Efficacy and safety of antegrade sclerotherapy for varicocele in pediatric patients: A systematic review.

OBJECTIVES: Antegrade sclerotherapy (Tauber's) procedure has been extensively used for the minimally-invasive treatment of varicocele; however, the results in the pediatric population are less defined. This systematic review evaluates the efficacy and safety of antegrade sclerotherapy for varicocele in the pediatric population. EVIDENCE ACQUISITION: The review was conducted following the PRISMA guidelines. Systematic research of available literature in English language from 1980 until May 2022 was conducted through EMBASE, MEDLINE, Cochrane Library, and NIH Registry of Clinical Trials. For each study, information was gathered regarding the study design, the inclusion/exclusion criteria, the indications for treatment, the success rate and the complications. When available, the details about sperm analysis were reported. EVIDENCE SYNTHESIS: The 10 studies were included in the final sample (564 patients). Median age of patients ranged 13.3-15.3 years. The indications for scleroembolization varied in the different studies, while most studies included patients with clinical G2-G3 varicocele and clinical symptoms or testicular asymmetry. The treatment was successful in 88%-98% of the patients, while the complication rate was <5%. CONCLUSION: Tauber's sclerotherapy is a safe and effective treatment for varicocele also in the pediatric population. Further studies with standardized inclusion criteria are needed to provide higher level of evidence and compare the outcomes of antegrade sclerotherapy with the other available techniques.

Navigating the evolving diagnostic and therapeutic landscape of low- and intermediate-risk prostate cancer.

ABSTRACT: In this nonsystematic review of the literature, we explored the changing landscape of detection and treatment of low- and intermediate-risk prostate cancer (PCa). Through emphasizing improved cancer assessment with histology classification and genomics, we investigated key developments in PCa detection and risk stratification. The pivotal role of prostate magnetic resonance imaging (MRI) in the novel diagnostic pathway is examined, alongside the benefits and drawbacks of MRI-targeted biopsies for detection and tumor characterization. We also delved into treatment options, particularly active surveillance for intermediate-risk PCa. Outcomes are compared between intermediate- and low-risk patients, offering insights into tailored management. Surgical techniques, including Retzius-sparing surgery, precision prostatectomy, and partial prostatectomy for anterior cancer, are appraised. Each technique has the potential to enhance outcomes and minimize complications. Advancements in technology and radiobiology, including computed tomography (CT)/MRI imaging and positron emission tomography (PET) fusion, allow for precise dose adjustment and daily target monitoring with imaging-guided radiotherapy, opening new ways of tailoring patients' treatments. Finally, experimental therapeutic approaches such as focal therapy open new treatment frontiers, although they create new needs in tumor identification and tracking during and after the procedure.

An updated model for predicting side-specific extraprostatic extension in the era of MRI-targeted biopsy.

PURPOSE: Accurate prediction of extraprostatic extension (EPE) is pivotal for surgical planning. Herein, we aimed to provide an updated model for predicting EPE among patients diagnosed with MRI-targeted biopsy. MATERIALS AND METHODS: We analyzed a multi-institutional dataset of men with clinically localized prostate cancer diagnosed by MRI-targeted biopsy and subsequently underwent prostatectomy. To develop a side-specific predictive model, we considered the prostatic lobes separately. A multivariable logistic regression analysis was fitted to predict side-specific EPE. The decision curve analysis was used to evaluate the net clinical benefit. Finally, a regression tree was employed to identify three risk categories to assist urologists in selecting candidates for nerve-sparing, incremental nerve sparing and non-nerve-sparing surgery. RESULTS: Overall, data from 3169 hemi-prostates were considered, after the exclusion of prostatic lobes with no biopsy-documented tumor. EPE was present on final pathology in 1,094 (34%) cases. Among these, MRI was able to predict EPE correctly in 568 (52%) cases. A model including PSA, maximum diameter of the index lesion, presence of EPE on MRI, highest ISUP grade in the ipsilateral hemi-prostate, and percentage of positive cores in the ipsilateral hemi-prostate achieved an AUC of 81% after internal validation. Overall, 566, 577, and 2,026 observations fell in the low-, intermediate- and high-risk groups for EPE, as identified by the regression tree. The EPE rate across the groups was: 5.1%, 14.9%, and 48% for the low-, intermediate- and high-risk group, respectively. CONCLUSION: In this study we present an update of the first side-specific MRI-based nomogram for the prediction of extraprostatic extension together with updated risk categories to help clinicians in deciding on the best approach to nerve-preservation.

European Association of Urology Biochemical Recurrence Risk Classification as a Decision Tool for Salvage Radiotherapy-A Multicenter Study.

BACKGROUND: The European Association of Urology (EAU) has proposed a risk stratification for patients harboring biochemical recurrence (BCR) after radical prostatectomy (RP). OBJECTIVE: To assess whether this risk stratification helps in choosing patients for salvage radiotherapy (SRT). DESIGN, SETTING, AND PARTICIPANTS: Analyses of 2379 patients who developed BCR after RP (1989-2020), within ten European high-volume centers, were conducted. Early and late SRT were defined as SRT delivered at prostate-specific antigen values <0.5 and ≥0.5 ng/ml, respectively. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable Cox models tested the effect of SRT versus no SRT on death and cancer-specific death. The Simon-Makuch method tested for survival differences within each risk group. RESULTS AND LIMITATIONS: Overall, 805 and 1574 patients were classified as having EAU low- and high-risk BCR. The median follow-up was 54 mo after BCR for survivors. For low-risk BCR, 12-yr overall survival was 87% versus 78% (p = 0.2) and cancer-specific survival was 100% versus 96% (p = 0.2) for early versus no SRT. For high-risk BCR, 12-yr overall survival was 81% versus 66% (p < 0.001) and cancer-specific survival was 98% versus 82% (p < 0.001) for early versus no SRT. In multivariable analyses, early SRT decreased the risk for death (hazard ratio [HR]: 0.55, p < 0.01) and cancer-specific death (HR: 0.08, p < 0.001). Late SRT was a predictor of cancer-specific death (HR: 0.17, p < 0.01) but not death (p = 0.1). CONCLUSIONS: Improved survival was recorded within the high-risk BCR group for patients treated with early SRT compared with those under observation. Our results suggest recommending early SRT for high-risk BCR men. Conversely, surveillance might be suitable for low-risk BCR, since only nine patients with low-risk BCR died from prostate cancer during follow-up. PATIENT SUMMARY: The impact of salvage radiotherapy (SRT) on cancer-specific outcomes stratified according to the European Association of Urology biochemical recurrence (BCR) risk classification was assessed. While men with high-risk BCR should be offered SRT, surveillance might be a suitable option for those with low-risk BCR.

Which Patients with Prostate Cancer and Lymph Node Uptake at Preoperative Prostate-specific Membrane Antigen Positron Emission Tomography/Computerized Tomography Scan Are at a Higher Risk of Prostate-specific Antigen Persistence After Radical Prostatectomy? Identifying Indicators of Systemic Disease by Integrating Clinical, Magnetic Resonance Imaging, and Functional Imaging Parameters.

BACKGROUND: The role of local therapies including radical prostatectomy (RP) in prostate cancer (PCa) patients with clinical lymphadenopathies on prostate-specific membrane antigen (PSMA) positron emission tomography/computerized tomography (PET/CT) has scarcely been explored. Limited data are available to identify men who would benefit from RP; on the contrary, those more likely to benefit already have systemic disease. OBJECTIVE: We aimed to assess the predictors of prostate-specific antigen (PSA) persistence in surgically managed PCa patients with lymphadenopathies on a PSMA PET/CT scan by integrating clinical, magnetic resonance imaging (MRI), and PSMA PET/CT parameters. DESIGN, SETTING, AND PARTICIPANTS: We identified 519 patients treated with RP and extended lymph node dissection, and who received preoperative PSMA PET between 2017 and 2022 in nine referral centers. Among them, we selected 88 patients with nodal uptake at preoperative PSMA PET (miTxN1M0). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The outcome was PSA persistence, defined as a PSA value of ≥0.1 ng/ml at the first measurement after surgery. Multivariable logistic regression models tested the predictors of PSA persistence. Covariates consisted of biopsy International Society of Urological Pathology (ISUP) grade group, clinical stage at MRI, and number of positive spots at a PET/CT scan. A regression tree analysis stratified patients into risk groups based on preoperative characteristics. RESULTS AND LIMITATIONS: Overall, lymph node invasion (LNI) was detected in 63 patients (72%) and 32 (36%) experienced PSA persistence after RP. At multivariable analyses, having more than two lymph nodal positive findings at PSMA PET, seminal vesicle invasion (SVI) at MRI, and ISUP grade group >3 at biopsy were independent predictors of PSA persistence (all p < 0.05). At the regression tree analysis, patients were stratified in four risk groups according to biopsy ISUP grade, number of positive findings at PET/CT, and clinical stage at MRI. The model depicted good discrimination at internal validation (area under the curve 78%). CONCLUSIONS: One out of three miN1M0 patients showed PSA persistence after surgery. Patients with ISUP grade 2-3, as well as patients with organ-confined disease at MRI and a single or two positive nodal findings at PET are those in whom RP may achieve the best oncological outcomes in the context of a multimodal approach. Conversely, patients with a high ISUP grade and extracapsular extension or SVI or more than two spots at PSMA PET should be considered as potentially affected by systemic disease upfront. PATIENT SUMMARY: Our novel and straightforward risk classification integrates currently available preoperative risk tools and should, therefore, assist physician in preoperative counseling of men candidates for radical treatment for prostate cancer with positive lymph node uptake at prostate-specific membrane antigen positron emission tomography.

Role of targeted biopsy, perilesional biopsy, random biopsy, and their combination in the detection of clinically significant prostate cancer by mpMRI/transrectal ultrasonography fusion biopsy in confirmatory biopsy during active surveillance program.

BACKGROUND: Based on the findings of different trials in biopsy naïve patients, target biopsy (TB) plus random biopsy (RB) during mpMRI-guided transrectal ultrasound fusion biopsy (FB) are often also adopted for the biopsy performed during active surveillance (AS) programs. At the moment, a clear consensus on the extent and modalities of the procedure is lacking. OBJECTIVE: To evaluate the increase in diagnostic accuracy achieved by perilesional biopsy (PL) and different RB schemes during FB performed in AS protocol. DESIGN, SETTING, AND PARTICIPANTS: We collected prospectively the data of 112 consecutive patients with low- or very-low-risk prostate cancer; positive mpMRI underwent biopsy at a single academic institution in the context of an AS protocol. INTERVENTION(S): mpMRI/transrectal US FB with Hitachi RVS system with 3 TB and concurrent transrectal 24-core RB. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The diagnostic yield of the different possible biopsy schemes (TB only; TB + 4 perilesional (PL) cores; TB + 12-core RB; TB + 24-core RB) was compared by the McNemar test. Univariable and multivariable regression analyses were adopted to identify predictors of any cancer, Gleason grade group (GGG) ≥2 cancers, and the presence of GGG≥2 cancers in the larger schemes only. RESULTS AND LIMITATIONS: The detection rate of GGG ≥2 cancers increased to 30%, 39%, and 49% by adding 4 PL cores, 14, and 24 RB cores, respectively, to TB cores (all p values <0.01). On the whole, TB alone, 14-core RB, and 24-core-RB identified 38%, 47%, and 56% of all the GGG ≥2 cancers. Such figures increased to 62% by adding to TB 4 PL cores, and to 80% by adding 14 RB cores. Most of the differences were observed in PI-RADS 4 lesions. CONCLUSIONS: We found that PL biopsy increased the detection rate of GGG ≥2 cancers as compared with TB alone. However, the combination of those cores missed a large percentage of the CS cancers identified with larger RB cores, including a 20% of CS cancers diagnosed only by the combination of TB plus 24-core RB.

The Prognostic Role of Preoperative PSMA PET/CT in cN0M0 pN+ Prostate Cancer: A Multicenter Study.

CONTEXT: Despite negative preoperative conventional imaging, up to 10% of patients with prostate cancer (PCa) harbor lymph-node involvement (LNI) at radical prostatectomy (RP). The advent of more accurate imaging modalities such as PET/CT improved the detection of LNI. However, their clinical impact and prognostic value are still unclear. We aimed to investigate the prognostic value of preoperative PET/CT in patients node positive (pN+) at RP. EVIDENCE SYNTHESIS: We retrospectively identified cN0M0 patients at conventional imaging (CT and/or MRI, and bone scan) who had pN+ PCa at RP at 17 referral centers. Patients with cN+ at PSMA/Choline PET/CT but cN0M0 at conventional imaging were also included. Systemic progression/recurrence was the primary outcome; Cox proportional hazards models were used for multivariate analysis. EVIDENCE ACQUISITION: We included 1163 pN+ men out of whom 95 and 100 had preoperative PSMA and/or Choline PET/CT, respectively. ISUP grade ≥4 was detected in 66.6%. Overall, 42% of patients had postoperative PSA persistence (≥0.1 ng/mL). Postoperative management included initial observation (34%), ADT (22.7%) and adjuvant RT+/-ADT (42.8%). Median follow-up was 42 months. Patients with cN+ on PSMA PET/CT had an increased risk of systemic progression (52.9% vs. 13.6% cN0 PSMA PET/CT vs. 21.5% cN0 at conventional imaging; P < .01). This held true at multivariable analysis: (HR 6.184, 95% CI: 3.386-11-295; P < .001) whilst no significant results were highlighted for Choline PET/CT. No significant associations for both PET types were found for local progression, BCR, and overall mortality (all P > .05). Observation as an initial management strategy instead of adjuvant treatments was related with an increased risk of metastases (HR 1.808; 95% CI: 1.069-3.058; P < .05). CONCLUSIONS: PSMA PET/CT cN+ patients with negative conventional imaging have an increased risk of systemic progression after RP compared to their counterparts with cN0M0 disease both at conventional and/or molecular imaging.

A Systematic Review of the Efficacy and Toxicity of Brachytherapy Boost Combined with External Beam Radiotherapy for Nonmetastatic Prostate Cancer.

CONTEXT: The optimum use of brachytherapy (BT) combined with external beam radiotherapy (EBRT) for localised/locally advanced prostate cancer (PCa) remains uncertain. OBJECTIVE: To perform a systematic review to determine the benefits and harms of EBRT-BT. EVIDENCE ACQUISITION: Ovid MEDLINE, Embase, and EBM Reviews-Cochrane Central Register of Controlled Trials databases were systematically searched for studies published between January 1, 2000 and June 7, 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Eligible studies compared low- or high-dose-rate EBRT-BT against EBRT ± androgen deprivation therapy (ADT) and/or radical prostatectomy (RP) ± postoperative radiotherapy (RP ± EBRT). The main outcomes were biochemical progression-free survival (bPFS), severe late genitourinary (GU)/gastrointestinal toxicity, metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS), at/beyond 5 yr. Risk of bias was assessed and confounding assessment was performed. A meta-analysis was performed for randomised controlled trials (RCTs). EVIDENCE SYNTHESIS: Seventy-three studies were included (two RCTs, seven prospective studies, and 64 retrospective studies). Most studies included participants with intermediate-or high-risk PCa. Most studies, including both RCTs, used ADT with EBRT-BT. Generally, EBRT-BT was associated with improved bPFS compared with EBRT, but similar MFS, CSS, and OS. A meta-analysis of the two RCTs showed superior bPFS with EBRT-BT (estimated fixed-effect hazard ratio [HR] 0.54 [95% confidence interval {CI} 0.40-0.72], p < 0.001), with absolute improvements in bPFS at 5-6 yr of 4.9-16%. However, no difference was seen for MFS (HR 0.84 [95% CI 0.53-1.28], p = 0.4) or OS (HR 0.87 [95% CI 0.63-1.19], p = 0.4). Fewer studies examined RP ± EBRT. There is an increased risk of severe late GU toxicity, especially with low-dose-rate EBRT-BT, with some evidence of increased prevalence of severe GU toxicity at 5-6 yr of 6.4-7% across the two RCTs. CONCLUSIONS: EBRT-BT can be considered for unfavourable intermediate/high-risk localised/locally advanced PCa in patients with good urinary function, although the strength of this recommendation based on the European Association of Urology guideline methodology is weak given that it is based on improvements in biochemical control. PATIENT SUMMARY: We found good evidence that radiotherapy combined with brachytherapy keeps prostate cancer controlled for longer, but it could lead to worse urinary side effects than radiotherapy without brachytherapy, and its impact on cancer spread and patient survival is less clear.

Potential Applications of New Headsets for Virtual and Augmented Reality in Urology.

Virtual and augmented reality (VR/AR) technologies hold great promise in various medical fields. The release of a new generation of headsets for medical enhanced VR/AR (MER) opens new possibilities for applications in medicine, particularly in urology, to improve accessibility to everyone. These innovative headsets offer deep immersion without requiring a controller, which represents a novel approach to VR/AR engagement. The potential of these headsets applies to all aspects of urology, including surgical training, virtual meetings, communication between health care providers, patient counseling, telemedicine, delivering patient advice, and pain control. MER has the potential to improve operative planning and enhance intraoperative navigation and spatial awareness. The surgeon's visualization and overall experience can be significantly enhanced via improved guidance and visualization, ultimately leading to greater precision and safety. This cutting-edge technology has the potential to reshape urology practice, communication methods, and medical procedures, and ultimately to improve patients' experience of their urological condition. PATIENT SUMMARY: This mini review explores how a new generation of headsets for medical enhanced virtual reality could revolutionize urology by improving surgical planning, assistance during procedures, and medical education. Patients can benefit from better pain management and a deeper understanding of their conditions. However, challenges such as costs, accuracy, and ethical concerns must be addressed. This technology holds promise for transforming urological practice and patient care.

Outcomes of Cytoreductive Radical Prostatectomy for Oligometastatic Prostate Cancer on Prostate-specific Membrane Antigen Positron Emission Tomography: Results of a Multicenter European Study.

BACKGROUND: De novo oligometastatic prostate cancer (omPCa) on prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is a new disease entity and its optimal management remains unknown. OBJECTIVE: To analyze the outcomes of patients treated with cytoreductive radical prostatectomy (cRP) for omPCa on PSMA-PET. DESIGN, SETTING, AND PARTICIPANTS: Overall, 116 patients treated with cRP at 13 European centers were identified. Oligometastatic PCa was defined as miM1a and/or miM1b with five or fewer osseous metastases and/or miM1c with three or fewer lung lesions on PSMA-PET. INTERVENTION: Cytoreductive radical prostatectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Thirty-day complications according to Clavien-Dindo, continence rates, time to castration-resistant PCa (CRPC), and overall survival (OS) were analyzed. RESULTS AND LIMITATIONS: Overall, 95 (82%) patients had miM1b, 18 (16%) miM1a, and three (2.6%) miM1c omPCa. The median prebiopsy prostate-specific antigen was 14 ng/ml, and 102 (88%) men had biopsy grade group ≥3 PCa. The median number of metastases on PSMA-PET was 2; 38 (33%), 29 (25%), and 49 (42%) patients had one, two, and three or more distant positive lesions. A total of 70 (60%) men received neoadjuvant systemic therapy, and 37 (32%) underwent metastasis-directed therapy. Any and Clavien-Dindo grade ≥3 complications occurred in 36 (31%) and six (5%) patients, respectively. At a median follow-up of 27 mo, 19 (16%) patients developed CRPC and eight (7%) patients died. The 1-yr urinary continence rate was 82%. The 2-yr CRPC-free survival and OS were 85.8% (95% confidence interval [CI] 78.5-93.7%) and 98.9% (95% CI 96.8-100%), respectively. The limitations include retrospective design and short-term follow-up. CONCLUSIONS: Cytoreductive radical prostatectomy is a safe and feasible treatment option in patients with de novo omPCa on PSMA-PET. Despite overall favorable oncologic outcomes, some of these patients have a non-negligible risk of early progression and thus should be considered for multimodal therapy. PATIENT SUMMARY: We found that patients treated at expert centers with surgery for prostate cancer, with a limited number of metastases detected using novel molecular imaging, have favorable short-term survival, functional results, and acceptable rates of complications.

Outcomes of a Diagnostic Pathway for Prostate Cancer Based on Biparametric MRI and MRI-Targeted Biopsy Only in a Large Teaching Hospital.

BACKGROUND: Diagnostic pathways for prostate cancer (PCa) balance detection rates and burden. MRI impacts biopsy indication and strategy. METHODS: A prospectively collected cohort database (N = 496) of men referred for elevated PSA and/or abnormal DRE was analyzed. All underwent biparametric MRI (3 Tesla scanner) and ERSPC prostate risk-calculator. Indication for biopsy was PIRADS ≥ 3 or risk-calculator ≥ 20%. Both targeted (cognitive-fusion) and systematic cores were combined. A hypothetical full-MRI-based pathway was retrospectively studied, omitting systematic biopsies in: (1) PIRADS 1-2 but risk-calculator ≥ 20%, (2) PIRADS ≥ 3, receiving targeted biopsy-cores only. RESULTS: Significant PCa (GG ≥ 2) was detected in 120 (24%) men. Omission of systematic cores in cases with PIRADS 1-2 but risk-calculator ≥ 20%, would result in 34% less biopsy indication, not-detecting 7% significant tumors. Omission of systematic cores in PIRADS ≥ 3, only performing targeted biopsies, would result in a decrease of 75% cores per procedure, not detecting 9% significant tumors. Diagnosis of insignificant PCa dropped by 52%. PCa undetected by targeted cores only, were ipsilateral to MRI-index lesions in 67%. CONCLUSIONS: A biparametric MRI-guided PCa diagnostic pathway would have missed one out of six cases with significant PCa, but would have considerably reduced the number of biopsy procedures, cores, and insignificant PCa. Further refinement or follow-up may identify initially undetected cases. Center-specific data on the performance of the diagnostic pathway is required.

The impact of a second MRI and re-biopsy in patients with initial negative mpMRI-targeted and systematic biopsy for PIRADS ≥ 3 lesions.

OBJECTIVE: To evaluate the proportions of detected prostate cancer (PCa) and clinically significant PCa (csPCa), as well as identify clinical predictors of PCa, in patients with PI-RADS > = 3 lesion at mpMRI and initial negative targeted and systematic biopsy (initial biopsy) who underwent a second MRI and a re-biopsy. METHODS: A total of 290 patients from 10 tertiary referral centers were included. The primary outcome measures were the presence of PCa and csPCa at re-biopsy. Logistic regression analyses were performed to evaluate predictors of PCa and csPCa, adjusting for relevant covariates. RESULTS: Forty-two percentage of patients exhibited the presence of a new lesion. Furthermore, at the second MRI, patients showed stable, upgrading, and downgrading PI-RADS lesions in 42%, 39%, and 19%, respectively. The interval from the initial to repeated mpMRI and from the initial to repeated biopsy was 16 mo (IQR 12-20) and 18 mo (IQR 12-21), respectively. One hundred and eight patients (37.2%) were diagnosed with PCa and 74 (25.5%) with csPCa at re-biopsy. The presence of ASAP on the initial biopsy strongly predicted the presence of PCa and csPCa at re-biopsy. Furthermore, PI-RADS scores at the first and second MRI and a higher number of systematic biopsy cores at first and second biopsy were independent predictors of the presence of PCa and csPCa. Selection bias cannot be ruled out. CONCLUSIONS: Persistent PI-RADS ≥ 3 at the second MRI is suggestive of the presence of a not negligible proportion of csPca. These findings contribute to the refinement of risk stratification for men with initial negative MRI-TBx.

Perioperative and Functional Results for Robot-assisted Radical Cystectomy with Totally Intracorporeal Neobladder in Male Patients via the Vesica Patavina (Ves.Pa.) Technique: IDEAL Stage 2a Report.

Background: Robot-assisted radical cystectomy (RARC) offers several advantages over open surgery, but intracorporeal neobladder construction (INC) is a challenging procedure. The vesica patavina (Ves.Pa.) refinement is a modification of the original technique that simplifies the neobladder configuration and reduces the risk of complications. Objective: To present a stage 2a IDEAL (Idea, Development, Exploration, Assessment and Long-term follow-up) report on RARC with INC using the Ves.Pa. technique. Design setting and participants: This was a prospective study of consecutive male patients undergoing RARC and Ves.Pa. INC performed by a single surgeon for muscle-invasive or non-muscle-invasive, bacillus Calmette-Guérin-refractory urothelial bladder cancer in a tertiary referral center. Surgical procedure: RARC with INC using the refined Ves.Pa. technique. Measurements: Complications were classified using the Clavien-Dindo scheme, and functional outcomes were assessed using validated questionnaires. Results and limitations: A total of 20 male patients were treated. The median operative time was 382 min, and the median estimated blood loss was 350 ml. The incidence of high-grade complications was extremely low, with only one patient experiencing a grade IIIa complication. All patients had clear surgical margins. At median follow-up of 12 mo, statistically significant differences in all the functional scores measured were observed. Specifically, 6-mo parameters were all significantly worse than at baseline (all p < 0.05). No patients required intermittent catheterization. Severe urinary incontinence was experienced by approximately 25% of the patients. The median number of pad used was 0 during the day and 1 at night. The study is limited by its small sample size, single-center design, and short follow-up. Conclusions: RARC with the refined Ves.Pa. technique for INC is safe, feasible, and replicable. The technique simplifies the procedure and reduces the risk of complications. The study results suggest acceptable oncological and functional outcomes over short-term follow-up. Patient summary: We report our initial experience with robot-assisted removal of the bladder and construction of a new bladder using our modified technique, called Ves.Pa., in patients with bladder cancer. The technique is simple to perform. We observed a low rate of high-grade complications, and patients had surgical margins negative for cancer in all cases and fair functional outcomes at 12-month follow-up.

Optimal combination therapy for metastatic hormone-sensitive prostate cancer: new evidence, challenges and unanswered questions.

PURPOSE OF REVIEW: To evaluate the evidence supporting treatment intensification in mHSPC, with a focus on possible indications for treatment in each clinical setting. RECENT FINDINGS: There is a growing armamentarium of treatment options for patients with metastatic hormone-sensitive prostate cancer (mHSPC). These include combinations of treatments such as androgen deprivation therapy (ADT), docetaxel, and new antiandrogenic therapies. Treatment intensification with chemotherapy or newer hormonal agents may improve patient's oncologic outcomes, but it can also come with additional toxicities and costs. Therefore, we need to take into account individual patient factors and preferences when deciding on the optimal combination therapy. Additionally, ongoing research is needed to identify biomarkers and new image techniques that can predict response to treatment and identify the best candidate for each treatment. SUMMARY: Challenges and unanswered questions regarding treatment intensification and de-intensification are still present. Further studies are still needed to identify which patients would benefit most from this approach to improve quality of life without compromising overall survival outcomes.

Real-world Outcomes and Predictive Biomarkers for 177Lutetium Prostate-specific Membrane Antigen Ligand Treatment in Metastatic Castration-resistant Prostate Cancer: A European Association of Urology Young Academic Urologists Prostate Cancer Working Group Multi-institutional Observational Study.

BACKGROUND: The European Association of Urology guidelines include the lutetium-177 (177Lu) PSMA-617 prostate-specific membrane antigen (PSMA) ligand as a therapy option for metastatic castration-resistant prostate cancer (mCRPC). A major challenge in clinical practice is to pursue a personalized treatment approach based on robust predictive biomarkers. OBJECTIVE: To assess the performance of 177Lu PSMA in real-world practice and to elaborate clinical biomarkers for evaluating treatment responses. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective observational study including 233 patients with mCRPC treated with 177Lu PSMA in eight high-volume European centers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Baseline characteristics and clinical parameters during and after 177Lu PSMA treatment were documented. Correlations to treatment response were analyzed using χ2 and log-rank tests, with differences between groups with and without disease progression calculated using a Mann-Whitney U test. Univariate and multivariate-adjusted hazard ratios (HRs) were measured using Cox proportional hazards models. RESULTS AND LIMITATIONS: A prostate-specific antigen (PSA) decrease of ≥30% was observed in 41.7%, 63.5%, and 77.8% of patients after the first, second, and third treatment cycle, respectively. Restaging performed via PSMA positron emission tomography-computed tomography revealed that 33.7% of patients had an imaging-based response, including two patients with a complete response, while 13.4% had stable disease. The median time to progression was 5 mo and the median time until the start of a consecutive antineoplastic therapy was 8.5 mo. Of importance, a PSA decrease ≥30% after the first two cycles of 177Lu PSMA (1 cycle: p = 0.0003; 2 cycles: p = 0.004), absolute PSA after the first three cycles (1 cycle: p = 0.011; 2 cycles: p = 0.0005; 3 cycles: p = 0.002), and a PSA doubling time >6 mo (p = 0.009) were significantly correlated to treatment response. Furthermore, gamma-glutamyl transferase ≤31 U/L at the start of 177Lu PSMA therapy was correlated with 1.5 times higher risk of progression for patients without but not with visceral metastases (p = 0.046). CONCLUSIONS: 177Lu PSMA is an effective treatment option in mCRPC in the real-world setting. A PSA decrease ≥30% after the first two cycles is an early marker of response that can be easily implemented in clinical practice. PATIENT SUMMARY: 177Lu PSMA is a radioactive agent approved for treatment of advanced prostate cancer. We reviewed its use outside of clinical trials for patients treated at eight European centers. We found that 177Lu PSMA is an effective treatment option in real-world practice. A PSA (prostate-specific antigen) decrease of ≥30% after the first two therapy cycles is an early indicator of response to treatment and can be used in personalizing treatments for patients.

Urology: a trip into metaverse.

PURPOSE: Metaverse is becoming an alternative world in which technology and virtual experiences are mixed with real life, and it holds the promise of changing our way of living. Healthcare is already changing thanks to Metaverse and its numerous applications. In particular, Urology and urologic patients can benefit in many ways from Metaverse. METHODS: A non-systematic literature review identified recently published studies dealing with Metaverse. The database used for this review was PubMed, and the identified studies served as the base for a narrative analysis of the literature that explored the use of Metaverse in Urology. RESULTS: Virtual consultations can enhance access to care and reduce distance and costs, and pain management and rehabilitation can find an incredible support in virtual reality, reducing anxiety and stress and improving adherence to therapy. Metaverse has the biggest potential in urologic surgery, where it can revolutionize both surgery planning, with 3D modeling and virtual surgeries, and intraoperatively, with augmented reality and artificial intelligence. Med Schools can implement Metaverse in anatomy and surgery lectures, providing an immersive environment for learning, and residents can use this platform for learning in a safe space at their own pace. However, there are also potential challenges and ethical concerns associated with the use of the metaverse in healthcare. CONCLUSIONS: This paper provides an overview of the concept of the metaverse, its potential applications, challenges, and opportunities, and discusses the implications of its development in Urology.

Neutrophil-to-lymphocyte ratio as a prognostic factor for patients with urothelial carcinoma of the bladder following radical cystectomy.

Introduction: The pre-treatment neutrophil-to-lymphocyte ratio (NLR) has been associated with adverse pathology or survival in a variety of malignancies, including urothelial carcinoma of the bladder (UCB) treated with radical cystectomy (RC). Whether the prognostic value of NLR is retained, or even increased, when measured postoperatively remains to be studied. In this study, we evaluated the association of preoperative and postoperative NLR with oncological outcomes following RC. Material and methods: The NLR was recorded in 132 consecutive patients with UCB treated with open RC: before surgery (NLR1), postoperatively within 2 days (NRL2), between 7 and 15 days after RC before discharge (NLR3), and a few days before recurrence or last available follow-up (NLR4). Results: When assessed by multivariate analysis NLR1 remained independently associated with a significantly increased risk of extravesical disease (pT 3-4) (OR = 1.4, p <0.01) and lymphovascular invasion (LVI) (OR = 1.40, 95% CI 1.09-1.83, p <0.01). NLR4 was independently associated with a significantly increased risk of cancer-specific mortality (CSM) (HR = 1.14, 95%CI 1.03-1.24, p = 0.013). In a postoperative model, NLR3 was found to be an independent predictor of all-cause mortality (ACM) [HR = 1.11, 95% CI 1.02-1.21, p = 0.01]. NLR1 was associated with a significantly increased risk of recurrence in the univariable preoperative model [HR = 1.9, 95%CI 1.00-3.65, p = 0.05], while in the postoperative model NLR4 remained independently associated with a significantly increased risk of recurrence (HR = 1.13, 95%CI 1.04-1.23, p = 0.03). Conclusions: In patients with UCB treated with RC, the NLR is associated with more advanced tumour stage, LVI, lymph node metastasis, and higher CSM. Furthermore, the variation of the NLR after surgery might play a role in predicting higher ACM and recurrence-free survival.

Identification of the Optimal Candidates for Nodal Staging with Extended Pelvic Lymph Node Dissection Among Prostate Cancer Patients Who Underwent Preoperative Prostate-specific Membrane Antigen Positron Emission Tomography. External Validation of the Memorial Sloan Kettering Cancer Center and Briganti Nomograms and Development of a Novel Tool.

BACKGROUND: Although the therapeutic role of extended pelvic lymph node dissection (ePLND) in patients with prostate cancer (PCa) is still under debate, this procedure is recommended for staging purposes in selected cases. Nomograms for predicting lymph node invasion (LNI) do not account for prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging, which is characterized by a high negative predictive value for nodal metastases. OBJECTIVE: To externally validate models predicting LNI in patients with miN0M0 PCa at PSMA PET and to develop a novel tool in this setting. DESIGN, SETTING, AND PARTICIPANTS: Overall, 458 patients with miN0M0 disease undergoing radical prostatectomy (RP) and ePLND at 12 centers between 2017 and 2022 were identified. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Available tools were externally validated using calibration plots, the area under the receiver operating characteristic curve (AUC), and decision curve analyses to assess calibration, discrimination, and the net benefit. A novel coefficient-based model was developed, internally validated, and compared with available tools. RESULTS AND LIMITATIONS: Overall, 53 patients (12%) had LNI. The AUC was 69% for the Briganti 2012, 64% for the Briganti 2017, 73% for the Briganti 2019, and 66% for the Memorial Sloan Kettering Cancer Center nomogram. Multiparametric magnetic resonance imaging stage, biopsy grade group 5, the diameter of the index lesion, and the percentage of positive cores at systematic biopsy were independent predictors of LNI (all p ≤ 0.04). Internal cross-validation confirmed a coefficient-based model with AUC of 78%, better calibration, and a higher net benefit in comparison to the other nomograms assessed. Use of a 5% cutoff would have spared 47% ePLND procedures (vs 13% for the Briganti 2019 nomogram) at the cost of missing only 2.1% LNI cases . The lack of central review of imaging and pathology represents the main limitation. CONCLUSIONS: Tools for predicting LNI are associated with suboptimal performance for men with miN0M0 PCa. We propose a novel model for predicting LNI that outperforms available tools in this population. PATIENT SUMMARY: Tools currently used to predict lymph node invasion (LNI) in prostate cancer are not optimal for men with negative node findings on PET (positron emission tomography) scans, leading to a high number of unnecessary extended pelvic lymph node dissection (ePLND) procedures. A novel tool should be used in clinical practice to identify candidates for ePLND to reduce the risk of unnecessary procedures without missing LNI cases.