective cohort study. Clinical, uro‐andrological data and semen specimens were prospectively collected. For previously hospitalized coronavirus disease 2019 patients, data on serum inflammatory markers were retrospectively collected. Results: A total of 43 men were enrolled in the study. Of these, 32 men were normozoospermic, three were oligozoospermic, and eight were crypto‐azoospermic. Serum inflammatory markers (procalcitonin and C‐reactive protein) were analyzed in previously hospitalized patients both at admission and at peak of infection. Levels at admission were statistically significantly higher in patients resulting in crypto‐azoospermic with respect to those resulting in normozoospermic (p = 0.05; p = 0.03 and p = 0.02, respectively) after healing. Seminal cytokine levels were similar among all groups. Interleukin‐1β and tumor necrosis factor‐α levels were significantly negatively related to sperm total number and concentration, whereas interleukin‐4 was correlated with sperm motility. Discussion and conclusion: Negative correlations between interleukin‐1β and tumor necrosis factor‐α and sperm number and the overall high levels of semen cytokines indicate a potential detrimental role of severe acute respiratory syndrome coronavirus 2 driven inflammation on spermatogenesis. Overall, our results indicate that male patients recovering from coronavirus disease 2019 deserve accurate follow‐up for their fertility status. [ABSTRACT FROM AUTHOR]

With the introduction of EU citizenship a set of colliding and overlapping political frames and rights constellations has established new forms of mobility across EU member states. In this regard, respective scholarship has focused particularly on the reach and limits of EU citizenship status and rights. Yet, less attention has been paid to the question of how mobile EU citizens themselves experience these citizenship constellations when they settle into another EU member state. Addressing this question empirically, the article compares EU mobiles' experiences in two European capital cities, Berlin and Copenhagen. It applies a mixed-method design drawing from data of an online questionnaire and, especially, semi-structured interviews with EU mobiles. A particular focus is put on EU mobiles' ability to navigate local and national regulations through which EU citizenship is orchestrated. Their experiences shed light on how membership becomes situational and dependent on local and national regulations and contexts, while EU citizenship status and rights are considered less relevant. Against this background, the findings emphasise how bottom-up perspectives to citizenship complement more dominant perspectives in the literature which focus mainly on rights, legal status and political frameworks from the top down. [ABSTRACT FROM AUTHOR]