Learning curve for fusion magnetic resonance imaging targeted prostate biopsy and three-dimensional transrectal ultrasonography segmentation.

OBJECTIVE: To report the learning curve of multiple operators for fusion magnetic resonance imaging (MRI) targeted biopsy and to determine the number of cases needed to achieve proficiency. MATERIALS AND METHODS: All adult males who underwent fusion MRI targeted biopsy between February 2012 and July 2021 for clinically suspected prostate cancer (PCa) in a single centre were included. Fusion transrectal MRI targeted biopsy was performed under local anaesthesia using the Koelis platform. Learning curves for segmentation of transrectal ultrasonography (TRUS) images and the overall MRI targeted biopsy procedure were estimated with locally weighted scatterplot smoothing by computing each operator's timestamps for consecutive procedures. Non-risk-adjusted cumulative sum (CUSUM) methods were used to create learning curves for clinically significant (i.e., International Society of Urological Pathology grade ≥ 2) PCa detection. RESULTS: Overall, 1721 patients underwent MRI targeted biopsy in our centre during the study period. The median (interquartile range) times for TRUS segmentation and for the MRI targeted biopsy procedure were 4.5 (3.5, 6.0) min and 13.2 (10.6, 16.9) min, respectively. Among the 14 operators with experience of more than 50 cases, a plateau was reached after 40 cases for TRUS segmentation time and 50 cases for overall MRI targeted biopsy procedure time. CUSUM analysis showed that the learning curve for clinically significant PCa detection required 25 to 45 procedures to achieve clinical proficiency. Pain scores ranged between 0 and 1 for 84% of patients, and a plateau phase was reached after 20 to 100 cases. CONCLUSIONS: A minimum of 50 cases of MRI targeted biopsy are necessary to achieve clinical and technical proficiency and to reach reproducibility in terms of timing, clinically significant PCa detection, and pain.

A collaborative review of the microsatellite instability/deficient mismatch repair phenotype in patients with upper tract urothelial carcinoma.

OBJECTIVE: To perform a collaborative review of the literature exploring the microsatellite instability/deficient mismatch repair (MSI/dMMR) phenotype in patients with upper tract urothelial carcinoma (UTUC). METHOD: A collaborative review of the literature available on Medline was conducted by the Cancer Committee of the French Association of Urology to report studies describing the genetic mechanisms, investigation, prevalence and impact of the MSI/dMMR phenotype in UTUC patients. RESULTS: The predominant genetic mechanism leading to the MSI/dMMR phenotype in UTUC patients is related to the constitutional mutation of one allele of the MMR genes MLH1, MSH2, MSH6 and PMS2 within Lynch syndrome. Indications for its investigation currently remain limited to patients with a clinical suspicion for sporadic UTUC to refer only those with a positive testing for germline DNA sequencing to screen for this syndrome. With regard to technical aspects, despite the interest of MSIsensor, only PCR and immunohistochemistry are routinely used to somatically investigate the MSI and dMMR phenotypes, respectively. The prevalence of the MSI/dMMR phenotype in UTUC patients ranges from 1.7% to 57%, depending on the study population, investigation method and definition of a positive test. Younger age and a more balanced male to female ratio at initial diagnosis are the main specific clinical characteristics of UTUC patients with an MSI/dMMR phenotype. Despite the conflicting results available in the literature, these patients may have a better prognosis, potentially related to more favourable pathological features. Finally, they may also have lower sensitivity to chemotherapy but greater sensitivity to immunotherapy. CONCLUSION: Our collaborative review summarises the available data from published studies exploring the MSI/dMMR phenotype in UTUC patients, the majority of which are limited by a low level of evidence.

Role of Antimuscarinics Combined With Alpha-blockers in the Management of Urinary Storage Symptoms in Patients With Benign Prostatic Hyperplasia: An Updated Systematic Review and Meta-analysis.

PURPOSE: We evaluate the efficacy and safety of combining antimuscarinics with alpha-blockers to treat storage symptoms in men with benign prostatic hyperplasia. MATERIALS AND METHODS: Searches were carried out on PubMed, MEDLINE, EMBASE, and Cochrane databases to identify randomized, placebo-controlled trials published before February 15, 2022, assessing the efficacy or safety of antimuscarinics in men with benign prostatic hyperplasia treated with alpha-blockers. Further meta-analyses were performed using standardized mean difference and risk ratio. RESULTS: A total of 12 randomized trials were included in the systematic review. The meta-analysis showed no impact of antimuscarinics on the number of urgencies per day (SMD -0.23 [95%CI: -0.64; -0.17]; P = .21). However, the use of antimuscarinics was associated with a small reduction of micturition episodes per day (SMD -0.19 [95%CI: -0.37; -0.01]; P = .045). With regard to side effects, post-void residual increased slightly in patients treated with antimuscarinics (SMD 0.26 [95%CI: 0.15; 0.37]; P < .01). In addition, there was a higher risk of acute urinary retention (RR 3.26 [95%CI: 1.35; 7.86]; P = .02), dry mouth (RR 3.43 [95%CI: 1.86; 6.32]; P < .001), and constipation (RR 2.92 [95%CI: 1.48; 5.73]; P < .001) with the use of antimuscarinics. Finally, the risk of treatment interruption due to adverse events was higher for the patients treated with antimuscarinics (RR 1.74 [95%CI: 1.27; 2.38]; P < .01). CONCLUSIONS: The addition of antimuscarinics to alpha-blockers was not associated with a substantial reduction in urgencies and micturition episodes in benign prostatic hyperplasia patients with storage symptoms. In addition, the toxicity profile was not in favor of antimuscarinic use in these patients.

A prospective descriptive 1-year study in France of all BCG therapy dispensations for non-muscle-invasive bladder cancer.

OBJECTIVES: To describe the clinico-pathological characteristics of non-muscle-invasive bladder cancer (NMIBC) treated in metropolitan France over 1 year when bacille Calmette-Guérin (BCG) was subject to a national quota, and to document, in the context of recurrent shortages of intravesical BCG for NMIBC, the real-life indications for adjuvant treatment. MATERIALS AND METHODS: Between February 2021 and February 2022, the French National Agency for the Safety of Medicines (ANSM) asked the French Association of Urology 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 prioritize 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. RESULTS: During the 1-year quota, 25 878 requests for BCG were made for 19 024 patients, 60.5% of whom were aged ≥70 years. Requests for induction and maintenance treatment accounted for 12 704 (49.1%) and 13 174 prescriptions (50.9%), respectively. NMIBC treated with BCG maintenance therapy was more frequently high-risk NMIBC (91.7% vs 90.2%; P < 0.0001) than NMIBC 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. CONCLUSIONS: 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.

Prognostic value of programmed death ligand-1 and programmed death-1 expression in patients with upper tract urothelial carcinoma.

OBJECTIVE: To evaluate the prognostic value of programmed death ligand-1 (PD-L1) and programmed death-1 (PD-1) expression in patients with upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: A retrospective multicentre study was conducted in 283 patients with UTUC treated with radical nephroureterectomy (RNU) between 2000 and 2015 at 10 French hospitals. Immunohistochemistry analyses were performed using 2 mm-core tissue microarrays with NAT105® and 28.8® antibodies at a 5% cut-off for positivity on tumour cells and tumour-infiltrating lymphocytes to evaluate PD-L1 and PD-1 expression, respectively. Multivariable Cox regression models were used to determine the independent predictors of recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS). RESULTS: Overall, 63 (22.3%) and 220 (77.7%) patients with UTUC had PD-L1-positive and -negative disease, respectively, while 91 (32.2%) and 192 (67.8%) had PD-1-positive and -negative disease, respectively. Patients who expressed PD-L1 or PD-1 were more likely to have pathological tumour stage ≥pT2 (68.3% vs 49.5%, P = 0.009; and 69.2% vs 46.4%, P < 0.001, respectively) and high-grade (90.5% vs 70.0%, P = 0.001; and 91.2% vs 66.7%, P < 0.001, respectively) disease with lymphovascular invasion (52.4% vs 17.3%, P < 0.001; and 39.6% vs 18.2%, P < 0.001, respectively) as compared to those who did not. In multivariable Cox regression analysis adjusting for each other, PD-L1 and PD-1 expression were significantly associated with decreased RFS (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.09-3.08, P = 0.023; and HR 1.59, 95% CI 1.01-2.54, P = 0.049; respectively), CSS (HR 2.73, 95% CI 1.48-5.04, P = 0.001; and HR 1.96, 95% CI 1.12-3.45, P = 0.019; respectively) and OS (HR 2.08, 95% CI 1.23-3.53, P = 0.006; and HR 1.71, 95% CI 1.05-2.78, P = 0.031; respectively). In addition, multivariable Cox regression analyses evaluating the four-tier combination of PD-L1 and PD-1 expression showed that only PD-L1/PD-1-positive patients (n = 38 [13.4%]) had significantly decreased RFS (HR 3.07, 95% CI 1.70-5.52; P < 0.001), CSS (HR 5.23, 95% CI 2.62-10.43; P < 0.001) and OS (HR 3.82, 95% CI 2.13-6.85; P < 0.001) as compared to those with PD-L1/PD-1-negative disease (n = 167 [59.0%]). CONCLUSIONS: We observed that PD-L1 and PD-1 expression were both associated with adverse pathological features that translated into an independent and cumulative adverse prognostic value in UTUC patients treated with RNU.

Perioperative, renal function and oncological outcomes of robot-assisted radical nephroureterectomy for patients with upper tract urothelial carcinoma.

PURPOSE: To report perioperative, renal function and oncological outcomes of robot-assisted radical nephroureterectomy (RNU) for patients with upper tract urothelial carcinoma (UTUC). METHODS: This was a retrospective single-arm monocentric study including all consecutive UTUC patients treated with robot-assisted RNU at our institution between 2014 and 2022. Descriptive statistics with median and interquartile range (IQR) for continuous variables and numbers with frequencies for categorical variables were used to report perioperative and renal function outcomes while Kaplan-Meier curves were computed to present extravesical and intravesical recurrence-free survival(RFS) as well as cancer-specific (CSS) and overall survival (OS) with the corresponding 95% confidence intervals(CIs). RESULTS: Overall, 70 patients with a median age of 69.6 [63.3-74.9] years were included in our study. With regards to perioperative outcomes, the median operative time was 157 [130-182] min with a median blood loss of 200 [100-300] cc. Intraoperative complications occurred in 4 (5.7%) patients but no conversion to open or laparoscopic surgery was required. Postoperative complications occurred in 9 (12.9%) patients, including 5 (7.1%) with grade ≥ 3 complications according to the Clavien-Dindo classification. The median length of stay was 4 [3-6] days. With regards to renal function outcomes, the median postoperative loss in estimated glomerular filtration rate at discharge was 16 [10.25-26] mL/min/1.73 m2. With regards to oncological outcomes, the 3-year extravesical and intravesical RFS, CSS and OS rates were 73.6 [62.8-86.2]%, 68.1 [54.6-85]%, 82.5 [72-94.4]% and 75.3 [63.4-89.5]%, respectively. CONCLUSION: We report favorable perioperative and oncological outcomes with expected decrease in renal function after robot-assisted RNU for patients with UTUC.

Design and rationale of a single-arm phase II study of neoadjuvant Durvalumab and Gemcitabine associated with Cisplatin or Carboplatin for upper urinary tract urothelial cancer: the iNDUCT trial (NCT04617756).

BACKGROUND: Upper urinary tract urothelial carcinoma (UTUC) is often locally advanced at initial diagnosis and is associated with high recurrence and mortality rates after radical nephroureterectomy (RNU). Adjuvant platinum-based chemotherapy has shown a recurrence-free survival benefit in a randomised phase III trial, while neoadjuvant treatment seems promising in retrospective series. On the contrary, little is known about the role of perioperative immunotherapy and its combination with chemotherapy for UTUC patients, although initial positive results have been published for muscle-invasive bladder cancer. STUDY DESIGN AND ENDPOINTS: Against this backdrop, we are running a multi-centre single-arm phase 2 trial of neoadjuvant Durvalumab, a monoclonal antibody targeting programmed cell death ligand 1, combined with Gemcitabine and Cisplatin or Carboplatin for high-risk UTUC patients. The primary outcome is pathological complete response rate at RNU. Secondary endpoints include the partial pathological response rate, safety, as well as disease-free and overall survival. A biomarker analysis is also planned. PATIENTS AND INTERVENTIONS: Included patients must have a good performance status and harbour a non-metastatic UTUC, considered at high risk of progression, defined as either biopsy-proven high-grade disease or invasive features at imaging with or, more recently, without high-grade cytology at the multidisciplinary team discretion, as specified in the latest amendment. Enrolled patients receive 3 cycles of neoadjuvant immuno-chemotherapy before RNU, and the standard of care thereafter. The trial is registered as NCT04617756 and is supervised by an independent data monitoring committee.

The role of perioperative chemotherapy for upper tract urothelial carcinoma patients treated with radical nephroureterectomy.

PURPOSE: To summarize evidence regarding the use of neoadjuvant (NAC) and adjuvant chemotherapy (AC) among patients treated with radical nephroureterectomy (RNU). METHODS: A comprehensive literature search of PubMed (MEDLINE), EMBASE and the Cochrane library was performed to identify any original or review article on the role of perioperative chemotherapy for UTUC patients treated with RNU. RESULTS: With regards to NAC, retrospective studies consistently suggested that it may be associated with better pathological downstaging (pDS) ranging from 10.8 to 80% and complete response (pCR) ranging from 4.3 to 15%, while decreasing the risk of recurrence and death as compared to RNU alone. Even higher pDS ranging from 58 to 75% and pCR ranging from 14 to 38% were observed in single-arm phase II trials. With regards to AC, retrospective studies provided conflicting results although the largest report from the National Cancer Database suggested an overall survival benefit in pT3-T4 and/or pN + patients. In addition, a phase III randomized controlled trial showed that the use of AC was associated with a disease-free survival benefit (HR = 0.45; 95% CI = [0.30-0.68]; p = 0.0001) in pT2-T4 and/or pN + patients with acceptable toxicity profile. This benefit was consistent in all subgroups analyzed. CONCLUSIONS: Perioperative chemotherapy improves oncological outcomes associated with RNU. Given the impact of RNU on renal function, the rational is stronger for the use of NAC which impacts final pathology and potentially prolongs survival. However, the level of evidence is stronger for the use of AC that has been proven to decrease the risk of recurrence after RNU with a potential survival benefit.

Robotic versus open simple prostatectomy for benign prostatic hyperplasia in large glands: single-centre study.

PURPOSE: Robot-assisted simple prostatectomy (RASP) for benign prostatic hyperplasia (BPH) is a recently described surgical approach, but comparison with open simple prostatectomy (OSP) lack in the literature. We compared perioperative outcomes of OSP versus RASP. METHODS: Patients who underwent simple prostatectomy between 2017 and 2020 were included in this retrospective study. OSP was performed by the transvesical technique and RASP was performed with a DaVinci Xi robot, using the transvesical extraperitoneal approach. Perioperative and postoperative data were compared and complications risk factors for complications were identified. RESULTS: and limitations. Overall, 103 patients were included (median age 72 years [IQR = 67-76]). Forty-seven underwent RASP and 56 OSP. The median volume of the prostate gland was 130 mL [IQR = 100-180] in the RASP group and 126 mL [IQR = 100-160] in the OSP group. RASP was associated with a significant reduction in blood loss (median 200 vs. 400 mL; p < 0.001), shorter hospital stay (5 vs. 10 days; p < 0.001) and median catheterisation time (4 vs. 9 days; p < 0.001). In the RASP group, there were fewer grade ≥ 2 complications (2 (4.3%) vs. 13 (23.2%); p = 0.005) and less need for transfusions (0 vs. 6 (11%), p = 0.005). Preoperative prostate volume was a risk factor for complications (OR = 1.2 [95% CI 1.1-1.5]; p = 0.01) while robot-assisted surgery was a protective factor (OR 0.3 [95% CI 0.05-0.9]; p = 0.05). Functional outcomes between the two groups were identical at 12 months follow up. CONCLUSION: RASP is a safe and effective procedure. When compared with OSP, RASP was associated with decreased morbidity as well as reduced hospital stay and catheterisation time. Functional outcomes were comparable to the open approach.

Robotic versus open cystectomy with ileal conduit for the management of neurogenic bladder: a comparative study.

PURPOSE: Cystectomy associated with non-continent ileal diversion is a common surgery in patients with neurogenic bladder. Few data are available, especially for the robotic approach. Our purpose was to compare open cystectomy (OC) and robot-assisted radical cystectomy (RARC) with ileal conduit, regarding peri- and post-operative outcomes. METHODS: We included each patient who underwent cystectomy and ileal conduit for neurogenic bladder in a referral-center between January 2017 and November 2021. Data were retrospectively analyzed. Median follow-up was 16.6 months [IQR: 5; 41]. All patients had neurogenic bladder with failure of conservative treatment and/or impacted Quality of Life (QoL). Open cystectomy with non-continent ileal diversion and robot-assisted cystectomy with intra-corporeal non-continent ileal diversion were compared. Primary endpoint was postoperative complications. Secondary endpoints were length of hospital stay (LOS), surgery duration, blood loss and ureteral anastomosis stricture. RESULTS: A total of 123 patients were included, n = 85 (69.1%) undergoing OC and n = 38 (30.9%) RARC. Significant differences were observed for: operative time (OC 266.9 ± 64 vs. RARC 205.8 ± 55.5 min, p < 0.001), blood loss (OC 737.7 ± 515.8 vs. RARC 245.8 ± 169.6 ml, p < 0.001), delay until feeding resumption (OC 7.1 ± 4.7 vs. RARC 5.5 ± 2.9 days, p = 0.05) and mean LOS (OC 21.6 ± 13.9 vs. RARC 16.2 ± 7.6 days, p = 0.03). In RARC group, there were 10.5% complications Clavien-Dindo > 2 whereas 23.8% complications underwent in the OC group (p = 0.1). CONCLUSION: RARC is a safe approach for management of neurological bladder showing significantly better perioperative outcomes.

Urodynamic assessment and quality of life outcomes of robot-assisted totally intracorporeal radical cystectomy and orthotopic neobladder for bladder cancer: a preliminary study.

PURPOSE: Few data exist regarding the functional outcomes of robot-assisted radical cystectomy (RARC) with intracorporeal orthotopic neobladder. The aim of this study was to evaluate the urodynamic and functional outcomes in patients undergoing RARC and totally intracorporeal orthotopic neobladder for bladder cancer. METHODS: In this monocentric, observational study carried out between 2016 and 2020, consecutive patients undergoing RARC and intracorporeal orthotopic neobladder in the Department of Urology, Pitié-Salpêtrière Hospital, were included. Reconstruction was totally intracorporeal Y-shaped neobladder. Main outcomes were urodynamic findings 6 months post-surgery, continence and quality of life (QoL). Continence was defined by no pad or one safety pad. International Consultation on Incontinence Questionnaire (ICIQ), International Index of Erectile Function questionnaire (IIEF-5) and Bladder Cancer Index (BCI) scores were recorded. RESULTS: Fourteen male patients were included (median age: 64 years [IQR 54-67]. Median maximal neobladder cystometric capacity was 495 ml [IQR 410-606] and median compliance was 35.5 ml/cm H2O [IQR 28-62]. All patients had post-void residual volume < 30 ml, except for three (22%) who required clean intermittent-self catheterisation. Daytime continence was achieved in 10 patients (71%) and night-time continence in two (14.3%). Median ICIQ score was 7 [IQR 5-11]. Postoperative erectile function was present in 7% of patients (mean IIEF-5 = 5 [IQR 2-7]). Thirteen patients (93%) were satisfied with their choice of neobladder. CONCLUSION: RARC with totally intracorporeal orthotopic neobladder for bladder cancer provides satisfactory urodynamic results and good QoL. These findings should be confirmed long-term.

Standardizing immunohistochemistry methodology for evaluation of PD-1 and PDL-1 expression in upper tract urothelial carcinoma.

INTRODUCTION: Controversy regarding the prognostic and/or predictive role of PD-1 and PD-L1 expression for upper tract urothelial carcinoma (UTUC) could partly be explained by inconsistencies in the immunohistochemistry (IHC) methodology. Objective is to standardize the methodology for routine evaluation of PD-1 and PD-L1 expression in UTUC patients. MATERIALS AND METHODS: Twenty-two cases treated with radical nephroureterectomy between 1996 and 2015 at 11 French hospitals were randomly selected to compare different methodologies for evaluation of PD-1 and PD-L1 expression. IHC was carried out on whole tissue sections and 0.6 mm- or 2 mm-core tissue micro-arrays (TMAs) using PD-1 NAT105 and PD-L1 28.8 or E1L3N on both tumor cells and tumor-infiltrating immune cells (TILs). Results obtained with whole tissue sections (WTS) were compared to those obtained with 0.6 mm- and 2 mm-core TMAs. Concordance was evaluated using Kappa coefficient. RESULTS: For evaluation of PD-1 and PD-L1 expression, the best concordance with WTS was observed using the PD-1 NAT105 and PD-L1 28.8 antibody on 2 mm-core TMAs, with 5% cut off for positivity on TILs and tumor cells, respectively (Kappa = 0.8). CONCLUSIONS: The most accurate methodology for routine evaluation of PD-1 and PD-L1 expression in UTUC may be based on 2 mm-core TMAs using NAT105 and 28.8 antibodies with a 5% cut off for positivity on TILs and tumor cells, respectively.

Current status and future directions of the use of novel immunotherapeutic agents in bladder cancer.

PURPOSE OF REVIEW: To report the available information on the current status and future direction of the use of checkpoint inhibitors as novel immunotherapeutic agents in bladder cancer. RECENT FINDINGS: In the past 3 years, five immunotherapies targeting programmed cell death 1 (Pembrolizumab and Durvalumab) or programmed cell death-ligand 1 (PD-L1) (Atezolizumab, nivolumab and Avelumab) pathways have been approved in second-line setting for patients who progressed during or after cisplatin-based chemotherapy. According to the most recent update, these patients should be PD-L1-positive to be eligible for immunotherapy. The use of novel checkpoint inhibitors was also very promising in other settings: Metastatic urothelial carcinoma without prior systemic treatment (IMvigor-130), as neoadjuvant treatment before radical cystectomy in patients with muscle invasive disease (PURE-01), and in Bacillus Calmette-Guérin (BCG) refractory nonmuscle invasive bladder cancer (KEYNOTE 057). SUMMARY: Ongoing trials on the role of checkpoint inhibitors in bladder cancer may change our approach to different stages of bladder cancer. For metastatic urothelial carcinoma, the role of combined immune and chemotherapy may improve survival. For localized bladder cancer, immunotherapy as neoadjuvant therapy may be associated with less toxicity and better tolerability. Finally, in the setting of a BCG-refractory or BCG-naïve nonmuscle invasive disease checkpoint inhibitors may reduce/delay the risk of progression and subsequent cystectomy.

Bladder mapping of tumour recurrence after radical nephroureterectomy for upper tract urothelial carcinoma and its influence on oncological outcomes.

OBJECTIVES: To assess the location of intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), to determine the main predictive factors for IVR in the bladder-cuff area (BCA), and to assess the effect of BCA recurrence (BCAR) on prognosis. PATIENTS AND METHODS: This was a multicentre, retrospective study using the French collaborative database on UTUC, which includes data for all patients treated in 24 referral uro-oncology centres across the country. All patients who underwent RNU with bladder-cuff excision and who developed IVR between 1995 and 2010 were selected. Patients were divided into two groups: Group A: BCAR; and Group B: recurrence elsewhere in the bladder. The Kaplan-Meier method was used to estimate the probability of BCAR-free survival. Groups were compared using the log-rank test. Independent risk factors for BCAR were identified using a Cox proportional hazard regression model, with univariate and multivariate analyses. RESULTS: Overall, 163 patients were included in the final analysis: Group A, 87 patients (53.4%) and Group B, 76 (46.6%). The clinicopathological characteristics were similar in the groups. The median (interquartile range [IQR]) follow-up was 36 (31.7-40.39) months. The median (IQR) time to IVR was 10.0 (8.6-13.39) months [Group A: 11.0 (8.8-13.2)  months vs Group B: 10.0 (8.5-11.5) months; P = 0.35]. The probability of BCAR at 1, 2, and 3 years was 45.5% (95% confidence interval [CI] 40.1-50.9), 17.9% (95% CI 13.7-22.1), and 10.8% (95% CI 7.4-14.2) respectively, whereas the probability of recurrence elsewhere in the bladder was 42.1% (95% CI 36.4-47.8), 14.7% (95% CI 10.6-18.8), and 4.4% (95% CI 1.9-6.9), respectively (P = 0.35). Pathological tumour stage (≥pT3) was significantly related to the risk of BCAR (P = 0.03). CONCLUSION: There were more BCARs after RNU in advanced UTUC. However, no preferred site for recurrence was detected.

Incidence and survival outcomes in patients with upper urinary tract urothelial carcinoma diagnosed with variant histology and treated with nephroureterectomy.

OBJECTIVE: To evaluate the incidence and survival outcomes of histological variants of upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). MATERIALS AND METHODS: We retrospectively analysed data from 1610 patients treated with RNU for clinically non-metastatic UTUC between 1990 and 2016 in several centres participating in the UTUC Collaboration. Histological variants were classified as micropapillary, squamous, sarcomatoid and other, including other rare variants (<10 cases for each). Multivariable competing risk analyses were conducted to assess the effect of variant histology on overall recurrence and cancer-specific mortality (CSM). RESULTS: Overall, 1460 patients (91%) had pure urothelial carcinoma (PUC), whereas 150 (9%) were diagnosed with a variant histology, including 89 (5.0%), 41 (2.0%), 10 (1.0%) and 10 (1.0%) cases of micropapillary, squamous, sarcomatoid and other tumours, respectively. Variant histology was associated with the presence of adverse pathological features compared with PUC, including non-organ-confined disease (59% vs 38%; P < 0.001), lymph node invasion (28% vs 24%; P = 0.02), high-grade disease (88% vs 71%; P < 0.001), tumour necrosis (28% vs 16%; P = 0.001) and positive surgical margins (15% vs 8%; P = 0.01). In competing risk analysis, micropapillary variant was the only factor associated with worse recurrence (sub-hazard ratio [SHR] 2.27, 95% confidence interval [CI] 1.25-4.79; P = 0.02) whereas sarcomatoid variant was associated with worse CSM (SHR 16.8, 95% CI 6.86-41.17; P < 0.001). CONCLUSION: We found that one out of 10 patients with UTUC treated with RNU had variant histology. Only micropapillary and sarcomatoid variants were associated with poorer oncological outcomes after adjusting for available confounding factors.

Robotic radical nephroureterectomy and segmental ureterectomy for upper tract urothelial carcinoma: a multi-institutional experience.

PURPOSE: To report a multi-institutional experience on robotic radical nephroureterectomy (RNU) and segmental ureterectomy (SU) for upper tract urothelial carcinoma (UTUC). METHODS: Data were prospectively collected from patients with non-metastatic UTUC undergoing robotic SU or RNU at three referral centers between 2015 and 2018. Transperitoneal, single-docking robotic RNU followed established principles. Bladder cuff excision (BCE) was performed with robotic or open approach. Techniques for SU included: ureteral resection and primary uretero-ureterostomy; partial pyelectomy and modified pyeloplasty; ureteral resection with BCE and direct- or psoas hitch-ureteroneocystostomy. We retrospectively evaluated the technical feasibility, and peri-operative and oncologic outcomes after robotic RNU/SU. RESULTS: 81 patients were included. No case required conversion to open surgery. Early major (Clavien-Dindo grade > 2) complications were reported in six (7.4%) patients (two after SU, four after RNU). Three patients experienced late major complications (one after SU, two after RNU). Median ΔeGFR at 3 months was - 1 ml/min/1.73 m2 after SU and - 15 ml/min/1.73 m2 after RNU. Positive surgical margins were recorded in five patients (one after SU, four after RNU). Median follow-up was 21 months and 22 months in the SU and RNU groups, respectively. Three (20%) patients had ipsilateral upper tract recurrence after SU, while five (7.5%) developed metastases after RNU. No case of port-site metastases or peritoneal carcinomatosis was reported. At last follow-up, 67 (82.7%) patients were alive without evidence of disease. CONCLUSION: Robotic SU and RNU are technically feasible and achieved promising peri-operative and oncologic outcomes in selected patients with non-metastatic UTUC.

Outcomes after salvage radical prostatectomy and first-line radiation therapy or HIFU for recurrent localized prostate cancer: results from a multicenter study.

INTRODUCTION: Despite no consensus on the optimal management of recurrent prostate cancer after primary radiation or HIFU therapy, salvage prostatectomy (sRP) is reserved for only 3% of patients because of technical challenges and frequent post-operative complications. We assessed outcomes after sRP in a series of patients with localized PCa and that had received radiation therapy or HIFU as a first-line treatment. MATERIALS AND METHODS: Data from nine French referral centers on patients treated with sRP between 2005 and 2017 were collected. Pre- and post-operative data, including oncological and functional outcomes after first treatment and sRP, were analyzed to determine the predictors for biochemical recurrence (BCR) and cancer-specific survival (CSS) after sRP. RESULTS: First-line treatments were external beam-radiation therapy (EBRT) for 30 (55%), brachytherapy (BT) for 10 (18%), and high-intensity focused ultrasound (HIFU) for 15 (27%). Median (IQR) PSA at diagnosis was 6.4 (4.9-9.5) ng/mL, median PSA at nadir was 1.9 (0.7-3.0) ng/mL, and median (IQR) to first BCR was 13 (6-20) months. Of the 55 patients, 44 (80%) received robot-assisted salvage radical prostatectomy and 11 (20%) received salvage retropubic radical prostatectomy. Restoration of continence was achieved in 90% of preoperatively continent patients; 24% that had received nerve-sparing (NS) procedures were potent after surgery. Prolonged catheterization due to anastomotic leakage was the most common complication. Age, preoperative clinical stage, NS procedure, and a pathological Gleason score were predictors for BCR. CONCLUSIONS: sRP was safe, feasible, and effective using either an open or robot-assisted approach, in experienced hands. Age, preoperative clinical stage, NS procedure, and pathological GS were linked with BCR after sRP.

Functional outcomes of synthetic tape and mesh revision surgeries: a monocentric experience.

INTRODUCTION AND HYPOTHESIS: Synthetic tapes and meshes used for the treatment of stress urinary incontinence (SUI) and pelvic organ prolapse (POP) can lead to complications that require additional surgical procedures. The objective of this study was to report the functional outcomes following tape/mesh removal procedures. METHODS: This retrospective study included all consecutive women who underwent a tape/mesh surgical revision in a single tertiary referral center from January 2008 to September 2016. Descriptive statistics were performed to assess outcomes. RESULTS: Overall 140 women, with a mean age of 60.5 (range 35-91) years, had a tape/mesh surgical revision. Patients underwent the following surgeries: tape removal (n = 95/140, 67.9%), tape division (n = 23/140, 16.4%), mesh removal (n = 18/140, 12.9%) and concomitant tape and mesh removal (n = 4/140, 2.9%). Tape removals were mainly performed for voiding symptoms (n = 34/95, 35.8%) and vaginal erosion/extrusion (n = 16/95, 16.8%). Most mesh removals were performed for vaginal erosion/extrusion (n = 9/18, 50.0%). Mean interval between tape/mesh insertion and its surgical revision was 52.1 months (range 5.0 days-16.0 years). Mean follow-up time was 20.4 months (range 6.0 days-7.8 years). Voiding and storage symptoms resolved completely in 37/59 (62.7%) patients and in 14/37 (37.8%) patients, respectively; 42/81 (51.9%) patients with postoperative SUI recurrence or persistence underwent an additional surgical procedure. Among the 18 patients who had a mesh removal, only 1 (5.6%) had POP recurrence. CONCLUSION: Although most symptoms resolved after tape and mesh surgical revisions, patients must be informed that symptoms may persist. Recurrent or persistent SUI or POP may require a subsequent surgical procedure.

Peri-operative allogeneic blood transfusion does not adversely affect oncological outcomes after radical cystectomy for urinary bladder cancer: a propensity score-weighted European multicentre study.

OBJECTIVES: To evaluate the effect of peri-operative blood transfusion (PBT) on recurrence-free survival, overall survival, cancer-specific mortality and other-cause mortality in patients undergoing radical cystectomy (RC), using a contemporary European multicentre cohort. PATIENTS AND METHODS: The Prospective Multicentre Radical Cystectomy Series (PROMETRICS) includes data on 679 patients who underwent RC at 18 European tertiary care centres in 2011. The association between PBT and oncological survival outcomes was assessed using Kaplan-Meier, Cox regression and competing-risks analyses. Imbalances in clinicopathological features between patients receiving PBT vs those not receiving PBT were mitigated using conventional multivariable adjusting as well as inverse probability of treatment weighting (IPTW). RESULTS: Overall, 611 patients had complete information on PBT, and 315 (51.6%) received PBT. The two groups (PBT vs no PBT) differed significantly with respect to most clinicopathological features, including peri-operative blood loss: median (interquartile range [IQR]) 1000 (600-1500) mL vs 500 (400-800) mL (P < 0.001). Independent predictors of receipt of PBT in multivariable logistic regression analysis were female gender (odds ratio [OR] 5.05, 95% confidence interval [CI] 2.62-9.71; P < 0.001), body mass index (OR 0.91, 95% CI 0.87-0.95; P < 0.001), type of urinary diversion (OR 0.38, 95% CI 0.18-0.82; P = 0.013), blood loss (OR 1.32, 95% CI 1.23-1.40; P < 0.001), neoadjuvant chemotherapy (OR 2.62, 95% CI 1.37-5.00; P = 0.004), and ≥pT3 tumours (OR 1.59, 95% CI 1.02-2.48; P = 0.041). In 531 patients with complete data on survival outcomes, unweighted and unadjusted survival analyses showed worse overall survival, cancer-specific mortality and other-cause mortality rates for patients receiving PBT(P < 0.001, P = 0.017 and P = 0.001, respectively). After IPTW adjustment, those differences no longer held true. PBT was not associated with recurrence-free survival (hazard ratio [HR] 0.92, 95% CI 0.53-1.58; P = 0.8), overall survival (HR 1.06, 95% CI 0.55-2.05; P = 0.9), cancer-specific mortality (sub-HR 1.09, 95% CI 0.62-1.92; P = 0.8) and other-cause mortality (sub-HR 1.00, 95% CI 0.26-3.85; P > 0.9) in IPTW-adjusted Cox regression and competing-risks analyses. The same held true in conventional multivariable Cox and competing-risks analyses, where PBT could not be confirmed as a predictor of any given endpoint (all P values >0.05). CONCLUSION: The present results did not show an adverse effect of PBT on oncological outcomes after adjusting for baseline differences in patient characteristics.