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Table S1. Demographic and clinical characteristics of the analyzed patients; Table S2. Antibodies and conditions used for the IHC studies; Table S3. List of immune-related genes analyzed by Low Density Array; Figure S1. Gating and data analysis strategy; Figure S2. CD4+ and CD8+ T-cell differentiation in ccRCC TIL, and autologous PBL and RIL; Figure S3. Gap statistics according to the possible number of clusters of TIL phenotype. Optimal cut-off according to firstSEmax method (R package: cluster) is displayed (dotted line); Figure S4. PCA analysis including RIL and TIL phenotype. TIL clusters are displayed; Figure S5. Tumor size according to TIL clusters; Figure S6. Percentages of CD4+TIL expressing AM and InR according to tumor clusters. C1, Cluster1; C2, Cluster2; C3, Cluster3; Figure S7. Percentages of CD8+TIL expressing AM and InR according to tumor clusters. C1, Cluster1; C2, Cluster2; C3, Cluster3; Figure S8. Clonality Index and frequency of top 15 clonotypes in CD8+PD-1+ TIL according to tumor clusters. C1, Cluster1; C2, Cluster2; C3, Cluster3; Figure S9. Corrected P values for the differential gene expression between TIL clusters; Figure S10. Correlation matrix including TLS-related genes and immune cells densities in Immune-activated and Immune-regulated tumors; Figure S11. Percentages of CD4+PBL expressing differentiation markers, AM and InR in healthy controls (HC) and ccRCC-bearing patients; Figure S12. Percentages of CD8+PBL expressing differentiation markers, AM and InR in HC and ccRCC-bearing patients; Figure S13. Percentages of CD4+PBL expressing differentiation markers, AM and InR according to PBL Clusters; Figure S14. Percentages of CD8+PBL expressing differentiation markers, AM and InR according to PBL Clusters.

ImportanceFocal ablative irreversible electroporation (IRE) is a therapy that treats only the area of the tumor with the aim of achieving oncological control while reducing treatment-related functional detriment.ObjectiveTo evaluate the effect of focal vs extended IRE on early oncological control for patients with localized low- and intermediate-risk prostate cancer.Design, Setting, and ParticipantsIn this randomized clinical trial conducted at 5 centers in Europe, men with localized low- to intermediate-risk prostate cancer were randomized to receive either focal or extended IRE ablation. Data were collected at baseline and at regular intervals after the procedure from June 2015 to January 2020, and data were analyzed from September 2021 to July 2022.Main Outcomes and MeasuresOncological outcome as indicated by presence of clinically significant prostate cancer (International Society of Urological Pathology grade ≥2) on transperineal template-mapping prostate biopsy at 6 months after IRE. Descriptive measures of results from that biopsy included the number and location of positive cores.ResultsA total of 51 and 55 patients underwent focal and extended IRE, respectively. Median (IQR) age was 64 years (58-67) in the focal ablation group and 64 years (57-68) in the extended ablation group. Median (IQR) follow-up time was 30 months (24-48). Clinically significant prostate cancer was detected in 9 patients (18.8%) in the focal ablation group and 7 patients (13.2%) in the extended ablation group. There was no significant difference in presence of clinically significant prostate cancer between the 2 groups. In the focal ablation group, 17 patients (35.4%) had positive cores outside of the treated area, 3 patients (6.3%) had positive cores in the treated area, and 5 patients (10.4%) had positive cores both in and outside of the treated area. In the extended group, 10 patients (18.9%) had positive cores outside of the treated area, 9 patients (17.0%) had positive cores in the treated area, and 2 patients (3.8%) had positive cores both in and outside of the treated area. Clinically significant cancer was found in the treated area in 5 of 48 patients (10.4%) in the focal ablation group and 5 of 53 patients (9.4%) in the extended ablation group.Conclusions and RelevanceThis study found that focal and extended IRE ablation achieved similar oncological outcomes in men with localized low- or intermediate-risk prostate cancer. Because some patients with intermediate-risk prostate cancer are still candidates for active surveillance, focal therapy may be a promising option for those patients with a high risk of cancer progression.Trial RegistrationClinicalTrials.gov Identifier: NCT01835977

To the Editor:We read with great interest the recentmanuscript by Labbate et al reviewing the develop-ment of focal therapy in breast and prostate cancer(PCa).1Breast focal therapy (bFT) represents a suc-cessful model for organ-sparing cancer treatment, soas urologists sensible to prostate focal therapy (pFT)we can learn much about the complex process of bFTrecognition by the scientific community.

Multiparametric magnetic resonance imaging (mpMRI) is an invaluable diagnostic tool in the decision-making for prostate biopsies (PBx). However, a non-negligible proportion of patients with negative MRI (nMRI) may still harbour prostate cancer (PCa).To assess whether microultrasound (micro-US) can help in substratifying the presence of PCa and clinically significant PCa (csPCa; ie, any Gleason score ≥7 PCa) in patients with nMRI despite a persistently high clinical suspicion of PCa.A total of 125 biopsy-naïve patients who underwent micro-US-guided PBx with the ExactVu system for a persistently high suspicion of PCa despite nMRI were prospectively enrolled.The Prostate Risk Identification using micro-US (PRI-MUS) protocol was used to identify suspicious areas; PBx included targeted sampling of PRI-MUS ≥3 areas and systematic sampling.The primary endpoint was the assessment of micro-US diagnostic accuracy in detecting csPCa. Secondary endpoints included determining the proportion of patients with nMRI who may avoid PBx after micro-US or transrectal US, presence of cribriform and intraductal patterns on biopsy core examination, predictors of csPCa in patients presenting with nMRI, and comparing micro-US-targeted and systematic PBx in identifying csPCa.Considering csPCa detection rate, micro-US showed optimal sensitivity and negative predictive value (respectively, 97.1% and 96.4%), while specificity and positive predictive value were 29.7% and 34.0%, respectively. Twenty-eight (22.4%) patients with a negative micro-US examination could have avoided PBx with one (2.9%) missed csPCa. Cribriform and intraductal patterns were found in 14 (41.2%) and four (11.8%) of csPCa patients, respectively. In multivariable logistic regression models, positive micro-US, age, digital rectal examination, and prostate-specific antigen density ≥0.15 emerged as independent predictors of PCa. Targeted and systematic sampling identified 33 (97.1%) and 26 (76.5%) csPCa cases, respectively. The main limitation of the current study is represented by its retrospective single-centre nature on an operator-dependent technology.Micro-US represents a valuable tool to rule out the presence of csPCa among patients with a persistent clinical suspicion despite nMRI.According to our results, microultrasound (micro-US) may represent an effective tool for the diagnosis of clinically significant prostate cancer in patients with negative magnetic resonance imaging (nMRI), providing high sensitivity and negative predictive value. Further randomised studies are needed to confirm the potential role of micro-US in the diagnostic pathway of patients with a persistent suspicion of prostate cancer despite nMRI.

Background Focal Therapy (FT) for Prostate Cancer (PCa) is promising. However, long-term oncological results are awaited and there is no consensus on follow-up strategies. Molecular biomarkers (MB) may be useful in selecting, treating and following up men undergoing FT, though there is limited evidence in this field to guide practice. We aimed to conduct a consensus meeting, endorsed by the Focal Therapy Society, amongst a large group of experts, to understand the potential utility of MB in FT for localised PCa. Materials and methods A 38-item questionnaire was built following a literature search. The authors then performed three rounds of a Delphi Consensus using DelphiManager, using the GRADE grid scoring system, followed by a face-to-face expert meeting. Three areas of interest were identified and covered concerning MB for FT, i) the current/present role; ii) the potential/future role; iii) the recommended features for future studies. Consensus was defined using a 70% agreement threshold. Results Of 95 invited experts, 42 (44.2%) completed the three Delphi rounds. Twenty-four items reached a consensus and they were then approved at the meeting involving (n=15) experts. Fourteen items reached a consensus on uncertainty, or they did not reach a consensus. They were re-discussed, resulting in a consensus (n=3), a consensus on a partial agreement (n=1), and a consensus on uncertainty (n=10). A final list of statements were derived from the approved and discussed items, with the addition of three generated statements, to provide guidance regarding MB in the context of FT for localised PCa. Research efforts in this field should be considered a priority. Conclusions The present study detailed an initial consensus on the use of MB in FT for PCa. This is until evidence becomes available on the subject.

Focal instead of whole gland ablation for prostate cancer has been proposed to decrease treatment morbidity. We sought to determine differences in erectile function and urinary continence after focal and whole gland ablation for prostate cancer.From 2009 to 2018, 346 patients underwent high intensity focused ultrasound or cryotherapy for prostate cancer. Urinary continence was defined as use of no pads and sexual potency as enough erection for sexual penetration. Logistic regressions to treatment groups and covariates age, prostate specific antigen, International Society of Urological Pathology grading, prostate volume and energy modality were performed to access the effect of focal therapy in sexual potency and urinary continence after 3 and 12 months. IIEF-5 (International Index of Erectile Function) and I-PSS (International Prostate Symptom Score) questionnaires were evaluated. Propensity score matching was performed to adjust for potential baseline differences between groups.After exclusion, 195 post-focal therapy and 105 post-whole gland therapy patients were included in analysis. No significant difference was seen in baseline I-PSS and IIEF-5 scores. In multivariate models focal therapy was the most important factor related to sexual potency at 3 (OR 7.7) and 12 months (OR 3.9). Median IIEF-5 score at 3 months was 12 and 5 (p0.001), and at 12 months was 13 and 9 (p=0.04) in focal therapy and whole gland therapy groups, respectively. Focal therapy was the only factor related to continence (OR 0.7, p0.001). Results remained significant after propensity score matching.Focal ablation instead of whole gland therapy is the most important factor related to better sexual and urinary continence recovery after high intensity focused ultrasound and cryotherapy for prostate cancer.

Background: Minimally invasive cystectomy is being increasingly performed, however, data comparing laparoscopic radical cystectomy (LRC) and robotic radical cystectomy (RRC) are scarce. We compared...

Objectives To compare the lymph node (LN) yield and adequacy of laparoscopic pelvic lymph node dissection (L-PLND) and robot-assisted PLND (R-PLND), as PLND is a fundamental component of radical cystectomy (RC) for bladder cancer (BCa), where a positive status is the most powerful predictor of disease recurrence and survival. Patents and methods We retrospectively reviewed patients undergoing RC with PLND for BCa from January 2007 to July 2019 and grouped them in to L- and R-PLND. Until 2011, patients underwent a standard PLND (S-PLND) with the cranial limit as bifurcation of common iliac artery. Since 2012, an extended PLND (E-PLND) up to aortic bifurcation has been performed. An adequate S- and E-PLND were defined as those that yielded at least 10 and 16 LNs, respectively. The groups were compared for LN yield and adequacy of PLND. Results During the study period, 305 patients underwent minimally invasive RC in our centre, of which 274 (89.8%) underwent a concomitant PLND (98 L-PLND, 176 R-PLND). R-PLND resulted in a significantly greater median LN yield compared to L-PLND, both in the S-PLND (16 vs 11, P

A trend towards greater benefit from adjuvant chemotherapy (ACT) in pN+ bladder cancer (BCa) has been observed in multiple randomized controlled trials. However, it is still unclear which patients might benefit the most from this approach. We retrospectively analyzed a multicenter cohort of 1381 patients with pTany pN1-3 cM0 R0 urothelial BCa treated with radical cystectomy (RC) with or without cisplatin-based ACT. The main endpoint was overall survival (OS) after RC. We performed 1:1 propensity score matching to adjust for baseline characteristics and conducted a classification and regression tree (CART) analysis to assess postoperative risk groups and Cox regression analyses to predict OS. Overall, 391 patients (28%) received cisplatin-based ACT. After matching, two cohorts of 281 patients with pN+ BCa were obtained. CART analysis stratified patients into three risk groups: favorable prognosis (≤pT2 and positive lymph node [PLN] count ≤2; odds ratio [OR] 0.43), intermediate prognosis (≥pT3 and PLN count ≤2; OR 0.92), and poor prognosis (pTany and PLN count ≥3; OR 1.36). Only patients with poor prognosis benefitted from ACT in terms of OS (HR 0.51; p 0.001). We created the first algorithm that stratifies patients with pN+ BCa into prognostic classes and identified patients with pTany BCa with PLN ≥3 as the most suitable candidates for cisplatin-based ACT. PATIENT SUMMARY: We found that overall survival among patients with bladder cancer and evidence of lymph node involvement depends on cancer stage and the number of positive lymph nodes. Patients with more than three nodes affected by metastases seem to experience the greatest overall survival benefit from cisplatin-based chemotherapy after bladder removal. Our study suggests that patients with the highest risk should be prioritized for cisplatin-based chemotherapy after bladder removal.

Only 1 randomized controlled trial has compared focal therapy and active surveillance (AS) for the low-risk prostate cancer (PCa). We investigated whether focal HIFU (fHIFU) yields oncologic advantages over AS for low-risk PCa.We included 2 non-randomized prospective series of 132 (fHIFU) and 421 (AS) consecutive patients diagnosed with ISUP 1 PCa between 2008 and 2018. A matched pair analysis was performed to decrease potential bias. Study main outcomes were freedom from radical treatment (RT) or androgen-deprivation therapy (ADT), treatment-free survival (TFS), time to metastasis, and overall survival (OS).Median fHIFU follow-up was 50 months (interquartile range, 29-84 months). Among matched variables, no major differences were recorded except for AS having more suspicious digital rectal examination findings (P = .0074) and recent enrollment year (P = .0005). Five-year intervention-free survival from RT or ADT was higher for the fHIFU cohort (67.4% vs. 53.8%; P = .0158). Time to treatment was approximately 10 months shorter for AS than for fHIFU (time to RT, P = .0363; time to RT or ADT, P = .0156; time to any treatment, P = .0319). No differences were found in any-TFS (fHIFU, 61.4% vs. AS, 53.8%; P = .2635), OS (fHIFU, 97% vs. AS, 97%; P = .9237), or metastasis (n = 0 in fHIFU and n = 2 in AS; P = .4981). Major complications (≥ Clavien 3) were rare (n = 4), although 36.4% of men experienced complications. No relevant changes were noted in continence (P = .3949).At a 4-year median follow-up, fHIFU for mainly low-risk PCa (ISUP grade 1) is safe, may decrease the need for radical treatment or ADT and may allow longer time to treatment compared to AS. Nonetheless, no advantages are seen in PCa progression and/or death (OS).

Background: Robotic-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) is surging worldwide. Aim of the study was to perform a multicentric cost-analysis of RARC by comparing the gross cost of the intervention across hospitals in four different European countries. Methods: Patients who underwent RARC + ICUD were recruited from eleven European centers in four European countries (Belgium, France, Netherlands, and UK) between 2015 and 2020. Costs were divided into six parts: cost for hospital stay, cost for ICU stay, cost for surgical theater occupation, cost for transfusion, cost for robotic instruments, and cost for stapling instruments. These costs were individually assessed for each patient. Results: A total of 490 patients were included. Median operative time was 300(270–360) minutes and median hospital length-of-stay was 11(8–15) days. The average total cost of RARC was 14.794€ (95%CI 14.300–15.200€). A significant difference was found for the total cost, as well as the various subcosts abovementioned, between the four included countries. Different sets and types of robotic instruments were used by each center, leading to a difference in cost of robotic instrumentation. Nearly 84% of costs of RARC were due to hospital stay (42%), ICU stay (3%) and operative time (39%), while 16% of costs were due to robotic (8%) and stapling (8%) instruments. Conclusion: Costs and subcosts of RARC + ICUD vary significantly across European countries and are mainly dependent of hospital length-of-stay and operative time rather than robotic instrumentation. Decreasing length-of-stay and reducing operative time could help to decrease the cost of RARC and make it more widely accessible.

Background The occurrence of postoperative urinary incontinence (UI) remains a problem for patients undergoing robot-assisted radical prostatectomy (RARP). Non-surgical interventions (NSI) in addition to intraoperative techniques and patient behavioral changes have been proposed to improve urinary continence (UC) recovery after RARP. However, to date, the real clinical impact of postoperative NSI remains not well characterized. Materials and Methods We performed a Systematic Review in April 2021, using Allied and Complementary Medicine (AMED), Embase, and MEDLINE according to the PRISMA recommendations and using the Population, Intervention, Comparator and Outcome (PICO) criteria. Primary outcome of interest was the impact of NSI on UC recovery rate and time to achieve UC after RARP. Secondary outcomes of interest were the assessment of patient adherence to NSI, risk factors associated with UI, and correlation between postoperative NSI and sexual activity recovery. Results A total of 2758 articles were screened, and 8 full texts including 1146 patients were identified (3 randomized controlled trials, 3 prospective single-arm trials, and 2 retrospective series). Postoperative NSI of interest included pelvic floor muscle training (PFMT) (n = 6 studies) and administration of oral medications (solifenacin) (n = 2 studies). PFMT appeared to increase UC rates and to accelerate time to achieve UC in the early postoperative period. Similarly, solifenacin provided higher rates of UC recovery and contributed to a certain degree of symptomatic relief. There was a great variability regarding NSI features and data reporting among studies. Major limitations were the small sample sizes and the short follow-up. Conclusion Postoperative NSI to manage UI after RARP include PFMT and solifenacin administration. Both seem to modestly improve early UC recovery. Nonetheless, evidence supporting their routinely use is still weak and lacks appropriate follow-up to evaluate possible benefits on long-term UC recovery.

Focal therapy (FT) for prostate cancer (PCa) is emerging as a novel therapeutic approach for patients with low- to intermediate-risk disease, in order to provide acceptable oncological control, whilst avoiding the side effects of radical treatment. Evidence regarding the ideal follow-up strategy and the significance of prostate-specific antigen (PSA) kinetics after treatment is needed. In this study, we aimed to assess the value of the percentage of PSA reduction (%PSA reduction) after FT in predicting the likelihood of any additional treatment or any radical treatment. We retrospectively analysed a multicentre cohort of 703 men receiving FT for low- and intermediate-risk PCa. Overall, the rates of any additional treatment and any radical treatment were 30% and 13%, respectively. The median follow-up period was 41 mo. The median %PSA reduction after FT was 73%. At Cox multivariable analysis, %PSA reduction was an independent predictor of any additional treatment (hazard ratio [HR]: 0.96; p 90%, the probability of any additional treatment within 5 yr was 20%. Conversely, for %PSA reduction of

Purpose: Propose an approach of prostate cancer (PCa) patients during COVID-19 pandemic. Material and Methods: We conducted a review of current literature related to surgical and clinical management of patients during COVID-19 crisis paying special attention to oncological ones and especially those suffering from PCa. Based on these publications and current urological guidelines, a manual to manage PCa patients is suggested. Results: Patients suffering from cancer are likely to develop serious complications from COVID-19 disease together with an increased risk of postoperative morbidity and mortality. Therefore, the management of oncological patients should be taken into special consideration and most of the treatments postponed. In case the procedure is not deferrable, it should be adapted to the current situation. While the shortest radiotherapy (RT) regimens should be applied, surgical procedures must undergo the following recommendations proposed by main surgical associations. PCa prognosis is generally favourable and therefore one can safely delay most of the biopsies up to 6 months without interfering with survival outcomes in the vast majority of cases. In the same way, most of the localised PCa patients are suitable for active surveillance (AS) or hormonal therapy until local definitive treatment could be reconsidered. In metastatic as well as castration resistant PCa stages, adding androgen receptor targeted agents (abiraterone, apalutamide, darolutamide or enzalutamide) to androgen-deprivation therapy (ADT) could be considered in high risk patients. On the contrary, chemotherapy, immunotherapy and Radium-223 must be avoided with regard to the consequence of hematologic toxicity and risk of COVID-19 infection because of immunodepression. Conclusions: Most of the biopsies should be delayed while AS is advised in those patients with low risk PCa. ADT allows us to defer definitive local treatment in many cases of intermediate and high risk PCa. In regard to metastatic and castration resistant PCa, combination therapies with abiraterone, apalutamide, darolutamide or enzalutamide could be considered. Chemotherapy, Radium-223 and immunotherapy are discouraged.

Purpose:We compared cancer detection rates in patients who underwent magnetic resonance imaging cognitive guided micro-ultrasound biopsy vs robotic ultrasound magnetic resonance imaging fusion biop...

Objective To evaluate the role of the Vesical Imaging-Reporting and Data System (VI-RADS) score in the diagnostic pathway of bladder cancer. Methods A systemic search of the contemporary literature was performed in December 2019 using the Medical Literature Analysis and Retrieval System Online (MEDLINE), the Excerpta Medica dataBASE (EMBASE), and Web of Science databases focussing on all available articles on VI-RADS. Results Overall, six of 15 articles were included. All the available articles evaluated the ability of radiologists to use the VI-RADS score for discriminating non-muscle-invasive bladder cancer (NMIBC) from muscle-invasive bladder cancer (MIBC). Considering a cut-off VI-RADS score of >2, the sensitivity, specificity, positive (PPV) and negative predictive value (NPV) were 78–91.9%, 85–91%.1, 69–78%, and 88–97.1%, respectively. Considering a VI-RADS score cut-off of >3, the sensitivity, specificity, PPV and NPV were 77–94.6%, 43.9–96.5%, 51.6–86%, and 63.7–93%, respectively. Good interobserver agreement was demonstrated in the evaluated studies with a κ score of 0.73–0.89. Only one study evaluated the utility of VI-RADS in determining the presence of MIBC in patients treated with transurethral resection of the bladder diagnosed with high-grade T1 before the second transurethral resection using a VI-RADS score cut-off of >2; the sensitivity, specificity, PPV and NPV were 85%, 93.6%, 74.5%, and 96.6%, respectively. Conclusion The VI-RADS score, using multiparametric magnetic resonance imaging, showed excellent results in discriminating MIBC from NMIBC. Preliminary results have been reported for its use in patients with high-grade T1 bladder cancer. These results need to be validated in high-quality real-world settings. Abbreviations DCE: dynamic contrast enhancement; DWI: diffusion-weighted imaging; (N)MIBC: (non-)muscle-invasive bladder cancer; mpMRI: multiparametric MRI; TURBT: transurethral resection of bladder tumour; (N)(P)PV: (negative) (positive) predictive value; SC: structural category; T2W: T2-weighted; VI-RADS: vesical imaging-reporting and data system

Background Prostate biopsy is a standard tool for diagnosing prostate cancer, with more than 4 million procedures performed worldwide each year. Infectious complications and economic burden are reportedly rising with continued use of trans-rectal ultrasound-guided biopsy, despite the transperineal approach being associated with less infectious complications. Objective and methods In this review, the contemporary literature on pathophysiology, epidemiology, risk factors, causative organisms and emerging approaches for prevention of infectious complications are outlined. Results Management of infectious complications after TRUSB has caused significant financial burden on health systems. The most frequent causative agents of infectious complications after prostate biopsy are Gram-negative bacilli are particularly concerning in the era of antibiotic resistance. Increasing resistance to fluoroquinolones and beta-lactam antibiotics has complicated traditional preventive measures. Patient- and procedure-related risk factors, reported by individual studies, can contribute to infectious complications after prostate biopsy. Conclusions Recent literature shows that the transrectal ultrasound-guided prostate biopsy results in higher infectious complication rate than the transperineal prostate biopsy. NAATs, recently introduced technique to detect FQr may detect all antibiotic-resistant rectal microbiota members-included MDRs-although the technique still has limitations and economical burdens. Transient solutions are escalating antibiotic prophylaxis and widening the indications for TPB.

We report oncologic outcomes in patients treated with focal therapy for prostate cancer.We retrospectively analyzed a single institution cohort of men with localized prostate cancer who received focal therapy using high intensity focused ultrasound or cryotherapy from 2009 to 2018. Focal therapy was offered for low or intermediate risk disease (prostate specific antigen less than 20 ng/ml, Gleason score 7 or less and clinical stage T2b or less). Patients with previous prostate cancer treatment or less than 6 months of followup were excluded from study. Failure was defined as local or systemic salvage treatment, a positive biopsy Gleason score of 7 or greater in-field or out-of-field in nontreated patients, prostate cancer metastasis or prostate cancer specific death. Cox regression analysis was done to identify independent predictors of failure after focal therapy.Of the 309 patients included in study 190 and 119 were treated with high intensity focused ultrasound and cryotherapy, respectively. Median followup was 45 months. At 1, 3 and 5 years the failure-free survival rate was 95%, 67% and 54%, and the radical treatment-free survival rate was 99%, 79% and 67%, respectively. The 5-year metastasis-free survival rate was 98% and no prostate cancer specific death was registered in this cohort. Before focal therapy a biopsy Gleason score of 7 (3 + 4) or greater (HR 2.4, p0.001) and nadir prostate specific antigen (HR 2.2, p0.001) were independently associated with failed focal therapy. In the salvage focal therapy setting in-field recurrence after primary focal therapy was associated with poorer failure-free survival (p=0.02).Almost half of the men were free of focal therapy failure 5 years after treatment. Still, a significant proportion experienced recurrence at the midterm followup. The preoperative biopsy Gleason score and nadir prostate specific antigen were significantly associated with treatment failure.

Introduction: The health-related QoL is a patient-centered evaluation covering several aspects. This evaluation seems to be particularly important in patients submitted to radical cystectomy (RC) and urinary diversion with ileal conduit (IC) or a neobladder (NB). Objective: Review all recent data comparing QoL outcomes after radical cystectomy with NB and IC diversions. Evidence Acquisition: A systematic search in PubMed/Medline, Embase, and Cochrane databases was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement in December 2018. All articles published from January 01, 2012 to December 31, 2018, were included. A study was considered relevant if it compared QoL outcomes using validated questionnaires (EORTC QLQ C30, FACT-G, FACT-BL, FACT-VCI, and BCI). Evidence Synthesis: In 11 included studies, a total of 1389 participants were accounted (730 NB and 659 IC cases). The studies were conducted in 8 different countries, two were prospective, and none was randomized. There were two studies favoring results with a neobladder, 3 with incontinent diversion and 6 with no differences. The EORTC-QLQ-C30 was the most used instrument (5 studies) followed by FACT VCI and BCI (3 studies each). Given the heterogeneity of data and lack of prospective studies, a meta-analysis was not performed. Conclusion: No superiority of one urinary diversion was characterized. It seems that the choice must be individualized with an extensive preoperative orientation of the patient and their relatives. That will probably influence how the patient accepts the new condition.

To compare the accuracy in detecting variant histologies (VH) at transurethral resection of bladder (TURB) and radical cystectomy (RC) specimen among tertiary referral centres, in order to investigate potential reasons of discrepancies from the pathological point of view.Clinical and histopathological data of TURB specimen and subsequent cystectomy specimen of 3,445 RC candidate patients have been retrospectively collected from 24 tertiary referral centres between 1980 and 2021. VH considered in the analysis were pure squamous cell carcinoma, urothelial carcinoma with squamous differentiation, pure adenocarcinoma, urothelial carcinoma with glandular differentiation, micropapillary bladder cancer (BCa), neuroendocrine BCa, and other variants. The degree of agreement between TURB and RC concerning the identification of VH was expressed as concordance, classified according to Cohen's kappa coefficient.A VH was reported in 17% of TURB specimens, 45% of which were not confirmed in RC. The lowest concordance rate was reported for micropapillary BCa with 11 out of 18 (61%) centres reporting no agreement, whereas neuroendocrine BCa achieved the highest concordance rate with only 3 centres (17%) reporting no agreement. Our results shows that even among centres with the advantage of a referent uropathologist the micropapillary variant is characterized by scarce accuracy between TURB and RC. Differences in TURB specimen acquisition by the urologist and in sampling methods among different centres are the main limitations of the study.Accuracy of TURB in detecting VH is poor for certain VH, in particular for micropapillary BCa, with evident variation among centres. Novel diagnostic tools are required to better identify these VH and drive patients toward a personalized treatment.

To summarize current options available for robot-assisted partial nephrectomy RECENT FINDINGS: Partial nephrectomy (PN) is a standard treatment option for management of cT1 renal masses. It may be carried out by multiple approaches. Robot-assisted (RA) PN is one such option. The goal of treatment is both correct oncological (negative surgical margins) and functional (preservation of sufficient amount of renal parenchyma of the operated kidney) outcome. Appropriate outcomes depend on multiple factors. There are many, but among others tumor characteristics (size, location, i.e., tumor complexity), patient baseline renal function, patient comorbidities, and performance status etc. Based on all these, the surgeon adapts the intervention for each mass/patient by preoperative planning, absence/use/duration of warm or cold ischemia, perioperative imaging, resection technique adapted to tumor location and depth of invasion, use of hemostatics, type and degree of renal parenchymal closure and others details. Nephroprotective agents have not shown efficacy so far. It should not be forgotten that surgeon's experience plays a key role in the achievement of good results. Although multiple factors have a role in the RA partial nephrectomy, surgeon experience and adaptation of technique of intervention have the crucial role in the achievement of both functional and oncological results.

INTRODUCTION AND OBJECTIVE:To validate a prognostic nomogram (Necchi et al, nomogram-doi:10.1016/j.clgc.2018.09.008) for exclusive locoregional recurrence after radical cystectomy and bilateral pel...

INTRODUCTION AND OBJECTIVE:Prostate cancer (PCa) incidence in Asia is among the lowest in the world, although it has grown rapidly in recent years. We investigated the impact of race [Asian (ASI) o...

INTRODUCTION AND OBJECTIVE:Urinary incontinence(UI) and erectile dysfunction (ED) are common complications of radical prostatectomy(RP) with devastating impact on quality of life(QoL). Baseline cha...

INTRODUCTION AND OBJECTIVE:To externally validate the COBRA score (tool predicting cancer-specific survival after radical cystectomy for urothelial carcinoma; Welty et al Cancer 2017, DOI: 10.1002/...

INTRODUCTION AND OBJECTIVE:Our aim was to evaluate the expression of CD34 and FSHR in different renal cancers (RCa) and their ability in differentiating benign from malignant diseases.METHODS:A 10x...

Simple Summary This study tested the feasibility and reliability of a novel digital microscopy technique in assessing ablation margins during partial prostate gland cryoablation. Though preliminary, findings suggest that this novel technique may increase the efficacy of focal treatments, by reducing the risk of untreated prostate cancer areas not visible to an MRI, as well as safety, by more precisely sparing uninvolved areas and surrounding structures. Abstract Partial gland cryoablation (PGC) aims at destroying prostate cancer (PCa) foci while sparing the unaffected prostate tissue and the functionally relevant structures around the prostate. Magnetic Resonance Imaging (MRI) has boosted PGC, but available evidence suggests that ablation margins may be positive due to MRI-invisible lesions. This study aimed at determining the potential role of intraoperative digital analysis of ablation margins (DAAM) by fluoresce confocal microscopy (FCM) of biopsy cores taken during prostate PGC. Ten patients with low to intermediate risk PCa scheduled for PGC were enrolled. After cryo-needles placement, 76 biopsy cores were taken from the ablation margins and stained by the urologist for FCM analysis. Digital images were sent for “real-time” pathology review. DAAM, always completed within the frame of PGC treatment (median time 25 min), pointed out PCa in 1/10 cores taken from 1 patient, thus prompting placement of another cryo-needle to treat this area. Standard HE evaluation confirmed 75 cores to be cancer-free while displayed a GG 4 PCa in 7% of the core positive at FCM. Our data point out that IDAAM is feasible and reliable, thus representing a potentially useful tool to reduce the risk of missing areas of PCa during PGC.

Objectives To evaluate whether continuing the antiplatelet drug acetylsalicylic acid≤100mg (ASA) during Robotic-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) increases the risk of peri-and postoperative hemorrhagic complications and overall morbidity. Indeed, guidelines recommend interrupting antiplatelet therapy before radical cystectomy; however, RARC with ICUD is associated to reduced estimated blood loss and blood transfusions compared to its open counterpart. Methods Data from a multicentric European database were analyzed. All participating centers maintained a prospective database of patients undergoing RARC with ICUD. We identified patients receiving antiplatelet therapy by acetylsalicylic acid ≤100mg. Patients were divided into three groups: those not taking acetylsalicylic acid (no-ASA), those where ASA was continued perioperatively (c-ASA) and those where ASA was interrupted perioperatively (i-ASA). Estimated blood loss and peri-and post-operative transfusions were recorded. Hemorrhagic complications, ischemic, thrombotic and cardiac morbidity was recorded and classified using the Clavien-Dindo score by a senior urologist. Results 640 patients were analyzed. Patients on acetylsalicylic acid were significantly older and had more comorbidities. No significant difference was found for estimated blood loss between no-ASA, c-ASA and i-ASA (280 vs. 300 vs. 200ml respectively; P = 0.09). Similarly, no significant difference was found for intraoperative (5% vs. 9% vs. 11%; P = 0.07) and postoperative transfusion rate (11% vs. 13% vs. 18%; P = 0.17). Higher ischemic complications were noted in the i-ASA group compared to no-ASA and c-ASA (4% vs. 0.6% vs. 1.4%; P = 0.03). On uni and multivariate logistic regression, continuing acetylsalicylic acid was not significantly associated to either major complications or post-operative transfusions. Conclusions Peri-operative acetylsalicylic acid continuation in RARC with ICUD does not increase hemorrhagic complications. Interrupting acetylsalicylic acid peri-operatively may expose patients to a higher risk of ischemic events.

The complement system plays a complex role in cancer. In clear cell renal cell carcinoma (ccRCC), local production of complement proteins drives tumor progression, but the mechanisms by which they do this are poorly understood. We found that complement activation, as reflected by high plasma C4d or as C4d deposits at the tumor site, was associated with poor prognosis in two cohorts of patients with ccRCC. High expression of the C4-activating enzyme C1s by tumor cells was associated with poor prognosis in three cohorts. Multivariate Cox analysis revealed that the prognostic value of C1s was independent from complement deposits, suggesting the possibility of complement cascade–unrelated, protumoral functions for C1s. Silencing of C1s in cancer cell lines resulted in decreased proliferation and viability of the cells and in increased activation of T cells in in vitro cocultures. Tumors expressing high levels of C1s showed high infiltration of macrophages and T cells. Modification of the tumor cell phenotype and T-cell activation were independent of extracellular C1s levels, suggesting that C1s was acting in an intracellular, noncanonical manner. In conclusion, our data point to C1s playing a dual role in promoting ccRCC progression by triggering complement activation and by modulating the tumor cell phenotype and tumor microenvironment in a complement cascade–independent, noncanonical manner. Overexpression of C1s by tumor cells could be a new escape mechanism to promote tumor progression. See related Spotlight by Magrini and Garlanda, p. 855. See article by Daugan et al., p. 909 (40).

To compare laparoscopic partial nephrectomy (LPN) and robot-assisted partial nephrectomy (RAPN) performed in two European tertiary centers using the classic optimal surgical definition — “MIC” — and a new optimal surgical definition: the “Novel TRIFECTA” (NT) concept. We sought to strengthen the PN evidence and to test the NT’s performance. The study population comprehended 505 cases of localized kidney cancer from two tertiary centers between 2012 and 2019. The NT achievement was higher in the RAPN group when compared to LPN (70.5 vs. 87.4%; p = 0.004), while no differences were found when considering the MIC criteria. Also, a similar high-grade complications rate (Clavien-Dindo > III) and operative time (105 min vs. 100 min; p = NS) were found. In the multivariable regression, the RAPN approach was a predictor of NT achievement (OR 2.45; p = 0.008). NT achievement was higher in the RAPN group, while similar results were found when evaluating the MIC criteria. The NT definition could be more sensitive to the individual-specific responses related to the PN.

The use of renal tumor biopsy (RTB) for small renal masses (SRMs) in daily practice, although safe and accurate, is unusual. Considering the large number of benign tumors in patients with renal masses 4 cm, some patients with benign tumors are directly referred for surgery instead. This study aimed to report the diagnostic rates of RTB, determine the concordance with surgical pathology, and assess the number of procedures that could have been avoided. We retrospectively studied 255 patients who underwent RTB at our institution in 2010-2019. Of them, 73 were excluded from the analysis (exclusion criteria: 4 cm, cystic lesion, missing data). The remaining 182 with undetermined SRMs ≤ 4 cm underwent RTB under computed tomography guidance.Biopsies were diagnostic in 154/182 (84.6%) cases. Of the non-diagnostic biopsies, 11 were diagnostic when repeated. When RTB was performed of all undetermined SRMs, active treatment (surgery or cryotherapy) was avoided in 50/182 patients (27.5%) because of a benign diagnosis, while 9/182 patients (4.9%) underwent surveillance after a shared multidisciplinary decision. The overall diagnostic rate was 90.6%. All adverse events (approximately 4%) were Clavien-Dindo grade I and did not require active treatment. RTB histology results and nuclear grade were highly concordant with the final pathology (96% and 86.6%, respectively). On univariate logistic regression analysis, male sex was the only contributing factor of diagnostic biopsy. RTB of SRMs should be performed more frequently as part of a multidisciplinary decision-making process since it avoided unnecessary surgical treatment in 1 of 3 patients in our institution.

We assessed whether prostate cancer (PCa) location might affect oncologic outcomes after focal therapy (FT) for PCa.We identified 274 men receiving FT for PCa using either high intensity focused ultrasound (HIFU) or cryotherapy at a high volume center between 2009 and 2018. Survival analyses using Kaplan-Meier method were used to assess any additional treatment and radical treatment rates according to PCa location. Propensity-score match analysis was used to compare oncologic outcomes of HIFU vs cryotherapy according to PCa location. Covariates were prostate specific antigen, clinical stage, prostate volume, Gleason score, maximum cancer core length, percentage of positive cores and treatment modality.A total of 166 and 108 men received FT with HIFU and cryotherapy, respectively. Overall, 39% (106) and 31% (85) received at least an additional treatment and a radical treatment after FT, respectively, with a median followup of 51 months. At 36 months' followup, the rates of any additional treatment-free survival were 71%, 75%, and 69% for patients with basal, mid-prostate and apical disease, respectively (p=0.7). At multivariable logistic regression analysis, PCa location was not significantly associated with higher risk of either any additional treatment or radical treatment (all p0.4). After matching, there was no difference between HIFU vs cryotherapy in terms of any additional treatment rates according to PCa location.The PCa location does not significantly affect the rate of failure after FT. The presence of an apical lesion should not be considered an exclusion criteria for FT. Both HIFU and cryotherapy likely achieve similar medium-term oncologic results regardless of PCa location.

OBJECTIVES To evaluate the technical feasibility, oncological and functional outcomes of nerve sparing cystoprostatectomy (NSCP) and prostate capsule-sparing cystectomy (PCSC) for the treatment of organ-confined bladder cancer at a single referral centre. PATIENTS AND METHODS From April 2001 to June 2012, 60 patients underwent PCSC and 47 were treated with NSCP. Inclusion criteria for PCSC were: fully informed consent for the well-motivated patient; negative transurethral resection of the bladder neck; normal prostatic specific antigen (PSA) level (defined as

There are few data on the outcomes and toxicity of radical prostatectomy (RP) among men experiencing local recurrence of prostate cancer (PC) following focal therapy (FT). To characterise perioperative, oncological, and functional outcomes after salvage robot-assisted RP (S-RALP) and determine the risk factors for S-RALP failure, we conducted a multicentre cohort study of 82 patients undergoing S-RALP after FT. All had histological confirmation of PC recurrence, with metastatic disease excluded using pelvic magnetic resonance imaging, a bone scan, and/or positron emission tomography/computed tomography. Progression-free survival was 74%, 48%, and 36% at 12, 24, and 36mo after surgery, respectively. The 12-mo continence rate was 83%. There were no intraoperative complications and no major postoperative complications. On multivariable analysis, only infield recurrence (hazard ratio [HR] 3.77, 95% confidence interval [CI] 1.11-12.85; p=0.03) and pT3b stage (HR 5.0, 95% CI 1.53-16.39; p=0.008) were independent predictors of recurrence. This study represents the largest series of salvage surgery after FT and shows that this approach is safe with no increase in toxicity when compared to primary RALP. Men identified as having infield recurrence after FT appear to have phenotypically aggressive disease and should be counselled regarding the potential need for a multimodal therapeutic approach. PATIENT SUMMARY: Robotic surgery after focal therapy for prostate cancer is safe and achieves postoperative continence results similar to those for robotic radical prostatectomy in treatment-naïve patients. However, if the cancer recurrence is within the previously treated field, the oncological prognosis seems to be worse.

Purpose: Today, up to one-third of newly diagnosed prostate cancer (PCa) cases may be suitable for focal treatment. The lack of data about the toxicity profiles of lesion-targeting therapies, however, has made it difficult to compare treatment modalities. The aim of the present study was to evaluate comprehensively the incidence, severity, and timing of onset of complications for PCa patients undergoing focal high-intensity focused ultrasound (HIFU) and focal cryosurgical ablation of the prostate (CSAP). Materials and Methods: A total of 336 patients were included who underwent focal HIFU or focal CSAP as a primary treatment for PCa between January 2009 and December 2017. Mean follow-up was 11 months (standard deviation: 3.0). All complications were captured and graded according to severity, and classified by timing of onset. Univariate and multivariate analysis was performed to identify predictors of the most common side effects. Results: There were 98 complications in 79/210 patients (38%) undergoing focal HIFU and 34 complications in 27/126 patients (21%) undergoing focal CSAP. In terms of severity, 95% of the complications of focal HIFU and 91% of the complications of focal CSAP were minor. Most complications presented in the early postoperative period. On multivariate analysis, subtotal HIFU was associated with acute urinary retention (AUR), while a smaller prostate size and longer catheterization time with dysuria. In CSAP patients, longer catheterization time was associated with AUR and urethral sloughing. The main limitation is the nonrandomized and retrospective nature. Conclusions: Focal HIFU and focal CSAP provide a tolerable toxicity, with primarily minor complications presenting in the early postoperative period.

The significance of upstaging of cT1 renal tumors to pT3a is not clear. We evaluate the incidence of upstaging, identify predictors and analyze oncological outcomes of these patients versus those who did not upstage. We also compared the oncological outcomes of cT1 upstaging to pT3a with de novo pT3a renal tumors.From a database of 1021 renal tumors with complete available follow-up data, 517 patients had cT1. Patients upstaging to pT3a were compared to those who did not. Baseline clinical, perioperative, histopathologic features and oncological outcomes were analysed.Out of 517 cT1 patients, 105 (20.3%) upstaged to pT3a and 412 (79.7%) did not. Proportion of patients in each group undergoing partial and radical nephrectomy, postoperative tumor size, histology, margin status and lymph node involvement were similar. Among upstaged, 9 patients (8.6%) developed first recurrence as compared to only 3 (0.7%) in those not upstaging (P 0.001). The median time to recurrence (57 vs. 107 months; P 0.001) was lesser in de novo pT3a renal tumors.Pathological upstaging from cT1 to pT3a and necrosis on histopathology were associated with recurrence. Advanced age, smoking, necrosis on histopathology, clear cell histology and higher Fuhrman grades contributed to pathological upstaging of cT1 tumors. De novo pT3a RCC had worse survival when compared to cT1 patients upstaging to pT3a RCC.

Whether focal therapy (FT) jeopardizes subsequent prostate cancer (PCa) salvage treatments, when needed, remains a major concern and is largely unknown. To describe and report safety, oncological and functional outcomes of salvage treatments following PCa recurrence and/or persistence after FT. A systematic review on salvage treatments for PCa recurrence/persistence after FT was carried out according to the PRISMA guidelines using an ‘a priori protocol’. A comprehensive literature review was also performed to investigate options to treat FT PCa recurrence/persistence that have not yet been reported after FT. Four retrospective series were included (n = 67 men); overall quality of the studies was low. Salvage treatments yielded 32.8% (n = 22 of 67) biochemical recurrence rate (BCR) after a 7–62-months mean follow-up. No cancer-related deaths occurred. Patients experienced acceptable complications (n = 12 patients; n = 8 Clavien 3) and rare severe incontinence (4.5% using > 2 pads/day). Erectile function (EF) was rarely assessed (62.8% no information available), being overall poor. Other salvage options have been reported following whole-gland ablation and include: (1) re-do ablation yielding worst BCR and EF but similar complications and continence compared to first line ablation; (2) salvage radiotherapy yielding 16.6–38.8% BCR and acceptable toxicity profile with urinary and EF being poorly assessed. Current evidence is weak and limited to a few retrospective series. Oncological control is acceptable although it seems lower compared to a primary treatment setting. Functional outcomes are comparable to primary treatment with the exception of EF; overall, suggesting FT has little impact on subsequent salvage treatments. Future studies are needed to confirm the current findings.

To update current recommendations on prevention, screening, diagnosis, and evaluation of bladder cancer (BC) based on a thorough assessment of the most recent literature on these topics. A non-systematic review was performed, including articles until June 2017. A variety of original articles, reviews, and editorials were selected according to their epidemiologic, demographic, and clinical relevance. Assessment of the level of evidence and grade of recommendations was performed according to the International Consultation on Urological Diseases grading system. BC is the ninth most common cancer worldwide with 430,000 new cases in 2012. Currently, approximately 165,000 people die from the disease annually. Absolute incidence and prevalence of BC are expected to rise significantly during the next decades because of population ageing. Tobacco smoking is still the main risk factor, accounting for about 50% of cases. Smoking cessation is, therefore, the most relevant recommendation in terms of prevention, as the risk of developing BC drops almost 40% within 5 years of cessation. BC screening is not recommended for the general population. BC diagnosis remains mainly based on cystoscopy, but development of new endoscopic and imaging technologies may rapidly change the diagnosis algorithm. The same applies for local, regional, and distant staging modalities. A thorough understanding of epidemiology, risk factors, early detection strategies, diagnosis, and evaluation is essential for correct, evidence-based management of BC patients. Recent developments in endoscopic techniques and imaging raise the hope for providing better risk-adopted approaches and thereby improving clinical outcomes.