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Bladder outlet obstruction alters detrusor contractility, reducing the bladder's ability to respond to large filling with a risk of urinary retention. The objective was to assess the effect of bladder filling volume on detrusor contractility in men with bladder outlet obstruction.A prospective multicenter study in two pelviperineology departments. Male patients eligible for urodynamics (IPSS score 7) were included from January to July 2022. In case of absence of bladder outlet obstruction on pressure-flow studies, they were secondarily excluded. The primary endpoint was the maximum isometric detrusor pressure during a stop-test, corresponding to detrusor contractility, measured at 3 filling volumes (50%, 75%, and 100% of cystometric capacity).Fifty-two patients performed urodynamics, of whom 12 were excluded because of lack of obstruction or inability to perform the stop-test. Detrusor contractility was significantly higher for a 75% bladder filling than 50% and for a 75% filling than 100%, with a mean difference of 19.5; confidence interval (CI) 95% [14.3; 24.8] and 12.2; CI 95% [6.9; 17.5] cmHIn case of bladder outlet obstruction in men, detrusor contractility depends on bladder filling volume, with reduced contractility when the bladder was underfilled or overfilled. This phenomenon could help to explain the mechanisms of urinary retention in men with bladder outlet obstruction.

Supplementary Figure from Escherichia coli–Specific CXCL13-Producing TFH Are Associated with Clinical Efficacy of Neoadjuvant PD-1 Blockade against Muscle-Invasive Bladder Cancer

Biomarkers guiding the neoadjuvant use of immune-checkpoint blockers (ICB) are needed for patients with localized muscle-invasive bladder cancers (MIBC). Profiling tumor and blood samples, we found that follicular helper CD4+ T cells (TFH) are among the best therapeutic targets of pembrolizumab correlating with progression-free survival. TFH were associated with tumoral CD8 and PD-L1 expression at baseline and the induction of tertiary lymphoid structures after pembrolizumab. Blood central memory TFH accumulated in tumors where they produce CXCL13, a chemokine found in the plasma of responders only. IgG4+CD38+ TFH residing in bladder tissues correlated with clinical benefit. Finally, TFH and IgG directed against urothelium-invasive Escherichia coli dictated clinical responses to pembrolizumab in three independent cohorts. The links between tumor infection and success of ICB immunomodulation should be prospectively assessed at a larger scale.Significance:In patients with bladder cancer treated with neoadjuvant pembrolizumab, E. coli–specific CXCL13 producing TFH and IgG constitute biomarkers that predict clinical benefit. Beyond its role as a biomarker, such immune responses against E. coli might be harnessed for future therapeutic strategies.This article is highlighted in the In This Issue feature, p. 2221

International audience; CONTEXT: The advent of immune check inhibitors (ICIs) has tremendously changed the prognosis of metastatic renal cell carcinoma (mRCC), adding an unseen substantial overall survival benefit. These agents could be administered alone or in combination with anti-vascular endothelial growth factor (anti-VEGF) therapies. So far, treatment allocation is based only on clinical stratification risk models. OBJECTIVE: Herein, we aimed to report the different molecular classifications reported in the first-line treatment of mRCC and discuss the awaited clinical implications in terms of treatment selection. EVIDENCE ACQUISITION: Medline database as well as European Society for Medical Oncology (ESMO)/American Society of Clinical Oncology (ASCO) conference proceedings were searched to identify biomarker studies. Inclusion criteria comprised randomized and nonrandomized clinical trials that included patients treated in the first line of mRCC setting, patients treated with anti-VEGF therapies or ICIs, biological modeling, and available survival outcomes. EVIDENCE SYNTHESIS: Four classification models were identified with subsequent clinical implications: Beuselinck model (34 gene signatures), IMmotion150, Hakimi, and JAVELIN 101 model. Tumor profiling shows distinct outcomes when treated with one or other combination. Patients are clustered into two gene signatures: angiogenic and proinflammatory (as per JAVELIN). The first is more likely to respond to therapy that includes anti-VEGF agents, while the best outcomes are obtained with an ICI combination with the second. CONCLUSIONS: The findings presented here were mostly derived from ancillary registered studies of new drugs in the setting of mRCC. Further validation is needed, which sets new paradigms for investigation in clinical research based on tumor biology for treatment allocation and not only on clinical stratification tools. PATIENT SUMMARY: First-line treatment of metastatic kidney includes immunotherapy alone or in combination with antiangiogenic therapy. However, clinical practice demonstrated that the "one treatment fits all" strategy might not be the best approach. In fact, recent studies showed that the addition of immunotherapy agents will not benefit all patients equally, and some still respond either equally to or better than anti-vascular endothelial growth factor alone. This review revealed biomarker modeling that impacts treatment selection. Recent tumor profiling into "angiogenic signature" more sensitive to angiogenic agents versus "immune signature" more likely to achieve the best response with immunotherapy should be validated. Tumor biology features might be more powerful than clinical classification for a tailored treatment approach.

To assess the oncological outcomes of renal cell carcinoma (RCC) associated with tumor thrombus and identify predictive factors of recurrence.Multi-institutional study that included patients with cT3-4N0-1M0 RCC with tumoral thrombus identified in the prospective UroCCR database (CNIL DR 2013-206; NCT03293563). pT3a without involvement of the renal vein were excluded. All patients underwent radical nephrectomy and a thrombectomy of the renal vein ± inferior vena cava ± right atrium. The primary endpoint was recurrence-free survival (RFS). Thirty-two patients who had adjuvant therapies (tyrosine kinase inhibitors or mTOR inhibitor) were compared to control group (surveillance) in a propensity score-matched 1:1 sub-analysis RESULTS: A total of 432 patients were included: 70.4% pT3a, 20.1% pT3b, 4.2% pT3c and 5.3% pT4. Tumor characteristics were: 90.7% clear cell RCC, 13.9% pN1, and 87.1% high Fuhrman grade. 173 patients (40%) had disease recurrence, and median RFS was 37.3 months (95% CI, 26.4-46.7). In a multivariate analysis (Cox model), predictive factors of recurrence were: pT4 (HR 2.66; 95% CI, 1.42-4.99; p = 0.002), pN1 (HR 2.53; 95% CI, 1.46-4.39; p 0.001), tumor necrosis (HR 2.92; 95% CI, 1.85-4.62; p 0.001), tumor size 10 cm (HR 1.56; 95% CI, 1.08-2.24; p = 0.018). Adjuvant therapy was a protective factor of cancer recurrence (HR 0.33; 95% CI, 0.17-0.66; p = 0.002). Propensity score-matched sub-analysis of adjuvant vs control (surveillance) confirmed adjuvant treatment as a protective factor of cancer recurrence (Log rank p = 0.015).In this contemporary multi-institutional cohort of RCC + tumor thrombus, we reported higher recurrence rate shortly after surgical excision and demonstrated an oncological benefit of adjuvant treatment.

Resume Introduction La surveillance active (SA) des angiomyolipomes (AML) du rein est sous-utilisee a cause d’un dogme ancien faisant craindre un saignement menacant lorsque la taille tumorale depasse 4 cm. L’objectif de cette etude etait d’evaluer les resultats de la SA chez les patients pris en charge pour des AML sporadiques dont la taille etait superieure a 4 cm. Methodes Les resultats de la SA de 35 patients pris en charge pour des AML sporadiques du rein de plus de 4 cm etaient analyses retrospectivement. Durant la SA, la croissance tumorale, la survenue de nouveaux symptomes et/ou complications, l’arret du protocole de surveillance, le motif de sortie et le traitement offert a la sortie etaient recueillis. Resultats Avec un suivi moyen de 36 mois, 16 (46 %) patients etaient sortis de la SA (suivi moyen 55 ± 66, mediane : 36 mois). Les patients qui avaient arrete la SA etaient plus symptomatiques au diagnostic, mais avaient un âge, une taille tumorale moyenne et un sex-ratio similaire a ceux qui sont toujours pris en charge en SA. Le taux de survie sans traitement actif etait de 66 % a 5 ans. L’hemorragie retroperitoneale etait rapportee chez 3 (8,5 % de l’ensemble et 19 % des patients qui avaient arrete la SA) patients. Aucune de ces hemorragies n’avait necessite une transfusion ou une surveillance en unite de soins intensifs. Les autres motifs etaient la douleur (37 %), la preference patient (19 %), la modification de l’aspect radiologique de la tumeur (19 %) et l’hematurie (6 %). Conclusion Cette etude a montre que la SA des AML etait faisable meme chez les patients avec des tumeurs de plus de 4 cm. Plus de 50 % des patients etaient encore sous SA a 5 ans. L’arret de la SA n’etait pas lie a des complications hemorragiques dans la plupart des cas. Niveau de preuve 3.

Summary Objective. – To update the French guidelines on kidney cancer. Methods. – A systematic review of the literature between 2015 and 2020 was performed. The most relevant articles regarding the diagnosis, the classification, surgical treatment, medical treatment and follow-up of kidney cancer were retrieved and included in the new guidelines. The guidelines were updated with corresponding levels of evidence. Results. – Thoraco-abdominal CT scan with injection is the best radiological exam for the diagnosis of kidney cancer. MRI and contrast ultra-sound can be useful in some cases. Percutaneous biopsy is recommended when histological results will affect clinical decision. Renal tumours must be classified according to pTNM 2017 classification and ISUP grade. Metastatic kidney cancers must be classified according to IMDC criteria. Partial nephrectomy is the recommended treatment for T1a tumours and can be done through an open, laparoscopic or robotic access. T1b tumours can be treated by partial or total nephrectomy according to tumour complexity. Radical nephrectomy is the recommended treatment of advanced localized tumours. There is no recommended adjuvant treatment. In metastatic patients: cyto-reductive nephrectomy can be offered in case of good prognosis; medical treatment must be counseled first in case of intermediate or bad prognosis. Surgical or local treatment of metastases should be considered in case of solitary lesion or oligo-metastases. First line recommended drugs in metastatic patients include the associations axitinib/pembrolizumab and nivolumab/ipilimumab. Cystic tumours must be classified according to Bosniak Classification. Surgical excision should be offered to patients with Bosniak III and IV lesions. It is recommended to follow patients clinically and with imaging according to tumour aggressiveness. Conclusion. – These updated recommendations should assist French speaking urologists for their management of kidney cancers.

Objectives To evaluate the risk of contracting severe COVID‐19, defined as COVID‐19 specific intensive care unit (ICU) admission or death, for patients undergoing urological surgery during the epidemic. To define consequences of receiving surgery for COVID‐19 patients. Patients and Methods This is a multicenter observational cohort study. Every patient receiving a urological procedure in Paris academic urological centers during the 4 initial weeks of surgical restrictions were included. Their status was updated minimum 3 weeks after the procedure. The main outcomes were the COVID‐19 specific ICU admission and death. Statistics were mostly descriptive. The Post‐operative COVID‐19 confirmed group was compared with non‐COVID patients using Chi‐square tests for categorical and Wilcoxon test tests for continuous variables. Results During the 4‐week period, 552 patients received surgery within 8 centers. At follow‐up, 57 (10%) patients were lost. Among the 11 preoperative COVID‐19 cases, one remained in ICU, no new admission, and no death. For the non‐COVID patients, 57 (12%) developed COVID‐related symptoms; only one case (0.2%) required COVID‐19 specific ICU and 3 (0.6%) patients died of COVID‐19 after surgery. Conclusions Performing urological surgery during the COVID‐19 epidemic peak has a limited impact on ICU admissions but presents a real (0.6%) risk of specific mortality. Surgical activities should be maintained according to this risk.

Objectifs L’evaluation des resultats fonctionnels apres prise en charge des complications des bandelettes sous-uretrales (BSU) est peu connue et repose essentiellement sur des meta-analyses et des etudes a effectif reduit Les deux objectifs de cette etude etaient : d’identifier les differents tableaux cliniques amenant au diagnostic des complications de BSU et d’analyser les resultats fonctionnels apres prise en charge chirurgicale de ces complications. Methodes Nous avons realise une etude monocentrique observationnelle retrospective en incluant toutes les patientes operees d’une section ou ablation de BSU, entre decembre 2005 et octobre 2019, dans un centre de reference de pelviperineologie. Les patientes operees d’une ablation de prothese autre qu’une BSU etaient exclues. L’ensemble des interventions chirurgicales d’ablation/section de BSU ont ete realisees par un seul chirurgien urologue specialise. Les donnees suivantes ont ete recueillies et analysees : caracteristiques de la population, details de la 1re intervention recueillis d’apres le compte rendu operatoire, prise en charge chirurgicale de la complication de BSU, resultats fonctionnels : IUE et hyperactivite vesicale (HAV) a 3 mois postoperatoire. Resultats Nous avons inclus 96 patientes. Les complications de BSU prises en charges chirurgicalement etaient les suivantes : erosions vaginales (48 %), uretrales (17 %), vesicales (10 %) ; dysurie (30 %), douleur (6 %), infection (3 %). Le delai moyen avant diagnostic etait de 2 ans. Ce retard au diagnostic s’explique par une symptomatologie aspecifique et polymorphe. La prise en charge a consiste en une exerese partielle de la BSU dans 78 % des cas et une section simple dans 19 % des cas avec une faible morbidite perioperatoire. A trois mois postoperatoire, 36 patientes (53 %) presentaient une IUE dont 13 (19 %) de novo (non presente avant section/ablation) et 19 (28 %) une hyperactivite vesicale (HAV) dont 9 (13 %) de novo. Il a ete possible de reposer une 2e BSU a la moitie des patientes presentant une IUE apres section/ablation. Conclusion La presentation clinique des complications de BSU est polymorphe. Le traitement chirurgical est associe a une faible morbidite lorsqu’il est realise dans un centre de reference. En postoperatoire, la moitie des patientes presentaient une IUE et la pose d’une seconde BSU etait une option therapeutique pertinente apres une bonne evaluation.

Biomarkers guiding the neoadjuvant use of immune-checkpoint blockers (ICB) are needed for patients with localized muscle-invasive bladder cancers (MIBC). Profiling tumor and blood samples, we found that follicular helper CD4+ T cells (TFH) are among the best therapeutic targets of pembrolizumab correlating with progression-free survival. TFH were associated with tumoral CD8 and PD-L1 expression at baseline and the induction of tertiary lymphoid structures after pembrolizumab. Blood central memory TFH accumulated in tumors where they produce CXCL13, a chemokine found in the plasma of responders only. IgG4+CD38+ TFH residing in bladder tissues correlated with clinical benefit. Finally, TFH and IgG directed against urothelium-invasive Escherichia coli dictated clinical responses to pembrolizumab in three independent cohorts. The links between tumor infection and success of ICB immunomodulation should be prospectively assessed at a larger scale. Significance: In patients with bladder cancer treated with neoadjuvant pembrolizumab, E. coli–specific CXCL13 producing TFH and IgG constitute biomarkers that predict clinical benefit. Beyond its role as a biomarker, such immune responses against E. coli might be harnessed for future therapeutic strategies. This article is highlighted in the In This Issue feature, p. 2221

Purpose of review The role of a re-transurethral resection (TUR) is clearly demonstrated in T1 high-grade nonmuscle invasive bladder cancer. However, its role remains controversial for Ta high-risk tumors and the recent European guidelines stated that the second look procedure could be avoided for these patients despite harboring a high-risk of both disease recurrence and progression. We aimed to evaluate the added benefit on staging, response to bacillus Calmette-Guerin and oncological outcomes of re-TUR in patients with Ta high-grade nonmuscle invasive bladder cancer. Recent findings Overall, we identified 15 studies, including 3912 patients from which 743 harbored Ta high-grade disease. Delay between first and second TUR was ranging from 2 to 12 weeks (median 5.6 weeks). The rate of residual disease was 52.8% (range 17-67%). The rate of overall upstaging to T1 and muscle-invasive disease were 10.9 and 4.7%, respectively. Although there was a trend toward improvement of recurrence-free survival outcomes, no definitive conclusions can be drawn due to the retrospective design of the studies included. Summary Residual tumor is common after initial TUR for Ta high-grade. Re-TUR is useful in reducing the rates of residual disease, may improve staging, response to bacillus Calmette-Guerin and oncological outcomes.

Background: Patient factors associated with urinary tract cancer can be used to risk stratify patients referred with haematuria, prioritising those with a higher risk of cancer for prompt investigation. Objective: To develop a prediction model for urinary tract cancer in patients referred with haematuria. Design, setting, and participants: A prospective observational study was conducted in 10 282 patients from 110 hospitals across 26 countries, aged ≥16 yr and referred to secondary care with haematuria. Patients with a known or previous urological malignancy were excluded. Outcome measurements and statistical analysis: The primary outcomes were the presence or absence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC], and renal cancer). Mixed-effect multivariable logistic regression was performed with site and country as random effects and clinically important patient-level candidate predictors, chosen a priori, as fixed effects. Predictors were selected primarily using clinical reasoning, in addition to backward stepwise selection. Calibration and discrimination were calculated, and bootstrap validation was performed to calculate optimism. Results and limitations: The unadjusted prevalence was 17.2% (n = 1763) for bladder cancer, 1.20% (n = 123) for UTUC, and 1.00% (n = 103) for renal cancer. The final model included predictors of increased risk (visible haematuria, age, smoking history, male sex, and family history) and reduced risk (previous haematuria investigations, urinary tract infection, dysuria/suprapubic pain, anticoagulation, catheter use, and previous pelvic radiotherapy). The area under the receiver operating characteristic curve of the final model was 0.86 (95% confidence interval 0.85-0.87). The model is limited to patients without previous urological malignancy. Conclusions: This cancer prediction model is the first to consider established and novel urinary tract cancer diagnostic markers. It can be used in secondary care for risk stratifying patients and aid the clinician's decision-making process in prioritising patients for investigation. Patient summary: We have developed a tool that uses a person's characteristics to determine the risk of cancer if that person develops blood in the urine (haematuria). This can be used to help prioritise patients for further investigation.

International audience; A prognostic model based on the population of the ASSURE phase 3 trial has recently been described. The ASSURE model stratifies patients into risk groups to predict survival after surgical resection of intermediate-and high-risk localised kidney cancer. We evaluated this model in an independent cohort of 1372 patients using discrimination, calibration, and decision curve analysis. Regarding diseasefree survival, the ASSURE model showed modest discrimination (65%), miscalibration, and poor net benefit compared with the UCLA Integrated Staging System (UISS) and Leibovich 2018 models. Similarly, the ability of the ASSURE model to predict overall survival was poor in terms of discrimination (63%), with overestimation on calibration plots and a modest net benefit for the probability threshold of between 10% and 40%. Overall, our results show that the performance of the ASSURE model was less optimistic than expected, and not associated with a clear improvement in patient selection and clinical usefulness in comparison to with available models. We propose an updated version using the recalibration method, which leads to a (slight) improvement in performance but should be validated in another external population. Patient summary: The recent ASSURE model evaluates survival after surgery for nonmetastatic kidney cancer. We found no clear improvement in patient classification when we compared ASSURE with older models, so use of this model for patients with nonmetastatic kidney cancer still needs to be clarified.

To identify symptoms leading to urethral mesh exposure diagnosis, describe the surgical management and evaluate post-operative functional and urodynamic outcomes.Retrospective observational monocentric study of 15 patients treated by mid-urethral sling removal for urethral exposure, between December 2005 and February 2021, in a pelviperineology centre.Fifteen patients were included. The mean time to diagnosis of urethral exposure was 43 months. This diagnosis delay was caused by a non-specific symptomatology. Surgical management consisted of partial removal of the eroded mid-urethral sling fragment by vaginal approach in all cases, with low peri-operative morbidity. At 3 months follow-up, 87% of the patients had stress urinary incontinence vs 54% at 2 years. 13 patients had a urodynamic assessment after their mid-urethral sling removal, they all had sphincter insufficiency with a urethral closure pressure lower than 30 cm HClinical presentation of urethral erosion after mid-urethral sling is heterogeneous. Surgical management is complex; after a good preoperative evaluation, a two-step management strategy including minimally invasive mid-urethral sling removal and treatment of recurrent urinary incontinence leads to good results with 77% of patients cured. Sphincter insufficiency is one of the mechanisms that may explain the high rate of stress urinary incontinence after urethral mesh erosion surgery.

Background: The relative cardiovascular safety of gonadotropin-releasing hormone (GnRH) antagonists compared with GnRH agonists in men with prostate cancer and known atherosclerotic cardiovascular disease remains controversial. Methods: In this international, multicenter, prospective, randomized, open-label trial, men with prostate cancer and concomitant atherosclerotic cardiovascular disease were randomly assigned 1:1 to receive the GnRH antagonist degarelix or the GnRH agonist leuprolide for 12 months. The primary outcome was the time to first adjudicated major adverse cardiovascular event (composite of death, myocardial infarction, or stroke) through 12 months. Results: Because of slower-than-projected enrollment and fewer-than-projected primary outcome events, enrollment was stopped before the 900 planned participants were accrued. From May 3, 2016, to April 16, 2020, a total of 545 patients from 113 sites across 12 countries were randomly selected. Baseline characteristics were balanced between study groups. The median age was 73 years, 49.8% had localized prostate cancer; 26.3% had locally advanced disease, and 20.4% had metastatic disease. A major adverse cardiovascular event occurred in 15 (5.5%) patients assigned to degarelix and 11 (4.1%) patients assigned to leuprolide (hazard ratio, 1.28 [95% CI, 0.59–2.79]; P =0.53). Conclusions: PRONOUNCE (A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease) is the first, international, randomized clinical trial to prospectively compare the cardiovascular safety of a GnRH antagonist and a GnRH agonist in patients with prostate cancer. The study was terminated prematurely because of the smaller than planned number of participants and events, and no difference in major adverse cardiovascular events at 1 year between patients assigned to degarelix or leuprolide was observed. The relative cardiovascular safety of GnRH antagonists and agonists remains unresolved. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02663908.

Background and Objectives: Facing neoadjuvant chemotherapy followed by surgery, neoadjuvant immunotherapy is an innovative concept in localized muscle-invasive bladder cancer. Herein, we performed a review of the available and ongoing evidence supporting immune checkpoint inhibitor (ICI) administration in the early stages of bladder cancer treatment. Materials and Methods: A literature search was performed on Medline and clinical trials databases, using the terms: “bladder cancer” OR “urothelial carcinoma”, AND “neoadjuvant immunotherapy” OR “preoperative immunotherapy”. We restricted our investigations to prospective clinical trials evaluating anti-PD-(L)1 and anti-CTLA-4 monoclonal antibodies. Data on efficacy, toxicity and potential biomarkers of response were retrieved. Results: The search identified 6 ICIs that were tested in the neoadjuvant setting for localized bladder cancer—4 anti-PD-(L)1 inhibitors (Pembrolizumab, Atezolizumab, Nivolumab and Durvalumab) and 2 anti-CTLA-4 inhibitors (Ipilimumab and Tremelimumab). Most of the existing literature was based on single-arm phase 2 clinical trials that included from 23 to 143 patients. The pathological complete response rate (pCR) and pathological response rate (pRR) ranged from 31% to 46% and from 55.9% to 66%, respectively. Survival data were immature at this time. The safety profile was acceptable, with severe treatment-related adverse events ranging from 6% to 41%. Conclusions: The results of early phase trials are encouraging, and more investigations are needed to strengthen the rationale for immune checkpoint inhibitor administration in localized muscle-invasive bladder cancer.

To evaluate the prognostic role of the Bosniak classification on the long-term oncological outcomes of cystic renal cell carcinomas. In a national multicentric retrospective study, we included patients treated surgically for localized cystic RCC from 2000 to 2010. Patients with a follow-up of less than 4 years, benign tumors, and ablative treatments were excluded. The primary outcome was disease-free survival. 152 patients met the inclusion criteria: Bosniak II (6%), III (53%), IV (41%), with a median follow-up of 61 (12–179) months. Characteristics of the population and the tumors were [median, (min–max)] age 57 (25–84) years old, tumor size 43 mm (20–280), RENAL score 7 (4–12), PADUA score 8 (5–14). Treatments were 55% partial nephrectomy, 45% radical nephrectomy, 74% open surgery, and 26% laparoscopy. In pathological report, cystic RCC were mainly of low grade (1–2, 77%) and low stage (pT1, 81%). The two main histological subtypes were conventional (56%) and papillary (23%) RCC. Staging at presentation and histological characteristics were similar between Bosniak III and IV, except for high grade which was more common in Bosniak IV (12 vs 36%, p

To date, transurethral resection of bladder tumor (TURBT) remains the gold standard of staging urothelial cancer of the bladder and treating non-muscle invasive bladder cancer (NMIBC). The primary goal of the procedure includes a proper diagnosis, correct staging, and removal all lesions. Herein, we discuss major contemporary surgical and technical aspects of including en bloc resection, bipolar and laser resection as well as quality control of TURBT.

Most of low grade (LG) bladder tumors will experience disease recurrence and very few of them (

Context Management of locally recurrent renal cancer is complex. Objective In this systematic review we analyse the available literature on the management of local renal cancer recurrence. Evidence acquisition A systematic search (PubMed, Web of Science, CINAHL, Clinical Trials, and Scopus) of English literature from 2000 to 2017 was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Evidence synthesis The search identified 1838 articles. Of those, 36 were included in the evidence synthesis. The majority of the studies identified were retrospective and not controlled. Local recurrence after thermal ablation (TA) may be managed with repeat TA. Alternatively, salvage nephrectomy is possible. However, a higher rate of complications should be expected than after primary nephrectomy. Salvage nephrectomy and TA represent treatment options for local recurrence after partial nephrectomy. Local retroperitoneal recurrence after radical nephrectomy is ideally treated with surgical resection, for which minimally invasive approaches might be applicable to select patients. For large recurrences, addition of intraoperative radiation may improve local control. Local tumour destruction appears to be more beneficial than systemic therapy alone for local recurrences. Conclusions Management of local renal cancer relapse varies according to the clinical course and prior treatments. The available data are mainly limited to noncontrolled retrospective series. After nephron-sparing treatment, TA represents an effective treatment with low morbidity. For local recurrence after radical nephrectomy, the low-level evidence available suggests superiority of surgical excision relative to systemic therapy or best supportive care. As a consequence, surgery should be prioritised when feasible and applicable. Patient summary In renal cell cancer, the occurrence and management of local recurrence depend on the initial treatment. This cancer is a disease with a highly variable clinical course. After initial organ-sparing treatment, thermal ablation offers good cancer control and low rates of complications. For recurrence after radical nephrectomy, surgical excision seems to provide the best long-term cancer control and it is superior to medical therapy alone.

Background: A non-negligible proportion of individuals diagnosed with cT1 renal cell carcinoma (RCC) are upstaged to pT3a at final pathology. Few data on oncological outcomes for these patients are available to determine whether partial nephrectomy (PN) might jeopardise cancer control. Objective: To assess, within an international multi-institutional collaboration, whether PN might undermine cancer control relative to radical nephrectomy (RN) in RCC patients with unexpected pT3a disease. Design, setting, and participants: International multi-institutional collaboration including patients with cT1abN0M0-pT3a RCC. Intervention: PN or RN. Outcome measurements and statistical analysis: We used Kaplan-Meier analyses, before and after propensity-score matching, to evaluate differences in metastatic progression (MP) and cancer-specific mortality (CSM) rates during follow-up. Univariable and multivariable Cox regression analyses were used to assess predictors of MP and CSM. Results and limitations: Overall, 309 patients with cT1abN0M0 RCC (cT1aN0M0, n = 107, 34.6%; cT1bN0M0, n = 202, 65.4%) had pT3a disease according to final pathology. Patients were treated with either PN (n = 71, 23%) or RN (n = 238, 77%). MP at 1, 2, and 5 yr was detected in 9.1%, 13.3%, and 24.1% of patients, respectively. CSM was 3.5%, 10.7%, and 18.4% at 1, 2, and 5 yr, respectively. After matching, no difference in terms of MP or CSM was observed between the PN and RN cohorts (both p>0.3). On multivariable analysis, type of surgery (PN vs RN) was not an independent predictor of either MP (p = 0.3) or CSM (p = 0.4). Limitations include the retrospective design. Conclusions: In patients with unexpected pT3a RCC at final pathology, PN does not appear to jeopardise cancer control with regard to MP and CSM. Patient summary: Cancer control is similar between patients treated with removal of the entire kidney and those with only partial removal, even if the final histology examination demonstrates a tumour that is unexpectedly not confined within the kidney. Partial nephrectomy does not undermine cancer control when unexpected pT3a renal cancer is identified at final pathology.

Introduction: Immunotherapy is changing the way we think about and treat urothelial carcinoma (UC). The PD-1/PD-L1 pathway inhibition has shown robust efficacy, associated with an acceptable toxicity profile, in patients with locally advanced and metastatic unresectable disease, addressing a high decades-old unmet medical need. Material and methods: Using the Pubmed database, we conducted a literature review for English written published articles up to June 2020. The highest available evidence for the immunotherapy treatment of UC with ICIs were evaluated. The leading phase one, two and three clinical trials were considered for inclusion (n = 12). Patient’s data were extracted from studies depicting the UTUC subpopulation. Results: Two monoclonal antibodies targeting PD-1 (pembrolizumab and nivolumab) and three to its ligand PD-L1 (atezolizumab, avelumab, and durvalumab) have obtained US FDA and EMA approval for the second-line treatment of platinum-pretreated patients, between 2016 and 2019. Atezolizumab and Pembrolizumab are even currently approved in the first-line setting for cisplatin ineligible patients, with PD-L1- positive tumor. The neoadjuvant scenario in localized high-risk disease is still evolving, with the first data available to date limited to the muscle-invasive bladder carcinoma. The management of patients with upper tract urothelial carcinoma (UTUC: renal pelvis and ureters) is complicated by the lack of specific high-level evidence, due to the rarity of the disease. No published studies addressing immunotherapy in UTUC patients only are available. The largest clinical trials aimed at UC patients, regardless of the upper or lower location of the primary tumor, have enrolled a minority of patients with UTUC, providing the data on which our current knowledge is based. However, targeted scientific efforts are needed to improve our level of care. Conclusions: This review summarizes the main currently available evidence on the use of the PD-1/PD-L1 pathway inhibition with reference to patients presenting with UTUC.

Purpose: To investigate the natural history and follow-up after kidney tumor treatment of Von Hippel-Lindau (VHL) patients. Materials and methods: A multi-institutional European consortium of patients with VHL syndrome included 96 non-metastatic patients treated at 9 urological departments (1987–2018). Descriptive and survival analyses were performed. Results and limitations: Median age at VHL diagnosis was 34years (IQR 25–43). Two patients (2.1%) showed only renal manifestations at VHL diagnosis. Concomitant involvement of Central Nervous System (CNS) vs. pancreas vs. eyes vs. adrenal gland vs. others were present in 60.4 vs. 68.7 vs. 30.2 vs. 15.6 vs. 15.6% of patients, respectively. 45% of patients had both CNS and pancreatic diseases alongside kidney. The median interval between VHL diagnosis and renal cancer treatment resulted 79months (IQR 0–132), and median index tumor size leading to treatment was 35.5mm (IQR 28–60). Of resected malignant tumours, 73% were low grade. Of high-grade tumors, 61.1% were large > 4cm. With a median follow-up of 8years, clinical renal progression rate was 11.7% and 29.3% at 5 and 10years, respectively. Overall mortality was 4% and 7.5% at 5 and 10years, respectively. During the follow-up, 50% of patients did not receive a second active renal treatment. Finally, 25.3% of patients had CKD at last follow-up. Conclusions: Mean period between VHL diagnosis and renal cancer detection is roughly three years, with significant variability. Although, most renal tumors are small low-grade, clinical progression and mortality are not negligible. Moreover, kidney function represents a key issue in VHL patients.

Non-muscle invasive bladder cancer (NMIBC) is a highly heterogeneous disease that hides classes of patients who behave significantly differently under a favorable overall prognosis facade. Individual risk stratification and good decision making improve the patient outcomes. To date, radical cystectomy remains the treatment of choice in particularly aggressive subsets of disease, also due to the lack of proven alternative bladder-sparing strategies.Cancer immunotherapy, by inhibiting the PD-1/PD-L1axis, has shown durable efficacy in the treatment of advanced and metastatic unresectable urothelial carcinoma, and is studied with great interest in early disease settings. The updated data of the KEYNOTE-057 study have recently promoted the United States (US) Food and Drug Administration (FDA) approval of pembrolizumabin patients with CIS-containing BCG-unresponsive NMIBC. This significant step forward paves the way to a new window of therapeutic opportunities, while underlining new needs and questions to be addressed.El cáncer de vejiga no músculo-invasivoes una enfermedad bastante heterogénea que incluye varias clases de pacientes diferentes que se comportan de forma diferente en términos de pronóstico. La clasificación individualizada de riesgo y una buena herramienta de decisión nos permite mejorar los resultados de estos pacientes. Hasta la actualidad, la cistectomía radical sigue siendo la alternativa de tratamiento en un subgrupo de pacientes con tumores altamente agresivos debido a la falta de tratamientos alternativos para preservar la vejiga. La inmunoterapia en cáncer, a través de la inhibición del eje PD-1/PD-L1, ha demostrado una eficacia duradera en el tratamiento del cáncer de vejiga avanzado y metastático. Además se esta estudiando con mucho interés en la fase temprana de la enfermedad. Los resultados actualizados de KEYNOTE-057 han proporcionado en Estados Unidos la aprobación de la FDA depembrolizumab en pacientes con CIS no-respondedores a BCG por cáncer de vejiga no músculo invasivo. Este es un paso importante que nos lleva hacia una nueva ventana de oportunidades, mientras nuevas necesidades y preguntas están esperando respuesta.

Background Data comparing percutaneous ablation (PCA) and surgical resection (SR) for an isolated local recurrence (LR) following partial nephrectomy (PN) for renal cell carcinoma (RCC) are lacking. Objective To examine the outcomes between PCA and SR for an isolated LR following PN for RCC. Design, setting, and participants Patients who underwent PN for RCC and developed an LR between 2013 and 2019 were included. An LR was defined as the appearance of a mass in contact with the resection bed or the development of a tumor in the same region of the homolateral kidney as the original site. Intervention PCA or SR. Outcome measurements and statistical analysis To achieve balance in baseline characteristics, we used inverse probability of treatment weighting (IPTW) based on propensity to receive treatment. Oncological outcomes, complications, and renal function were evaluated between groups using logistic, linear, and Cox proportional hazard regression models. Results and limitations A total of 81 patients with an isolated LR were included (PCA: 42; SR: 39). The median follow-up was 23 mo. After adjustment, excellent balance was achieved for the majority of propensity score variables. In IPTW analysis, PCA was associated with a lower risk of postoperative complications (odds ratio = 0.22; p = 0.006) and a smaller change in eGFR (beta = −16.18; p = 0.001). There were no significant differences in the risk of disease recurrence (hazard ratio [HR] = 0.72; p = 0.61), new LR (HR = 1.51; p = 0.59), and distant metastasis (HR = 0.19; p = 0.09). Limitations include the sample size and unmeasured confounding factors. Conclusions Our results suggest that PCA provides comparable oncological outcomes to repeat surgery with fewer complications and better renal function preservation for the management of an LR after PN. Patient summary This report shows that percutaneous ablation can be used for treating a local recurrence of renal cell carcinoma after partial nephrectomy, without significantly compromising cancer control.

To investigate the association of adherent perinephric fat (APF) with perioperative outcomes, we conducted a systematic review and meta-analysis of the literature to clarify the impact of APF in patients undergoing partial nephrectomy. A systematic literature search using the Medline, Scopus, and Cochrane databases was performed in April 2019 and updated in November 2019 to identify studies investigating the effect of APF on perioperative outcomes in patients treated with partial nephrectomy with the aim of evaluating its impact on intraoperative, postoperative and oncological outcomes. The Newcastle–Ottawa Scale (NOS) was used to assess the quality of the included studies. A total of 1534 patients in nine nonrandomized, observational studies met our inclusion criteria. Patients with APF were significantly older (p = 0.0001), had a higher BMI (p = 0.0001) and were predominately male (p = 0.003). APF was associated with a higher operative time (p = 0.001) and higher blood loss (p = 0.002). No significant impact of APF was found in terms of postoperative complications, positive margins or length of stay. APF was also found to be associated with malignant renal histology of RCC on final pathology (p = 0.005). APF was associated with some adverse perioperative outcomes, especially a prolonged operating time and higher blood loss. In addition, APF was also associated with underlying renal malignancy, but the precise causal mechanism requires further exploration.

Background Despite being the most frequent renal fusion anomaly, tumors arising from horseshoe kidneys (HSKs) are extremely rare and management guidance is lacking. Objective To evaluate the perioperative, oncological, and functional outcomes of surgically treated HSK tumors. Design, setting, and participants A retrospective, multicenter cohort study of 43 HSK tumors in 40 patients was conducted, and technical description of the surgical approach has been provided. Surgical procedure Surgical resection of renal tumors arising from HSKs was performed either via open surgery or via minimally invasive surgery (MIS). Measurements We analyzed patient and tumor characteristics as well as surgical technique, and functional and oncological outcomes. Results and limitations Eight patients were treated by MIS and 32 by open surgery. One patient (2.5%) experienced an intraoperative complication and 13 patients (32.5%) experienced postoperative complications, of which three (7.5%) were Clavien-Dindo ≥3 complications. Surgical margins were positive in two tumors (4.7%). The most frequent histology was clear-cell renal cell carcinoma (46.5%). The median follow-up was 51 (interquartile range [IQR] 17–73) mo. The 5-yr overall, cancer-specific, and recurrence-free survival rates were 81.2%, 86.8%, and 83.1%, respectively. The percent decreases in estimated glomerular filtration rate at discharge and the last follow-up were 15% (IQR 4–26%) and 17% (IQR 1–31%), respectively. Limitations include the cohort's retrospective nature, heterogeneity, and small sample size. Conclusions Surgical management of tumors in HSKs can be approached via both open surgery and MIS, with maximal preservation of functional renal parenchyma. In this cohort, rates of complications, positive surgical margins, and renal functional decrease were acceptable, considering the anatomical complexity of these kidneys and tumors. These tumors display great variation in histological subtypes. Meticulous presurgical planning, taking advantage of advanced imaging techniques, can aid in achieving good outcomes. Patient summary We evaluated the surgical management of renal tumors in horseshoe kidneys, which are very rare. Although these procedures are highly complex, outcomes are acceptable. Modern imaging techniques are often required in presurgical planning.

Purpose To assess whether progressive and primary muscle invasive bladder cancer (MIBC) have different prognosis after radical cystectomy or not. To date only a few data are available on this topic with conflicting results. Further studies on large cohort are needed to clarify these outcomes that may influence bladder cancer management for these patients. Material and methods A multicentre retrospective study was conducted on patient treated for MIBC at 5 centres between 2005 and 2015 by radical cystectomy. Patients’ outcomes were compared between patients with primary MIBC vs. progressive MIBC subsequent to a history of non-muscle invasive bladder cancer (NMIBC). Results A total of 1197 patients were included. Median (IQ) age was 65 (58–72) years and median follow-up was 65 months. Baseline characteristics were similar between the groups as well as the Tumour pT stage, N status and positive surgical margins. Patients with progressive MIBC had worse overall survival (OS) (hazard ratio [HR] 1.36, [95%CI 1.10–1.76]; P = 0.004), cancer specific survival (CSS) (HR 1.41 [1.13–1.78]; P = 0.002), and recurrence-free survival (RFS) (HR 1.21 [1.01–1.49]; P = 0.05). Pathological stage ≥pT3, positive surgical margins, and positive lymph nodes status (pN+) were also found as predictors of OS, CSS, and RFS. Conclusions Our results suggest that patient having a progressive BC have a worse prognosis in terms of OS, PFS, and CSS than patient with primary disease. These 2 groups may require different management and patients with high risk NMIBC should be assessed properly to avoid progression and be offered early cystectomy.