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.

Is "Kidney Stone Calculator" efficient in predicting ureteroscopic lithotripsy duration? A holmium:YAG and thulium fiber lasers comparative analysis.

PURPOSE: This study aimed to evaluate the ability of Kidney Stone Calculator (KSC), a flexible ureteroscopy surgical planning software, to predict the lithotripsy duration with both holmium:YAG (Ho:YAG) and thulium fiber laser (TFL). METHODS: A multicenter prospective study was conducted from January 2020 to April 2023. Patients with kidney or ureteral stones confirmed at non-contrast computed tomography and treated by flexible ureteroscopy with laser lithotripsy were enrolled. "Kidney Stone Calculator" provided stone volume and subsequent lithotripsy duration estimation using three-dimensional segmentation of the stone on computed tomography and the graphical user interface for laser settings. The primary endpoint was the quantitative and qualitative comparison between estimated and effective lithotripsy durations. Secondary endpoints included subgroup analysis (Ho:YAG-TFL) of differences between estimated and effective lithotripsy durations and intraoperative outcomes. Multivariate analysis assessed the association between pre- and intraoperative variables and these differences according to laser source. RESULTS: 89 patients were included in this study, 43 and 46 in Ho:YAG and TFL groups, respectively. No significant difference was found between estimated and effective lithotripsy durations (27.37 vs 28.36 min, p = 0.43) with a significant correlation (r = + 0.89, p < 0.001). Among groups, this difference did not differ (p = 0.68 and 0.07, respectively), with a higher correlation between estimated and effective lithotripsy durations for TFL compared to Ho:YAG (r = + 0.95, p < 0.001 vs r = + 0.81, p < 0.001, respectively). At multivariate analysis, the difference was correlated with preoperative (volume > 2000 mm3 (Ho:YAG), 500-750 mm3 SV and calyceal diverticulum (TFL)), operative (fragmentation setting (p > 0.001), and basket utilization (p = 0.05) (Ho:YAG)) variables. CONCLUSION: KSC is a reliable tool for predicting the lithotripsy duration estimation during flexible ureteroscopy for both Ho:YAG and TFL. However, some variables not including laser source may lead to underestimating this estimation.

Predicting individual outcomes after radical cystectomy in urothelial variants with Cancer of the Bladder Risk Assessment (COBRA) score.

OBJECTIVE: To validate the Cancer of the Bladder Risk Assessment (COBRA) score in patients with urothelial variants. METHODS: Epidemiological, clinical, radiological, and anatomopathological data were collected from patients with urothelial carcinoma who underwent radical cystectomy at the Institute of Cancer of São Paulo between May 2008 and December 2022. Patients with the presence of at least 10% of any urothelial variants in the radical cystectomy specimens' anatomopathological exam were included in the study. The COBRA score and derivatives were applied and correlated with oncological outcomes. RESULTS: A total of 680 patients [482 men (70.9%) and 198 women (29.1%)]; 66 years (IQR 59-73) underwent radical cystectomy for bladder tumor, and of these patients, a total of 167 patients presented any type of urothelial variant. The median follow-up time was 28.77 months (IQR 12-85). The three most prevalent UV were squamous differentiation (50.8%), glandular differentiation (31.3%), and micropapillary differentiation (11.3%). The subtypes with the worst prognosis were sarcomatoid with a median survival of 8 months (HR 1.161; 95% CI 0.555-2.432) and plasmacytoid with 14 months (HR 1.466; 95% CI 0.528-4.070). The COBRA score for patients with micropapillary variants demonstrated good predictive accuracy for OS (log-rank P = 0.009; 95% IC 6.78-29.21) and CSS (log-rank P = 0.002; 95% IC 13.06-26.93). CONCLUSIONS: In our study, the COBRA score proved an effective risk stratification tool for urothelial histological variants, especially for the micropapillary urothelial variant. It may be helpful in the prognosis evaluation of UV patients after radical cystectomy.

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.

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.

Urinary biomarkers for bladder cancer diagnosis and NMIBC follow-up: a systematic review.

BACKGROUND: Bladder cancer detection and follow-up is based on cystoscopy and/or cytology, but it remains imperfect and invasive. Current research focuses on diagnostic biomarkers that could improve bladder cancer detection and follow-up by discriminating patients at risk of aggressive cancer who need confirmatory TURBT (Transurethral Resection of Bladder Tumour) from patients at no risk of aggressive cancer who could be spared from useless explorations. OBJECTIVE: To perform a systematic review of data on the clinical validity and clinical utility of eleven urinary biomarkers (VisioCyt®, Xpert®Bladder, BTA stat®, BTA TRAK™, NMP22 BC®, NMP22® BladderChek® Test, ImmunoCyt™/uCyt1+™, UroVysion Bladder Cancer Kit®, Cxbladder, ADXBLADDER, Urodiag®) for bladder cancer diagnosis and for non-muscle invasive bladder cancer (NMIBC) follow-up. METHODS: All available studies on the 11 biomarkers published between May 2010 and March 2021 and present in MEDLINE® were reviewed. The main endpoints were clinical performance for bladder cancer detection, recurrence or progression during NMIBC monitoring, and additional value compared to cytology and/or cystoscopy. RESULTS: Most studies on urinary biomarkers had a prospective design and high level of evidence. However, their results should be interpreted with caution given the heterogeneity among studies. Most of the biomarkers under study displayed higher detection sensitivity compared with cytology, but lower specificity. Some biomarkers may have clinical utility for NMIBC surveillance in patients with negative or equivocal cystoscopy or negative or atypical urinary cytology findings, and also for recurrence prediction. CONCLUSION: Urinary biomarkers might have a complementary place in bladder cancer diagnosis and NMIBC surveillance. However, their clinical benefit remains to be confirmed.

Partial nephrectomy in solitary kidneys: comparison between open surgery and robotic-assisted laparoscopy on perioperative and functional outcomes (UroCCR-54 study).

PURPOSE: The management of solitary kidney tumors is a surgical challenge, requiring irreproachable results on both oncological and functional outcomes. The goal of our study was to compare the perioperative results of robotic-assisted partial nephrectomy (RAPN) to open surgery in this indication. METHODS: We led a multicentric study based on the prospectively maintained French national database UroCCR. Patients who underwent partial nephrectomy on a solitary kidney between 1988 and 2020 were included. Clinical and pathological data were retrospectively analyzed. The main outcome of the study was the analysis of the variation of the estimated glomerular filtration rate (eGFR) calculated according to MDRD at 3, 6, 12, and 24 months depending on the chosen surgical approach. The secondary outcomes were the comparison of Trifecta success, perioperative complications, and length of hospital stay. RESULTS: In total, 150 patients were included; 68 (45%) in the RAPN group and 82 (55%) in the open surgery group. The two groups were comparable for all data. The variation of eGFR at 3, 6, 12, or 24 months was comparable without any significant difference between the 2 groups (p = 0.45). Trifecta was achieved in 40% of the patients in the RAPN group and 33% in the open group (p = 0.42). A significant difference was observed for the length of stay, 5 days for the robot group versus 9 days for the open surgery group (p < 0.0001). CONCLUSION: In our study, the surgical approach did not modify functional results and we noted a significant decrease in hospital stay and complications in the RAPN group. RAPN is a safe and efficient method for management of kidney tumors in solitary kidneys.

Late complications and 5 years outcomes of robotic partial nephrectomy in France: prospective assessment in the French Kidney Cancer Research Network (UroCCR 10).

PURPOSE: To describe the practice of robotic-assisted partial nephrectomy (RAPN) in France and prospectively assess the late complications and long-term outcomes. METHODS: Prospective, multicenter (n = 16), observational study including all patients diagnosed with a renal tumor who underwent RAPN. Preoperative, intraoperative, postoperative, and follow-up data were collected and stored in the French research network for kidney cancer database (UroCCR). Patients were included over a period of 12 months, then followed for 5 years. RESULTS: In total, 466 patients were included, representing 472 RAPN. The mean tumor size was 3.4 ± 1.7 cm, most of moderate complexity (median PADUA and RENAL scores of 8 [7-10] and 7 [5-9]). Indication for nephron-sparing surgery was relative in 7.1% of cases and imperative in 11.8%. Intraoperative complications occurred in 6.8% of patients and 4.2% of RAPN had to be converted to open surgery. Severe postoperative complications were experienced in 2.3% of patients and late complications in 48 patients (10.3%), mostly within the first 3 months and mainly comprising vascular, infectious, or parietal complications. At 5 years, 29 patients (6.2%) had chronic kidney disease upstaging, 21 (4.5%) were diagnosed with local recurrence, eight (1.7%) with contralateral recurrence, 25 (5.4%) with metastatic progression, and 10 (2.1%) died of the disease. CONCLUSION: Our results reflect the contemporary practice of French expert centers and is, to our knowledge, the first to provide prospective data on late complications associated with RAPN. We have shown that RAPN provides good functional and oncologic outcomes while limiting short- and long-term morbidity. TRIAL REGISTRATION: NCT03292549.

Oncocytoma on renal mass biopsy: is it still the same histology when surgery is performed? Results from UroCCR-104 study.

PURPOSE: To describe clinical features of patients with oncocytoma on renal biopsy (RMB), correlation with final histology on surgically treated patients, and predictive factors of discrepancy between RMB and final histology. METHODS: This was a retrospective study conducted in the framework of the UroCCR project (NCT03293563). All tumors with oncocytoma on RMB were selected and all pathological reports were reviewed. Patients with the RMB simultaneously performed with a focal treatment, synchronous bilateral tumors and ambiguous RMB report were excluded. Discrepancy between RMB and definitive histology was evaluated using a uni- and multivariable logistic regression analyses model. RESULTS: Overall, 119 tumors with oncocytoma on RMB, from 15 centers, were included. Of those, 54 (45.4%) had upfront surgery and 65 (54.6%) had active surveillance (AS). In renal masses with initial active surveillance, with a median follow-up of 28 months, 23 (19.3%) underwent surgery, 4 (3.4%) received focal treatment and 38 (31.9%) remained on AS. On final pathology, only 51 of the 75 surgically treated tumors (68.0%) had oncocytoma, while 24 presented malignant tumors (mainly chromophobe carcinoma (19.2%), and hybrid oncocytic/chromophobe tumor (HOCT) (6.8%)) leading to a discrepancy of 32.0% between RMB and final pathology. The only predictive factor of a discrepancy between RMB and definitive histology was a biopsy done outside of the center (Odds ratio: 3.22 [95%-confidence interval: 1.08-9.61], p = 0.03). CONCLUSION: Despite the increase of RMB in more and more centers, histologic discrepancy between RMB and definitive histology remains significant. This information should be discussed with patients and taken into consideration before treatment decision.

Nephrometry scores to predict oncological outcomes following partial nephrectomy (UroCCR Study 70).

PURPOSE: Partial nephrectomy (PN) for large or complex renal tumors can be difficult and associated with a higher risk of recurrence than radical nephrectomy. We aim to evaluate the clinical useful of nephrometry scores for predicting oncological outcomes in a large cohort of patients who underwent PN for renal cell carcinomas. METHODS: Our analysis included patients who underwent PN for renal cell carcinoma in 21 French academic centers (2010-2020). RENAL, PADUA, and SPARE scores were calculated based on preoperative imaging. Uni- and multivariate cox models were performed to identify predictors of recurrence-free survival and overall survival. The area under the curve (AUC) was used to identify models with the highest discrimination. Decision curve analyses (DCAs) determined the net benefit associated with their use. RESULTS: A total of 1927 patients were analyzed with a median follow-up of 32 months (14-45). RENAL score (p = 0.01), age (p = 0.002), histological type (p = 0.001), high nuclear grade (p = 0.001), necrotic component (p < 0.001), and positive margins (p = 0.005) were significantly related to recurrence in multivariate analyses. The discriminative performance of the 3 radiological scores was modest (65, 63, and 63%, respectively). All 3 scores showed good calibration, which, however, deteriorated with time. Decision curve analysis of the three models for the prediction of overall and recurrence-free survival was similar for all three scores and of limited clinical relevance. CONCLUSION: The association between nephrometry scores and oncological outcomes after NP is very weak. The use of these scores for predicting oncological outcomes in routine practice is therefore of limited clinical value.

Minimally invasive nephron-sparing treatments for T1 renal cell cancer in patients over 75 years: a comparison of outcomes after robot-assisted partial nephrectomy and percutaneous ablation.

PURPOSE: To compare the oncological and perioperative outcomes of robot-assisted partial nephrectomy (RPN) and percutaneous thermal ablation (PTA) for treatment of T1 renal cell cancer (RCC) in patients older than 75 years. MATERIALS AND METHODS: Retrospective national multicenter study included all patients older than 75 years treated for a T1 RCC by RPN or PTA between January 2010 and January 2021. Patients' characteristics, tumor data, and perioperative and oncological outcomes were compared. RESULTS: A total of 205 patients for 209 procedures (143 RPN and 66 PTA) were included. In the PTA group, patients were older (80.4 ± 3.7 vs. 79 ± 3.7 years (p = 0.01)); frailer (ASA score (2.43 ± 0.6 vs. 2.17 ± 0.6 (p < 0.01)); and more frequently had a history of kidney surgery (16.7% [11/66] vs. 5.6% [8/143] (p = 0.01)) than in the RPN group. Tumors were larger in the RPN group (2.7 ± 0.7 vs. 3.2 ± 0.9 cm (p < 0.01)). Operation time, length of hospital stay, and increase of creatinine serum level were higher in RPN (respectively 92.1 ± 42.7 vs. 150.7 ± 61.3 min (p < 0.01); 1.7 ± 1.4 vs. 4.2 ± 3.4 days (p < 0.01); 1.9 ± 19.3% vs. 10.1 ± 23.7 (p = 0.03)). Disease-free survival and time to progression were similar (respectively, HR 2.2; 95% CI 0.88-5.5; p = 0.09; HR 2.1; 95% CI 0.86-5.2; p = 0.1). Overall survival was shorter for PTA that disappeared after Cox adjusting model (HR 3.3; 95% CI 0.87-12.72; p = 0.08). CONCLUSION: Similar oncological outcomes are observed after PTA and RPN for T1 RCC in elderly patients. CLINICAL RELEVANCE STATEMENT: Robot-assisted partial nephrectomy and percutaneous thermal ablation have similar oncological outcomes for T1a kidney cancer in patients over 75 years; however, operative time, decrease in renal function, and length of hospital stay were lower with ablation. KEY POINTS: • After adjusting model for age and ASA score, similar oncological outcomes are observed after percutaneous thermal ablation and robot-assisted partial nephrectomy for T1 renal cell cancer in elderly patients. • Operation time, length of hospital stay, and increase of creatinine serum level were higher in the robot-assisted partial nephrectomy group.

StomaCare: quality of life impact after enhanced follow-up of ostomy patients by a home healthcare nursing service-a multicentre, randomized, controlled trial.

AIM: A stoma exposes patients to several complications which could impair their quality of life (QoL). In the last decade, the market for stoma therapy in France has evolved, with a significant increase in the activities of home health providers, meeting a need for patient follow-up and companionship. International studies have demonstrated the impact of the stoma therapist (ST) follow-up on the improvement of an ostomy patient's QoL. However, the impact of home stoma nurse management has not been analysed. In this context we would like to assess the added value on health-related QoL from the enhanced follow-up of ostomy patients by STs. METHODS: This is a randomized, controlled, open, national and multicentre trial (12 centres) which includes patients with an ostomy who benefit from either standard follow-up or from an enhanced and personalized follow-up with, in particular, regular consultations with an ST after discharge. The primary end-point is the 3-month QoL score obtained from the Stoma-QoL questionnaire. The secondary end-points are satisfaction of the care, comparison of QoL scores (Stoma-QoL and EuroQuol EQ-5D) and the economic gains by calculating the consumption of resources between the two arms. There will be a modified intention-to-treat analysis with 6-month follow-up in both study arms. DISCUSSION: The StomaCare trial will be the first randomized controlled study in France to evaluate the impact on QoL of an enhanced follow-up at home of ostomy patients by an ST.

Impact of Renal Cell Carcinoma Histological Variants on Recurrence After Partial Nephrectomy: A Multi-Institutional, Prospective Study (UROCCR Study 82).

BACKGROUND: The prognostic impact of renal cell carcinoma (RCC) morphotype remains unclear in patients who undergo partial nephrectomy (PN). Our objective was to determine the risk factors for recurrence after PN, including RCC morphotype. METHODS: Patients with RCC who had undergone PN were extracted from the prospective, national French database, UroCCR. Patients with genetic predisposition, bilateral or multiple tumours, and those who had undergone secondary totalization were excluded. Primary endpoint was 5-year, recurrence-free survival (RFS), and secondary endpoint was overall survival (OS). Risk factors for recurrence were assessed by multivariable Cox regression analysis. RESULTS: Overall, 2,767 patients were included (70% male; median age: 61 years [interquartile range (IQR) 51-69]). Most (71.5%) of the PN procedures were robot-assisted. Overall, 2,573 (93.0%) patients were recurrence free, and 74 died (2.7%). Five-year RFS was 84.9% (IQR 82.4-87.4). A significant difference in RFS was observed between RCC morphotypes (p < 0.001). Surgical margins (hazard ratio [HR] = 2.0 [95% confidence interval (CI): 1.3-3.2], p < 0.01), pT stage >1 (HR = 2.6 [95% CI: 1.8-3.7], p < 0.01]) and Fuhrmann grade >2 (HR = 1.9 [95% CI: 1.4-2.6], p < 0.001) were risk factors for recurrence, whereas chromophobe subtype was a protective factor (HR = 0.08 [95% CI: 0.01-0.6], p = 0.02). Five-year OS was 94.0% [92.4-95.7], and there were no significant differences between RCC subgroups (p = 0.06). The main study limitation was its design (multicentre national database), which may be responsible for declarative bias. CONCLUSIONS: Chromophobe morphotype was significantly associated with better RFS in RCC patients who underwent PN. Conversely, pT stage, Fuhrman group and positive surgical margins were risk factors for recurrence.

Using Contrast-Enhanced Ultrasound in Addition to Cross-Sectional Imaging for Indeterminate Renal Cysts May Lead to Overclassification in Bosniak III Category: A Case-Control Study.

INTRODUCTION: Indeterminate renal cysts may require several imaging modalities before clinical decision. The aim of this study was to investigate the effect of the imaging modality used to characterize indeterminate renal cysts on the pathological findings after surgical resection. METHODS: From our institutional database, we identified all patients surgically treated for Bosniak III renal masses between January 2008 and January 2018. All complex renal cysts were characterized with a combination of computed tomography (CT) and/or magnetic resonance imaging (MRI), and/or contrast-enhanced ultrasound (CEUS) and discussed during a multidisciplinary tumor board. Potential association between clinical/radiological characteristics and the pathological findings were investigated, using univariate and multivariate analyses. RESULTS: Of the 52 renal cystic lesions surgically removed, with a preoperative diagnosis of Bosniak III renal cyst, 19 (37%) were malignant and 33 (63%) were benign. The proportion of malignant lesions decreased from 47% when the renal cyst was characterized with cross-sectional imaging (CT and/or MRI) to 17% when the diagnosis required CEUS in addition to cross-sectional imaging. In multivariate analysis, prior history of renal cell carcinoma was associated with a higher risk of malignancy (p = 0.016) and diagnosis made with CEUS was associated with a lower risk of malignancy (p = 0.040). CONCLUSION: We found that using CEUS in addition to cross-sectional imaging to characterize indeterminate renal cysts tends to redefine Bosniak III as lesions with a lower risk of malignancy and can lead to overclassification.

Evaluation of a free 3D software for kidney stones' surgical planning: "kidney stone calculator" a pilot study.

INTRODUCTION: Kidney Stone Calculator (KSC) is a free, three-dimensional (3D) planning software for flexible ureteroscopy(fURS) with Holmium:YAG(Ho:YAG) endocorporeal lithotripsy (EL). KSC provides the stone volume (SV) and expected duration of lithotripsy (ExDL) estimations based on non-enhanced-CT scan (NECT) DICOM series. We aimed to provide a preclinical and clinical evaluation of KSC. PATIENTS AND METHODS: A preclinical evaluation measured the SV by three operators (resident, endourology expert and research engineer) among 17 NECT cases. Between January and March 2020, a multicentric, prospective, observational double-blind clinical evaluation was conducted in patients presenting with renal stones treated with Ho:YAG-EL during fURS and preoperative NECT. Demographic and surgical data were collected. The primary endpoint was a significant median difference between ExDL and EffectiveDL (EfDL). Second, efficiency (J/mm3) and efficacy (mm3/min) ratios were calculated. RESULTS: The preclinical evaluation showed no significant difference in the SV measurements among operators (p > 0.05). Pearson and Kendall coefficients of 0.99 and 0.98, respectively, were found. Twenty-six patients were included in the clinical evaluation, with a median age of 55 years. In 66% of cases, there was a single stone located in the lower pole, with a density > 1000 Hounsfield Unit observed in 42% and 85% of cases. A 14% [Q1-Q3 (5.4-24.8); p = 0.36] median difference between ExDL and EfDL was noted, which was greater in the case of lower pole stones with no possible relocation (p = 0.008). Median values of 17.6 J/mm3 and 0.4 (0.32-0.56) mm3/s EL were also noted. CONCLUSIONS: Kidney Stone Calculator is a reproducible and accurate software that allows for an estimation of the stone burden and provides an ExDL for URSf. Defining the influencing factors of EL will improve its ExDL.

Persistent orchialgia after laparoscopic living-donor nephrectomy: an underestimated complication requiring information adjustment.

PURPOSE: Laparoscopic living-donor nephrectomy (LLDN) is the gold-standard procedure for kidney procurement. Ipsilateral orchialgia has barely been described. Some authors reported that ligation of gonadal vein (GV) above iliac vessel bifurcation could prevent orchialgia. We aimed to assess incidence and duration of orchialgia after LLDN in male donors despite distal ligation of GV. METHODS: Patients who underwent LLDN from 2014 to 2017 were included. Standard procedure consisted in distal ligation of GV, close to the renal vein confluence and proximal ureteral ligation. Patients' demographics, per-operative data, and post-operative consultation reports were retrospectively reviewed. Orchialgia and scrotal symptoms were assessed through a non-validated questionnaire by phone interview. RESULTS: Sixty-nine donors were included. Orchialgia incidence and testicular swelling were 31.9% (n = 22) and 15.9% (n = 11), respectively. Median symptom duration was 15.5 months. Orchialgia led to medical consultation in 41.7% (n = 10) of cases. All patients declared having been informed, prior to donation, about possible residual pain but not specifically orchialgia. CONCLUSION: Orchialgia after LLDN affects more than 30% of donors, despite distal ligation of GV and led less than 50% of them to medical consultation, suggesting a large underestimation in clinical practice. Emphasis should be put on this complication during pre-donation information.

PD-L1 expression and pattern of immune cells in pre-treatment specimens are associated with disease-free survival for HR-NMIBC undergoing BCG treatment.

PURPOSE: To assess the association between PD-L1 expression and disease-free survival (DFS) in High-Risk Non-Muscle Invasive Bladder Cancer (HR-NMIBC) patients treated with intravesical Bacillus Calmette-Guerin (BCG) instillations (IBI). METHODS: Retrospective study in five French centres between 2001 and 2015. Participants were 140 patients with histologically confirmed HR-NMIBC. All patients received induction and maintenance IBI. Pathological stage/grade, concomitant carcinoma in situ, lesion number and tumour size were recorded. CD3, CD8 and PD-L1 expression in tumour cells and in T cells in the tumour microenvironment (TME) was determined immunohistochemically. Median follow-up was 54.2 months. The primary outcome measure was DFS. Univariable and multivariable analyses were performed using the log rank test and Cox proportional hazards model. RESULTS: Of the 140 NMIBC, 52 (37.1%) were Ta, 88 (62.9%) were T1 and 100% were high grade. Median number of maintenance IBI was six (range 1-30). Twenty-five (17.9%) patients had recurrence/progression. In multivariable analysis, age (HR 1.07 [95% CI 1.02-1.13], p = 0.009), PD-L1 expression in tumour cells (HR per 10 units = 1.96 [95% CI 1.28-3.00], p = 0.02) and CD3/CD8 ratio (HR per 10 units = 3.38 [95% CI 1.61-7.11], p = 0.01) were significantly associated with DFS. However, using the cut-off corresponding for each PD-L1 antibodies, PD-L1 + status was not associated with DFS. CONCLUSION: Despite an association between PD-L1 expression and BCG failure in HR-NMIBC, the PD-L1 + status was not a prognostic factor in the response of BCG. Moreover, we confirmed the key role played by the IC within the microenvironment in BCG treatment. These findings highlighted the rationale to combine BCG and PD-L1/PD-1 antibodies in early bladder cancer.

A kidney discard decision strategy based on zero-time histology analysis could lead to an unjustified increase in the organ turndown rate among ECD.

The utility of zero-time kidney biopsies (KB) in deciding to accept expanded criteria donor (ECD) kidneys remains controversial. However, zero-time histology is one of the main causes for discarding kidneys in the United States. In a single-centre study, we examined the utility and impact on outcome of the use of frozen section zero-time KB among ECD. Ninety-two zero-time KB were analysed for accept/discard decision between 2005 and 2015 among ECD. 53% of kidneys were rejected after zero-time KB analysis; there was no difference in individual clinical and biological data between accepted/rejected groups. However, histology of rejected kidneys showed more sclerotic glomeruli (20% vs. 8%; P < 0.001), increased interstitial fibrosis (1.25 ± 0.12 vs. 0.47 ± 0.09; P < 0.0001), more arteriosclerosis (2.14 ± 0.17 vs. 1.71 ± 0.11; P = 0.0032) and arteriolar hyalinosis (2.15 ± 0.12 vs. 1.55 ± 0.11; P = 0.0006). Using propensity score matching, we generated a group of 42 kidney allograft recipients who received a transplant matched for donor zero-time histology and clinical characteristics with donors whose kidneys were rejected. Interestingly, their 1- and 5-year graft survival and function were similar to the global cohort of ECD recipients. In conclusion, when performed, zero-time KB was a decisive element for kidney discard decision. However, adverse zero-time histology was not associated with poorer graft survival and kidney function among ECD.

Effectiveness of Transurethral Resection plus Systemic Chemotherapy as Definitive Treatment for Muscle Invasive Bladder Cancer in Population Level Data.

PURPOSE: We investigated the characteristics and outcomes of patients with muscle invasive bladder cancer treated with transurethral resection plus chemotherapy alone in a large observational cohort reflecting the continuum of practice settings in the United States. MATERIALS AND METHODS: In the National Cancer Database from 2004 to 2015 we identified 1,538 patients treated with transurethral resection plus multi-agent chemotherapy as definitive treatment of cT2-T4aN0M0 urothelial carcinoma of the bladder. For comparison purposes we included in study 17,866 patients treated with radical cystectomy with or without perioperative chemotherapy. Baseline characteristics were compared between the 2 groups by multivariable logistic regression. Treatment outcomes were assessed using Kaplan-Meier analysis and a Cox regression model. RESULTS: On multivariate analysis several variables, including patient demography (older age, African American race, prior malignancy and lack of insurance), tumor characteristics (higher cT stage) and facility type (nonacademic facilities and lower radical cystectomy volume) were associated with a higher probability of transurethral resection plus chemotherapy for muscle invasive bladder cancer compared to the standard of care. Two and 5-year survival rates in all patients treated with transurethral resection plus chemotherapy were 49.0% and 32.9%, and in patients with cT2 disease the rates were 52.6% and 36.2%, respectively. CONCLUSIONS: This large population level cohort of unselected patients shows that long-term survival can be achieved in a subset of patients treated with transurethral resection plus chemotherapy alone for muscle invasive bladder cancer. However, the best candidates for this approach remain to be defined. Ongoing clinical trials are now being launched to evaluate the ability of biomarkers to accurately select patients who could be treated with this bladder sparing strategy.

Biopsy Core Features are Poor Predictors of Adverse Pathology in Men with Grade Group 1 Prostate Cancer.

PURPOSE: Active surveillance is often restricted to patients with low risk prostate cancer who have 3 or fewer positive cores. We aimed to identify predictors of adverse pathology results for low risk prostate cancer treated with radical prostatectomy and determine whether a threshold number of positive cores could help the decision process for active surveillance. MATERIALS AND METHODS: A total of 3,359 men with low risk prostate cancer underwent radical prostatectomy between January 2000 and August 2016. We analyzed the relationship between biopsy core features and adverse pathology at radical prostatectomy, defined as Grade Group 3 or greater, seminal vesicle invasion or lymph node involvement. RESULTS: Of the 171 cases (5.1%) with adverse pathology findings at radical prostatectomy 144 (4.3%) were upgraded to Grade Group 3 or greater, 31 (0.9%) had seminal vesicle invasion and 15 (0.4%) had lymph node involvement. Prostate specific antigen and patient age were the only predictors of adverse pathology results. There was no significant association with the number of positive cores, the total mm of cancer or the maximum percent of cancer in any core. When we expanded the definition of adverse pathology to include Grade Group 2 and extraprostatic extension, the association between core features and outcome was statistically significant but clinically weak, and with no evidence of threshold effects. CONCLUSIONS: There is little basis for excluding patients with otherwise low risk prostate cancer on biopsy from active surveillance based on criteria such as the number of positive cores or the maximum cancer involvement of biopsy cores.