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Contains fulltext : 294430.pdf (Publisher’s version ) (Open Access) BACKGROUND: Ta grade 3 (G3) non-muscle-invasive bladder cancer (NMIBC) is a relatively rare diagnosis with an ambiguous character owing to the presence of an aggressive G3 component together with the lower malignant potential of the Ta component. The European Association of Urology (EAU) NMIBC guidelines recently changed the risk stratification for Ta G3 from high risk to intermediate, high, or very high risk. However, prognostic studies on Ta G3 carcinomas are limited and inconclusive. OBJECTIVE: To evaluate the prognostic value of categorizing Ta G3 compared to Ta G2 and T1 G3 carcinomas. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data for 5170 primary Ta-T1 bladder tumors from 17 hospitals were analyzed. Transurethral resection of the tumor was performed between 1990 and 2018. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Time to recurrence and time to progression were analyzed using cumulative incidence functions, log-rank tests, and multivariable Cox-regression models with interaction terms stratified by institution. RESULTS AND LIMITATIONS: Ta G3 represented 7.5% (387/5170) of Ta-T1 carcinomas of which 42% were classified as intermediate risk. Time to recurrence did not differ between Ta G3 and Ta G2 (p = 0.9) or T1 G3 (p = 0.4). Progression at 5 yr occurred for 3.6% (95% confidence interval [CI] 2.7-4.8%) of Ta G2, 13% (95% CI 9.3-17%) of Ta G3, and 20% (95% CI 17-23%) of T1 G3 carcinomas. Time to progression for Ta G3 was shorter than for Ta G2 (p

The effect of ERAS protocols in a population of radical cystectomy (RC) patients fit for neoadjuvant chemotherapy has not been specifically explored.To compare perioperative outcomes of open RC according to the application of an ERAS protocol in a population of patients treated by cisplatin-based NAC.All consecutive patients treated by NAC and RC between 2016 and 2019 were included. The ERAS pathway was implemented in June 2018 and followed the EAU recommendations. All data were prospectively collected. Patients' characteristics, operative outcomes, length of stay (LOS), complication rate according to Clavien-Dindo and pathological results were compared between pre- and post-ERAS. Statistical analysis was performed using R.In total, 79 patients were included, 29 in the ERAS group and 50 in the non-ERAS group. A median number of 19 out of 22 ERAS criteria were followed. Mean number of NAC cycles was 4.45 vs. 4.79 in the pre- and post-ERAS groups respectively (P=0.24). Median time between NAC and RC was 3.8months. Thirty-eight percent vs. 48% of patients received an ileal neobladder in the pre- and post-ERAS group respectively (P=0.51). No differences were observed regarding operative time, blood loss or operative transfusion rates. LOS was drastically reduced in the ERAS period (18.94 vs. 12.10days, P0.001) as well as major (Clavien 2) complications rate (65% vs. 28%, P=0.004).ERAS drastically reduced the LOS and the rate of high-grade complications and can be effectively applied to patients receiving NAC without delaying RC.

Context The European Association of Urology (EAU) has released an updated version of the guidelines on non–muscle-invasive bladder cancer (NMIBC). Objective To present the 2021 EAU guidelines on NMIBC. Evidence acquisition A broad and comprehensive scoping exercise covering all areas of the NMIBC guidelines since the 2020 version was performed. Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries. Previous guidelines were updated, and the level of evidence and grade of recommendation were assigned. Evidence synthesis Tumours staged as Ta, T1 and carcinoma in situ (CIS) are grouped under the heading of NMIBC. Diagnosis depends on cystoscopy and histological evaluation of tissue obtained via transurethral resection of the bladder (TURB) for papillary tumours or via multiple bladder biopsies for CIS. For papillary lesions, a complete TURB is essential for the patient’s prognosis and correct diagnosis. In cases for which the initial resection is incomplete, there is no muscle in the specimen, or a T1 tumour is detected, a second TURB should be performed within 2–6 wk. The risk of progression may be estimated for individual patients using the 2021 EAU scoring model. On the basis of their individual risk of progression, patients are stratified as having low, intermediate, high, or very high risk, which is pivotal to recommending adjuvant treatment. For patients with tumours presumed to be at low risk and for small papillary recurrences detected more than 1 yr after a previous TURB, one immediate chemotherapy instillation is recommended. Patients with an intermediate-risk tumour should receive 1 yr of full-dose intravesical bacillus Calmette-Guerin (BCG) immunotherapy or instillations of chemotherapy for a maximum of 1 yr. For patients with high-risk tumours, full-dose intravesical BCG for 1–3 yr is indicated. For patients at very high risk of tumour progression, immediate radical cystectomy should be considered. Cystectomy is also recommended for BCG-unresponsive tumours. The extended version of the guidelines is available on the EAU website at https://uroweb.org/guideline/non-muscle-invasive-bladder-cancer/ . Conclusions These abridged EAU guidelines present updated information on the diagnosis and treatment of NMIBC for incorporation into clinical practice. Patient summary The European Association of Urology has released updated guidelines on the classification, risk factors, diagnosis, prognostic factors, and treatment of non–muscle-invasive bladder cancer. The recommendations are based on the literature up to 2020, with emphasis on the highest level of evidence. Classification of patients as having low, intermediate, or and high risk is essential in deciding on suitable treatment. Surgical removal of the bladder should be considered for tumours that do not respond to bacillus Calmette-Guerin (BCG) treatment and tumours with the highest risk of progression.

Supplementary methods, tables and figures

Background: Increasing evidence points to the role of tumor immunologic environment on urothelial bladder cancer prognosis. This effect might be partly dependent on the host genetic context. We evaluated the association of SNPs in inflammation-related genes with non–muscle-invasive bladder cancer (NMIBC) risk-of-recurrence and risk-of-progression.Methods: We considered 822 NMIBC included in the SBC/EPICURO Study followed-up >10 years. We selected 1,679 SNPs belonging to 251 inflammatory genes. The association of SNPs with risk-of-recurrence and risk-of-progression was assessed using Cox regression single-marker (SMM) and multimarker methods (MMM) Bayes A and Bayesian LASSO. Discriminative abilities of the models were calculated using the c index and validated with bootstrap cross-validation procedures.Results: While no SNP was found to be associated with risk-of-recurrence using SMM, three SNPs in TNIP1, CD5, and JAK3 showed very strong association with posterior probabilities >90% using MMM. Regarding risk-of-progression, one SNP in CD3G was significantly associated using SMM (HR, 2.69; P = 1.55 × 10−5) and two SNPs in MASP1 and AIRE, showed a posterior probability ≥80% with MMM. Validated discriminative abilities of the models without and with the SNPs were 58.4% versus 60.5% and 72.1% versus 72.8% for risk-of-recurrence and risk-of-progression, respectively.Conclusions: Using innovative analytic approaches, we demonstrated that SNPs in inflammatory-related genes were associated with NMIBC prognosis and that they improve the discriminative ability of prognostic clinical models for NMIBC.Impact: This study provides proof of concept for the joint effect of genetic variants in improving the discriminative ability of clinical prognostic models. The approach may be extended to other diseases. Cancer Epidemiol Biomarkers Prev; 25(7); 1144–50. ©2016 AACR.

Context: Bladder recurrences have been reported in 22–47% of patients after surgery for upper urinary tract urothelial carcinoma (UTUC). This collaborative review focuses on risk factors for and treatment strategies to reduce bladder recurrences after upper tract surgery for UTUC. Objective: To review the current evidence on risk factors and treatment strategies for intravesical recurrence (IVR) after upper tract surgery for UTUC. Evidence acquisition: This collaborative review is based on a literature search of PubMed/Medline, Embase, Cochrane Library, and currently available guidelines on UTUC. Relevant papers on bladder recurrence (etiology, risk factors, and management) after upper tract surgery were selected. Special attention has been paid to (1) the genetic background of bladder recurrences, (2) bladder recurrences after ureterorenoscopy (URS) with or without a biopsy, and (3) postoperative or adjuvant intravesical instillations. The literature search was performed in September 2022. Evidence synthesis: Recent evidence supports the hypothesis that bladder recurrences after upper tract surgery for UTUC are often clonally related. Clinicopathologic risk factors (patient, tumor, and treatment related) have been identified for bladder recurrences after UTUC diagnosis. Specifically, the use of diagnostic ureteroscopy before radical nephroureterectomy (RNU) is associated with an increased risk of bladder recurrences. Further, a recent retrospective study suggests that performing a biopsy during ureteroscopy may further worsen IVR (no URS: 15.0%; URS without biopsy: 18.4%; URS with biopsy: 21.9%). Meanwhile, a single postoperative instillation of intravesical chemotherapy has been shown to be associated with a reduced bladder recurrence risk after RNU compared with no instillation (hazard ratio 0.51, 95% confidence interval 0.32–0.82). Currently, there are no data on the value of a single postoperative intravesical instillation after ureteroscopy. Conclusions: Although based on limited retrospective data, performing URS seems to be associated with a higher risk of bladder recurrences. Future studies are warranted to assess the influence of other surgical factors as well as the role of URS biopsy or immediate postoperative intravesical chemotherapy after URS for UTUC. Patient summary: In this paper, we review recent findings on bladder recurrences after upper tract surgery for upper urinary tract urothelial carcinoma.

CIS of the bladder is associated with a high risk of progression. In the case of BCG failure, radical cystectomy should be performed. For patients who refuse or are ineligible, bladder-sparing alternatives are evaluated. This study aims to investigate the efficacy of Hyperthermic IntraVesical Chemotherapy (HIVEC) depending on the presence or absence of CIS. This retrospective, multicenter study was conducted between 2016 and 2021. Patients with non-muscle-invasive bladder cancer (NMIBC) with BCG failure received 6–8 adjuvant instillations of HIVEC. The co-primary endpoints were recurrence-free survival (RFS) and progression-free survival (PFS). A total of 116 consecutive patients met our inclusion criteria of whom 36 had concomitant CIS. The 2-year RFS rate was 19.9% and 43.7% in patients with and without CIS, respectively (p = 0.52). Fifteen patients (12.9%) experienced progression to muscle-invasive bladder cancer with no significant difference between patients with and without CIS (2-year PFS rate = 71.8% vs. 88.8%, p = 0.32). In multivariate analysis, CIS was not a significant prognostic factor in terms of recurrence or progression. In conclusion, CIS may not be considered a contraindication to HIVEC, as there is no significant association between CIS and the risk of progression or recurrence after treatment.

To describe the clinico-pathological characteristics of NMIBC treated in metropolitan France over one year when BCG was subject to a national quota. In the context of recurrent shortages of intravesical BCG for non-muscle-invasive bladder cancer (NMIBC), it is interesting to document the real-life indications for adjuvant treatment.Between February 2021 and February 2022, the French National Agency for the Safety of Medicines (ANSM) asked the French Association of Urology (AFU) to propose a science-based quota solution for BCG using a clinical score. The ANSM then asked the distributor of the drug, MEDAC, to collect the scores for all patients for whom BCG was requested by healthcare institutions and to prioritise the requests for patients with the highest scores. Tumour stage, grade, size, number, time to recurrence, carcinoma in situ, age, accessibility of alternative treatments (total cystectomy, radio-chemotherapy, thermo-chemotherapy) and BCG treatment progress (initiation or maintenance) were documented for each intravesical BCG prescription. A descriptive analysis of the data collected during the quota year was performed.During the 1-year quota, 25 878 requests for BCG were made for 19 024 patients, 60.5% of whom were ≥70-years-old. Requests for induction and maintenance treatment accounted for 12 704 (49.1%) and 13 174 (50.9%) of prescriptions, respectively. NMIBCs treated with BCG maintenance therapy were more frequently high-risk NMIBCs (91.7% vs. 90.2%, p0.0001) than NMIBCs for which induction therapy was requested. The number of cases of NMIBC leading to BCG adjuvant treatment was estimated at 12 704 cases/66 062 188 inhabitants over 1 year in metropolitan France.Our data suggest that the incidence of NMIBC at high-risk of recurrence and progression is underestimated in reference epidemiological studies. These results should help to better define future care needs.

Upper urinary tract urothelial carcinoma (UTUC) is an uncommon disease and its gold-standard treatment is radical nephroureterectomy (RNU). Distal ureterectomy (DU) might be an alternative for tumors of the distal ureter but its indications remain unclear. Here, we aimed to evaluate the oncological outcomes of DU for UTUC of the pelvic ureter. We performed a multicenter retrospective analysis of patients with UTUC who underwent DU. The primary endpoint was 5-year cancer-specific survival (CSS), followed by overall survival (OS), intravesical recurrence-free (IVR) and homolateral urinary tract recurrence-free (HUR) survivals as secondary endpoints. Univariate and multivariate Cox regressions were performed to assess factors associated with outcomes. 155 patients were included, 91% of which were high-risk. 5-year CSS was 84.4%, OS was 71.9%, IVR-free survival was 43.6% and HUR-free survival was 74.4%. Multifocality, high grade and tumor size were the most significant predictors of survival endpoints. Of note, neither hydronephrosis nor pre-operative diagnostic ureteroscopy/JJ stent were associated with any of the endpoints. Perioperative morbidity was minimal. In conclusion, DU stands as a possible alternative to RNU for UTUC of the pelvic ureter. Close monitoring is mandatory due to the high risk of recurrence in the remaining urinary tract.

Item does not contain fulltext BACKGROUND: The pathological existence and clinical consequence of stage T1 grade 1 (T1G1) bladder cancer are the subject of debate. Even though the diagnosis of T1G1 is controversial, several reports have consistently found a prevalence of 2-6% G1 in their T1 series. However, it remains unclear if T1G1 carcinomas have added value as a separate category to predict prognosis within the non-muscle-invasive bladder cancer (NMIBC) spectrum. OBJECTIVE: To evaluate the prognostic value of T1G1 carcinomas compared to TaG1 and T1G2 carcinomas within the NMIBC spectrum. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data for 5170 primary Ta and T1 bladder tumors from 17 hospitals in Europe and Canada were analyzed. Transurethral resection (TUR) was performed between 1990 and 2018. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Time to recurrence and progression were analyzed using cumulative incidence functions, log-rank tests, and multivariable Cox regression models stratified by institution. RESULTS AND LIMITATIONS: T1G1 represented 1.9% (99/5170) of all carcinomas and 5.3% (99/1859) of T1 carcinomas. According to primary TUR dates, the proportion of T1G1 varied between 0.9% and 3.5% per year, with similar percentages in the early and later calendar years. We found no difference in time to recurrence between T1G1 and TaG1 (p = 0.91) or between T1G1 and T1G2 (p = 0.30). Time to progression significantly differed between TaG1 and T1G1 (p < 0.001) but not between T1G1 and T1G2 (p = 0.30). Multivariable analyses for recurrence and progression showed similar results. CONCLUSIONS: The relative prevalence of T1G1 diagnosis was low and remained constant over the past three decades. Time to recurrence of T1G1 NMIBC was comparable to that for other stage/grade NMIBC combinations. Time to progression of T1G1 NMIBC was comparable to that for T1G2 but not for TaG1, suggesting that treatment and surveillance of T1G1 carcinomas should be more like the approaches for T1G2 NMIBC in accordance with the intermediate and/or high risk categories of the European Association of Urology NMIBC guidelines. PATIENT SUMMARY: Although rare, stage T1 grade 1 (T1G1) bladder cancer is still diagnosed in daily clinical practice. Using individual patient data from 17 centers in Europe and Canada, we found that time to progression of T1G1 cancer was comparable to that for T1G2 but not TaG1 cancer. Therefore, our results suggest that primary T1G1 bladder cancers should be managed with more aggressive treatment and more frequent follow-up than for low-risk bladder cancer.

Riassunto La cistectomia totale accompagnata da una dissecazione linfonodale e il trattamento standard per i tumori della vescica che invadono il muscolo. E una procedura semplice, a patto di comprendere e rispettare l’anatomia chirurgica del bacino. Includere i pazienti nei protocolli di riabilitazione migliorata dopo l’intervento chirurgico (RAAC) riduce la morbilita di questa procedura. La tecnica chirurgica deve essere quanto piu standardizzata possibile al fine di ridurre al massimo il tempo operatorio e la perdita di sangue. Una conoscenza approfondita dell’anatomia della prostata e dell’uretra e essenziale per preservare l’uretra in vista della sostituzione della vescica. L’utilizzo di sistemi di termofusione tissutale ha rivoluzionato la dissecazione e l’emostasi dei peduncoli vascolari vescicali e prostatici in assenza di conservazione nervosa. La dissecazione linfonodale e una parte fondamentale dell’operazione e deve rispettare i limiti anatomici della dissecazione estesa. L’uretrectomia non e di routine, ma deve essere presa in considerazione in caso di tumore esteso all’uretra prostatica. La tecnica per via prepubica evita un’ulteriore incisione perineale e riduce la morbilita.

Major interest lies in the evaluation of immune infiltrate in bladder cancer. CD8+ cytotoxic lymphocytes are key effectors of adaptive immune response.The aims of the study were to set up a standardized methodology for CD8+ lymphocytes estimation in NMIBC and investigate how intra-tumoral heterogeneity influences CD8+ immune infiltrate.We considered 995 NMIBC included in the Spanish Bladder Cancer (SBC)/EPICURO Study. Duplicate 0.6mm TMA spots and paired full sections (FS) for 50 selected cases were double stained with anti-pan cytokeratin antibody and anti-CD8 antibody. Slides were digitalized and CD8+ cells were automatically counted after tissue recognition (tumor vs stroma). Spatial heterogeneity was assessed and a resampling strategy was applied to estimate the proper number of 0.6mm TMA spots providing an adequate CD8+ cell estimate. Association between CD8+ count and expression of urothelial differentiation markers was estimated. Cox regression models were performed to assess association between CD8+ cell count and risk of recurrence and progression.Microscopic examination of full sections showed spatial heterogeneity for CD8+ infiltrates. Simulation analyses demonstrated that 5 TMA regions provided a correct sampling of tumor and stromal compartments in Ta while 2 and 6 TMA regions were necessary in T1, respectively. CD8+ cells infiltration was associated with stage, regardless of the histological compartment analyzed (median CD8+ /mmDifferences identified between Ta and T1 tumours supported the hypothesis that rigorous efforts should be placed in proper study design. These results provide a new framework to investigate microenvironment complexity in bladder cancer.

Endoscopic access and treatment of bleeding upper urinary tract urothelial carcinomas (UTUCS) is sometimes difficult and inefficient as resection and/or laser coagulation are often incomplete. We report two cases of successful cryoablation of bleeding UTUCs.This study evaluated an adjunctive method in using cryoablation as a hemostatic technique. Cryoprobes were inserted inside the affected calices and a standard renal cryoablation protocol was used. Track ablation was performed during the pullback of the cryoprobes to prevent tumor seeding and bleeding.Cryoablation of the bleeding upper urinary tract tumors allowed to efficiently resolve macrohematuria in both patients and to provide prolonged remission in one patient.Taking advantage of the microcirculatory stasis and the hemostatic properties of cryoablation, we achieved palliative cessation of refractory macrohematuria while sparing nephrons, without the need for renal embolization in patients with bleeding UTUCs.

Resumen La cistectomia total asociada a un vaciamiento ganglionar es el tratamiento de referencia de los tumores de vejiga con invasion muscular. Se trata de una intervencion simple, siempre que se conozca y se respete la anatomia quirurgica de la pelvis. La inclusion de los pacientes en protocolos de rehabilitacion mejorada posquirurgica (RMPQ) permite reducir la morbilidad de este procedimiento. La tecnica quirurgica debe ser lo mas estandarizada posible para reducir al maximo la duracion de la intervencion y la perdida de sangre. El conocimiento perfecto de la anatomia prostatica y uretral es indispensable para la preservacion de la uretra con vistas a un reemplazo vesical. La utilizacion de sistemas de termofusion tisular ha revolucionado la diseccion y la hemostasia de los pediculos vasculares vesicales y prostaticos en ausencia de preservacion nerviosa. El vaciamiento ganglionar es un tiempo fundamental de la intervencion y debe respetar los limites anatomicos del vaciamiento ampliado. La uretrectomia no se realiza de forma sistematica, pero debe plantearse en los tumores ampliados a la uretra prostatica. La tecnica por via prepubica evita una incision perineal suplementaria y disminuye la morbilidad.

International audience; Objectives: The increasing incidence of fluoroquinolones (FQ) resistance may lower its efficacy in preventing UTI following transrectal ultrasound-guided prostate biopsy (TRUS-PB). We assessed the efficacy and safety of FQ and fosfomycin-trometamol (FT) in patients undergoing TRUS-PB.Methods: A prospective observational study was conducted between April 2017 and June 2019 and enrolled men undergoing TRUS-PB and receiving a single-dose of FQ (FQ-arm) or FT (FT-arm) for UTI prophylaxis per physician's choice. The primary efficacy endpoint was self-reported TRUS-PB UTI. We assessed baseline factors associated with UTI with logistic regression.Results: A total of 222 men were enrolled, 141/222 (64%) received FQ, and 81/222 (36%) FT. The median age was 67.6 years [IQR, 61.4-72.1] and the Charlson score was 3 [IQR, 3-5]. The overall incidence of self-reported TRUS-PB UTI was 12% (24/197, (95%CI, 8%-17%)): 15% (17/116, (95% CI, 10%-17%)) in FQ-arm, versus 9% (7/81, 95% CI (5%-13%)) in FT-arm (RR = 0.55 (95% CI, 0.22-1.40), p-value = 0.209). No baseline characteristic was significantly associated with TRUS-PB UTI. Safety was similar between the arms: the rate of the reported adverse event was 31% (36/116, (95% CI, 25%-37%) in the FQ-arm versus 36% (28/81, (95% CI, 28%-41%)) in the FT-arm (RR = 1.17 (95% CI, 0.64-2.15), p = 0.602).Conclusions: TRUS-PB UTI prophylaxis with FT and FQ has similar efficacy and safety. A randomized comparison of these two antibiotics is warranted.

Summary Objective. - To update French guidelines for the management of bladder cancer specifically non-muscle invasive (NMIBC) and muscle-invasive bladder cancers (MIBC). Methods. - A Medline search was achieved between 2018 and 2020, notably regarding diagnosis, options of treatment and follow-up of bladder cancer, to evaluate different references with levels of evidence. Results. - Diagnosis of NMIBC (Ta, T1, CIS) is based on a complete deep resection of the tumor. The use of fluorescence and a second-look indication are essential to improve initial diagnosis. Risks of both recurrence and progression can be estimated using the EORTC score. A stratification of patients into low, intermediate and high risk groups is pivotal for recommending adjuvant treatment: instillation of chemotherapy (immediate post-operative, standard schedule) or intravesical BCG (standard schedule and maintenance). Cystectomy is recommended in BCG-refractory patients. Extension evaluation of MIBC is based on contrast-enhanced pelvic-abdominal and thoracic CT-scan. Multiparametric MRI can be an alternative. Cystectomy associated with extended lymph nodes dissection is considered the gold standard for non-metastatic MIBC. It should be preceded by cisplatin-based neoadjuvant chemotherapy in eligible patients. An orthotopic bladder substitution should be proposed to both male and female patients with no contraindication and in cases of negative frozen urethral samples; otherwise transileal ureterostomy is recommended as urinary diversion. All patients should be included in an Early Recovery After Surgery (ERAS) protocol. For metastatic MIBC, first-line chemotherapy using platin is recommended (GC or MVAC), when performans status (PS 60 mL/min) allow it (only in 50% of cases). In second line treatment, immunotherapy with pembrolizumab demonstrated a significant improvement in overall survival. Conclusion. - These updated French guidelines will contribute to increase the level of urological care for the diagnosis and treatment of patients diagnosed with NMIBC and MIBC.

summary Introduction. –The purpose was to propose an update of the French guidelines from the national committee ccAFU on upper tract urothelial carcinomas (UTUC). Methods. – A systematic Medline search was performed between 2018 and 2020, as regards diagnosis, options of treatment and follow-up of UTUC, to evaluate different references with levels of evidence. Results. – The diagnosis of this rare pathology is based on CT-scan acquisition during excretion and ureteroscopy with histological biopsies. Radical nephroureterectomy (RNU) remains the gold standard for surgical treatment, nevertheless a conservative endoscopic approach can be proposed for low risk lesion: unifocal tumor, possible complete resection and low grade and absence of invasion on CT-scan. Close monitoring with endoscopic follow-up (flexible ureteroscopy) in compliant patients is therefore necessary. After RNU, bladder instillation of chemotherapy is recommended to reduce risk of bladder recurrence. A systemic chemotherapy is recommended after RNU in pT2–T4 N0–3 M0 disease. Conclusion. – These updated guidelines will contribute to increase the level of urological care for diagnosis and treatment for UTUC.

Introduction : la sarcopenie evaluee a partir de la mesure de l’indice de masse musculaire striee (SMI) a ete etudie comme facteur predictif de morbi-mortalite en chirurgie. L’objectif de cette etude etait d’evaluer si elle etait predictive de la morbi-mortalite chez les patients pris en charge par cystectomie ou par traitement tri modal (TTM), associant radiotherapie et chimiotherapie apres resection endoscopique de la tumeur, pour une TVIM localisee. Materiels et methodes : les patients consecutifs de 2 centres hospitalo-universitaires traites par cystectomie ou par TTM ont ete inclus. Le SMI etait calcule a partir de coupes axiales en L3 sur les scanners pre-therapeutiques. La sarcopenie a ete evaluee de deux facons : soit par le SMI sans ajustement de la masse musculaire, soit en utilisant la definition de Martin prenant en compte le sexe et l’IMC des patients, alors appelee « sarcopenie ajustee ». Le critere de jugement principal etait la survie globale (SG) en fonction de la sarcopenie. Les criteres secondaires etaient la SG, la survie sans progression (SSP) et la survie sans re-hospitalisation (SSR) pour la population totale et pour chaque groupe de traitement. Les analyses de survie ont ete realisees selon le modele de Cox. L’association entre sarcopenie et complications a ete recherchee par le test du Chi 2. Resultats : les caracteristiques des patients sarcopeniques et non sarcopeniques etaient comparables excepte pour 2 criteres : patients plus âges dans le groupe sarcopenique et proportion plus importante de chimiotherapie neo-adjuvante chez les patients non sarcopeniques. La sarcopenie ajustee n’etait significativement associee a aucun type de survie contrairement au SMI qui etait associe a la SG et a la SSR dans la population totale (p = 0.01 et p = 0.02) et a la SG dans le groupe de patients traites par cystectomie (p = 0.02). La sarcopenie n’etait associee ni a la proportion ni a la severite des complications. Conclusion : le SMI calcule avant la prise en charge des TVIM etait associe a la survie dans notre etude contrairement a la sarcopenie ajustee. Le choix d’un seuil de SMI faciliterait son utilisation par le praticien mais se heurte a la definition d’un seuil applicable a toutes les populations.

Tumor spheroids play an increasingly important role in cancer research. Their ability to recapitulate crucial features of tumor biology that are lost in the classically used 2D models along with their relative simplicity and handiness have made them the most studied 3D tumor model. Their application as a theranostic tool or as a means to study tumor-host interaction is now well-established in various cancers. However, their use in the field of Renal Cell Carcinoma (RCC) remains very limited. The aim of this work is to present methods to implement a basic RCC spheroid model. These methods cover the steps from RCC tumor dissociation to spheroid infiltration by immune cells. We present a protocol for RCC dissociation using Liberase TM and introduce a culture medium containing Epithelial Growth Factor and Hydrocortisone allowing for faster growth of RCC primary cells. We show that the liquid overlay technique allows for the formation of spheroids from cell lines and from primary cultures. We present a method using morphological criteria to select a homogeneous spheroid population based on a Fiji macro. We then show that spheroids can be infiltrated by PBMCs after activation with OKT3 or IL-15. Finally, we provide an example of application by implementing an immune spheroid killing assay allowing observing increased spheroid destruction after treatment with PD-1 inhibitors. Thus the straightforward methods presented here allow for efficient spheroid formation for a simple RCC 3D model that can be standardized and infused with immune cells to study immunotherapies.

International audience; Introduction. - Intravesical instillations of mitomycin C, epirubicin and BCG are considered as the standard treatment for most patients diagnosed with non-muscle invasive bladder cancer. These guidelines aim to optimize the adjuvant intravesical treatment in order to increase the efficacy and lower the morbidity associated with its administration.& nbsp;Methods. - We conducted a daily practice survey, an online search of available national regulation recommendations and of published guidelines. A bibliography search in French and English using Medline (R) and Embase (R) with the keywords ``BCG ``; ``mitomycin C ``; ``epirubicin ``; ``bladder ``; ``complication ``; ``toxicity ``; ``adverse reaction ``; ``prevention `` and ``treatment `` was performed November 2021.& nbsp;Results. - Patient information should be given by the attending physician before the first intravesical instillation. A medical exam to look for specific contraindications is also mandatory to select adequate candidates. Intravesical instillations should be delivered in health-care centers where urologic endoscopic procedures are routinely performed. Attending urologist or specialized nurse should check for negative pretreatment urine test. Intravesical instillation can only be delivered after bladder catheter has been inserted in the bladder without any injury of the lower urinary tract. The pharmaceutical agent should be kept in the bladder for two hours. Finally, voiding within the 6 hours following intravesical instillations should be done in the sitting position and the patient should drink at least 2 liters of water per day for 2 days.& nbsp;Conclusion. - The delivery of intravesical instillations of mitomycin C, epirubicin and BCG should follow a standardized procedure for better efficacy and lower morbidity. (C) 2022 Elsevier Masson SAS. All rights reserved.

Context: The European Association of Urology (EAU) has released an updated version of the guidelines on non-muscle-invasive bladder cancer (NMIBC). Objective: To present the 2021 EAU guidelines on NMIBC. Evidence acquisition: A broad and comprehensive scoping exercise covering all areas of the NMIBC guidelines since the 2020 version was performed. Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries. Previous guidelines were updated, and the level of evidence and grade of recommendation were assigned. Evidence synthesis: Tumours staged as Ta, T1 and carcinoma in situ (CIS) are grouped under the heading of NMIBC. Diagnosis depends on cystoscopy and histological evaluation of tissue obtained via transurethral resection of the bladder (TURB) for papillary tumours or via multiple bladder biopsies for CIS. For papillary lesions, a complete TURB is essential for the patient's prognosis and correct diagnosis. In cases for which the initial resection is incomplete, there is no muscle in the specimen, or a T1 tumour is detected, a second TURB should be performed within 2-6 wk. The risk of progression may be estimated for individual patients using the 2021 EAU scoring model. On the basis of their individual risk of progression, patients are stratified as having low, intermediate, high, or very high risk, which is pivotal to recommending adjuvant treatment. For patients with tumours presumed to be at low risk and for small papillary recurrences detected more than 1 yr after a previous TURB, one immediate chemotherapy instillation is recommended. Patients with an intermediate-risk tumour should receive 1 yr of full-dose intravesical bacillus Calmette-Guerin (BCG) immunotherapy or instillations of chemo therapy for a maximum of 1 yr. For patients with high-risk tumours, full-dose intravesical BCG for 1-3 yr is indicated. For patients at very high risk of tumour progression, immediate radical cystectomy should be considered. Cystectomy is also recommended for BCG-unresponsive tumours. The extended version of the guidelines is available on the EAU website at https://uroweb.org/guideline/non-muscle-invasive-bladder-cancer/. Conclusions: These abridged EAU guidelines present updated information on the diagnosis and treatment of NMIBC for incorporation into clinical practice. Patient summary: The European Association of Urology has released updated guidelines on the classification, risk factors, diagnosis, prognostic factors, and treatment of non- muscle-invasive bladder cancer. The recommendations are based on the literature up to 2020, with emphasis on the highest level of evidence. Classification of patients as having low, intermediate, or and high risk is essential in deciding on suitable treatment. Surgical removal of the bladder should be considered for tumours that do not respond to bacillus Calmette-Guerin (BCG) treatment and tumours with the highest risk of progression. (c) 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Background Literature lacks clear evidence regarding the optimal treatment for non–muscle-invasive micropapillary bladder cancer (MPBC) due to its rarity and the presence of only small sample size and single-centre studies. Objective To assess cancer-specific mortality (CSM) and overall mortality (OM) between immediate radical cystectomy (RC) and conservative management among T1 high-grade (HG) MPBC. Design, setting, and participants We retrospectively analysed a multicentre dataset including 119 T1 HG MPBC patients treated between 2005 and 2019 at 15 tertiary referral centres. The median follow-up time was 35 mo (interquartile range: 19–64). Intervention Patients underwent immediate RC versus conservative management with bacillus Calmette-Guerin. Outcomes measurements and statistical analysis Cumulative incidence functions and Kaplan-Meier methods were applied to estimate survival outcomes. Multivariable Cox analyses were performed to assess independent predictors of disease recurrence and disease progression after conservative management; covariates consisted of pure MPBC, concomitant lymphovascular invasion (LVI), and carcinoma in situ at initial diagnosis. Results and limitations Immediate RC and conservative management were performed in 27% and 73% of patients, respectively. CSM and OM did not differ significantly among patient treated with immediate RC versus conservative management (Pepe-Mori test p = 0.5 and log-rank test p = 0.9, respectively). Overall, 66.7% and 34.5% of patients experienced disease recurrence and disease progression after conservative management, respectively. At multivariable Cox analyses, concomitant LVI was an independent predictor of disease recurrence (p = 0.01) and progression (p = 0.03), while pure MPBC was independently associated with disease progression (p = 0.03). The absence of a centralised re-review and the retrospective design represent the main limitations of our study. Conclusions Conservative management could achieve satisfactory results among T1 HG MPBC patients with neither pure MPBC nor LVI at initial diagnosis. Patient summary Bacillus Calmette-Guerin seems to be an effective therapy for T1 micropapillary bladder cancer patients with neither pure micropapillary disease nor lymphovascular invasion at initial diagnosis.

Resume L’hematurie microscopique est un motif frequent de consultation en Urologie et concerne des populations de tous âges. Les benefices du bilan (identifier une pathologie urologique et en particulier un carcinome urothelial) doivent etre mis en perspective des risques potentiels (infection urinaire, irradiation). Tout venant, le risque de retrouver un cancer chez un patient adresse pour une hematurie microscopique est de l’ordre de 3 %. Cependant, plusieurs facteurs ont ete clairement identifies comme associes a la decouverte d’une neoplasie de l’appareil urinaire tels que l’âge, le sexe, le tabagisme ou les symptomes associes. Les recommandations europeennes et americaines sont en faveur d’une abstention d’examens invasifs ou irradiants chez les patients de moins de 40 ans. Apres 40 ans, il est possible de classer les patients en groupes de risque et d’adapter le bilan etiologique. Les patients de plus de 60 ans et/ou presentant des facteurs de risque doivent imperativement beneficier d’une cystoscopie, d’une cytologie urinaire et d’un uroscanner.

Intravesical instillations of BCG are recommended for the treatment of high-risk non-muscle-invasive bladder cancer. However, their prolonged use remains limited by the associated potentially serious adverse effects or complications. The purpose of this article was to provide updated recommendations for the diagnosis and management of adverse events (AEs) or complications of intravesical BCG instillations.Review of the literature in Medline (http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com) using the following MeSH keywords or a combination of these keywords: "bladder," "BCG," "complication," "toxicity," "adverse events," "prevention," and "treatment".AEs or complications of BCG included genitourinary and systemic symptoms. The most common complications (cystitis, moderate fever) should be treated symptomatically and may require adjustment to allow patients to have the most complete BCG treatment possible. Serious complications are rare but must be identified promptly because of the life-threatening nature of the disease. Their management is based on the combination of anti-tuberculosis treatments, anti-inflammatory drugs and the definitive discontinuation of BCG.The management of BCG AEs requires early identification, rational and effective treatment if necessary, and discussion of the continuation of treatment for each situation.

Intravesical instillations of mitomycin C, epirubicin and BCG are considered as the standard treatment for most patients diagnosed with non-muscle invasive bladder cancer. These guidelines aim to optimize the adjuvant intravesical treatment in order to increase the efficacy and lower the morbidity associated with its administration.We conducted a daily practice survey, an online search of available national regulation recommendations and of published guidelines. A bibliography search in French and English using Medline® and Embase® with the keywords "BCG"; "mitomycin C"; "epirubicin"; "bladder"; "complication"; "toxicity"; "adverse reaction"; "prevention" and "treatment" was performed November 2021.Patient information should be given by the attending physician before the first intravesical instillation. A medical exam to look for specific contraindications is also mandatory to select adequate candidates. Intravesical instillations should be delivered in health-care centers where urologic endoscopic procedures are routinely performed. Attending urologist or specialized nurse should check for negative pretreatment urine test. Intravesical instillation can only be delivered after bladder catheter has been inserted in the bladder without any injury of the lower urinary tract. The pharmaceutical agent should be kept in the bladder for two hours. Finally, voiding within the 6hours following intravesical instillations should be done in the sitting position and the patient should drink at least 2 liters of water per day for 2 days.The delivery of intravesical instillations of mitomycin C, epirubicin and BCG should follow a standardized procedure for better efficacy and lower morbidity.

Mitomycin C is the gold standard intravesical adjuvant therapy for intermediate-risk non-muscle-invasive bladder cancer (NMIBC). Tensions in the supply of mitomycin have emerged in France since late 2019. The ANSM in agreement with the AFU proposed to use epirubicin, already available in other European countries in this indication. The objective of our study was to report the initial French experience with the use of epirubicin in adjuvant treatment of NMIBC.We undertook a French multicenter retrospective descriptive study to collect, from the centers of the members of the CC-AFU bladder, the clinico-pathological data of the patients, the indications, the modalities of use (dose, indication, circuit in the pharmacy) and the tolerance data of epirubicin. The impact of the COVID-19 epidemic on treatment interruptions was also identified. Of the 20 centers contacted, 5 (25%) had implemented the epirubicin administration protocol developed by the CC-AFU bladder subcommittee. A total of 61 patients were treated with endovesical instillations of epirubicin between November 2019 and November 2020 for NMIBC at a single dose of 50mg.A total of 61 patients (mean age 67 years, 64-77 years) were treated with epirubicin, of which 45 (73.8%) were male. The patients had intermediate-risk NMIBC in 88.5%, the rest had high-risk disease. Induction therapy without or with maintenance was planned for 48 (78.7%) and 13 patients (21.3%), respectively. The preparation and administration of epirubicin was similar to that of mitomycin: central pharmacy preparation for same-day dispensing with immediate outpatient instillation. Unlike mitomycin, urinary alkalinization was not required. Of the 498 total instillations scheduled, 345 were performed (69.3%). The COVID-19 epidemic significantly impacted epirubicin delivery: one patient could not start treatment (1.6%), 8 patients (13.1%) had to discontinue it permanently; the rest of the patients underwent delayed instillations (18%). Other causes of discontinuation included infectious complications (9.8%). No major toxicities were reported.The implementation of an adjuvant epirubicin treatment protocol presented a good feasibility with low toxicity, without modifying the organization of the patients' care pathway. In the context of unpredictable mitomycin shortage, epirubicin represents a good therapeutic alternative in the endovesical adjuvant treatment of intermediate-risk NMIBC.3.

Resume La surveillance apres BCG-therapie est souvent difficile en raison des reactions inflammatoires vesicales induites par le traitement. En particulier l’identification du carcinome in situ est ardue. En moyenne, environ 20 % des lesions inflammatoires post BCG sont tumorales. La surveillance des patients porteurs de TVNIM a haut risque repose principalement sur la combinaison de cystoscopies regulieres et de cytologies urinaires. C’est la combinaison des deux examens qui offre la meilleure performance diagnostique, l’un ne devant pas se passer de l’autre. La decision de realiser des biopsies vesicales en cas de lesions inflammatoires doit etre guidee par les caracteristiques de la tumeur initiale et les donnees de la cytologie et de la cystoscopie. L’utilisation de la fluorescence est possible dans le contexte post BCG et permet d’augmenter la detection des recidives. La crainte des faux positifs oblige a respecter un delai minimum entre instillation et resection sous fluorescence.

Purpose: Conflicting evidence exists on the complication rates after cystectomy following previous radiation (pRTC) with only a few available series. We aim to assess the complication rate of pRTC for abdominal–pelvic malignancies. Methods: Patients treated with radical cystectomy following any previous history of RT and with available information on complications for a minimum of 1year were included. Univariable and multivariable logistic regression models were used to assess the relationship between the variable parameters and the risk of any complication. Results: 682 patients underwent pRTC after a previous RT (80.5% EBRT) for prostate, bladder (BC), gynecological or other cancers in 49.1%, 27.4%, 9.8% and 12.9%, respectively. Overall, 512 (75.1%) had at least one post-surgical complication, classified as Clavien ≥ 3 in 29.6% and Clavien V in 2.9%. At least one surgical complication occurred in 350 (51.3%), including bowel leakage in 6.2% and ureteric stricture in 9.4%. A medical complication was observed in 359 (52.6%) patients, with UTI/pyelonephritis being the most common (19%), followed by renal failure (12%). The majority of patients (86%) received an incontinent urinary diversion. In multivariable analysis adjusted for age, gender and type of RT, patients treated with RT for bladder cancer had a 1.7 times increased relative risk of experiencing any complication after RC compared to those with RT for prostate cancer (p = 0.023). The type of diversion (continent vs non-continent) did not influence the risk of complications. Conclusion: pRTC carries a high rate of major complications that dramatically exceeds the rates reported in RT-naïve RCs.

INTRODUCTION AND OBJECTIVE:At present no clear indication exists regarding the optimal treatment for non-muscle invasive micropapillary bladder cancer (NMI-MPBC). We compared cancer-specific surviv...