Multi-ancestry genome-wide association study of kidney cancer identifies 63 susceptibility regions.

Here, in a multi-ancestry genome-wide association study meta-analysis of kidney cancer (29,020 cases and 835,670 controls), we identified 63 susceptibility regions (50 novel) containing 108 independent risk loci. In analyses stratified by subtype, 52 regions (78 loci) were associated with clear cell renal cell carcinoma (RCC) and 6 regions (7 loci) with papillary RCC. Notably, we report a variant common in African ancestry individuals ( rs7629500 ) in the 3' untranslated region of VHL, nearly tripling clear cell RCC risk (odds ratio 2.72, 95% confidence interval 2.23-3.30). In cis-expression quantitative trait locus analyses, 48 variants from 34 regions point toward 83 candidate genes. Enrichment of hypoxia-inducible factor-binding sites underscores the importance of hypoxia-related mechanisms in kidney cancer. Our results advance understanding of the genetic architecture of kidney cancer, provide clues for functional investigation and enable generation of a validated polygenic risk score with an estimated area under the curve of 0.65 (0.74 including risk factors) among European ancestry individuals.

[Current state of knowledge of urology residents and fellows on the neuro-urological management of spina bifida patients in France]. / État des lieux des connaissances des internes et chefs de clinique d'urologie sur la prise en charge neuro-urologique des patients spina bifida en France.

OBJECTIVE: To assess the current knowledge of French urology residents and fellows about neurogenic lower urinary tract dysfunction and their management in patients with spina bifida. MATERIAL AND METHOD: A 7-question questionnaire, covering the responder's experience and the various stages in the neuro-urological management of spina bifida, was drafted by an expert urologist. Responses were collected within 5days of being e-mailed to members of the Association française des urologues en formation (AFUF), and a descriptive analysis was carried out. RESULTS: Of the 448 members, 155 completed the questionnaire. Of the participants, 83.8% said they knew the definition of spina bifida, and 76.8% had already had to care for a spina bifida patient. Of the participants, 48.4% correctly estimated the number of spina bifida patients in France. Neurogenic lower urinary tract dysfunction to look for and the specificities of management seemed to have been acquired by a majority of respondents (correct response rates of 70.7% and 75.4%, respectively), unlike the extra-urological aspects (53.9%), and the choice of examinations useful for the initial work-up and follow-up (55.8%). CONCLUSION: While the expected neurogenic lower urinary tract dysfunction and the specificities of therapeutic management of spina bifida patients appear to be well known to urologists in training, knowledge of extra-urological symptoms and the choice of examinations could be improved. These results could be used to adjust the teaching given to French urologists in training on the urological management of spina bifida patients. LEVEL OF EVIDENCE: Grade 4.

UroPredict: Machine learning model on real-world data for prediction of kidney cancer recurrence (UroCCR-120).

Renal cell carcinoma (RCC) is most often diagnosed at a localized stage, where surgery is the standard of care. Existing prognostic scores provide moderate predictive performance, leading to challenges in establishing follow-up recommendations after surgery and in selecting patients who could benefit from adjuvant therapy. In this study, we developed a model for individual postoperative disease-free survival (DFS) prediction using machine learning (ML) on real-world prospective data. Using the French kidney cancer research network database, UroCCR, we analyzed a cohort of surgically treated RCC patients. Participating sites were randomly assigned to either the training or testing cohort, and several ML models were trained on the training dataset. The predictive performance of the best ML model was then evaluated on the test dataset and compared with the usual risk scores. In total, 3372 patients were included, with a median follow-up of 30 months. The best results in predicting DFS were achieved using Cox PH models that included 24 variables, resulting in an iAUC of 0.81 [IC95% 0.77-0.85]. The ML model surpassed the predictive performance of the most commonly used risk scores while handling incomplete data in predictors. Lastly, patients were stratified into four prognostic groups with good discrimination (iAUC = 0.79 [IC95% 0.74-0.83]). Our study suggests that applying ML to real-world prospective data from patients undergoing surgery for localized or locally advanced RCC can provide accurate individual DFS prediction, outperforming traditional prognostic scores.

Cut-off time for surgery and prediction of orchiectomy in spermatic cord torsion: a retrospective multicentric study over 15 years.

PURPOSE: Cut-off time to avoid orchiectomy relies on small series of patients. The objective was to determine the cut-off time to avoid orchiectomy in torsion of the spermatic cord in a large cohort. METHODS: We performed a retrospective multicenter study (TORSAFUF cohort) of patients with suspected spermatic cord torsion between 2005 and 2019. All patients aged > 12 years who were suspected of having a torsion of the spermatic cord in 14 University Hospitals in France were included (n = 2986). Patients for whom data on pain duration were not available (n = 923) or for whom the final diagnosis was not torsion of the spermatic cord (n = 807) were excluded. The primary outcome was orchiectomy. The secondary outcomes were testicular survival time and the prediction of orchiectomy with the duration of pain. RESULTS: 1266 patients were included with an orchiectomy rate of 12% (150 patients). The mean age was 21.5 years old in the salvage group and 23.7 years old in the orchiectomy group (p = 0.01), respectively. The median time from the onset of pain to surgery was 5.5 (IQR = 5) hours in the salvage group and 51.1 (IQR = 70) hours in the orchiectomy group (p < 0.0001). The risk of orchiectomy increased after a time cut-off of 6 h 30. A delay of 15 h 30 in pain duration was found to predict orchiectomy (sensitivity: 0.81; specificity: 0.87). CONCLUSIONS: Pain duration can predict the probability of salvaging the testicles and performing orchiectomy. Rapid intervention should be recommended, regardless of the time elapsed from the onset of pain.

Percutaneous tumor ablation versus image guided robotic-assisted partial nephrectomy for cT1b renal cell carcinoma: a comparative matched-pair analysis (UroCCR 80).

BACKGROUND: Partial nephrectomy (PN) is the gold standard treatment for cT1b renal tumors. Percutaneous guided thermal ablation (TA) has proven oncologic efficacy with low morbidity for the treatment of small renal masses (<3 cm). Recently, 3D image-guided robot-assisted PN (3D-IGRAPN) has been described, and decreased perioperative morbidity compared to standard RAPN has been reported. Our objective was to compare two minimally invasive image-guided nephron-sparing procedures (TA vs. 3D-IGRAPN) for the treatment of cT1b renal cell carcinomas (4.1-7 cm). METHODS: Patients treated with TA and 3D-IGRAPN for cT1b renal cell carcinoma, prospectively included in the UroCCR database (NCT03293563), were pair-matched for tumor size, pathology, and RENAL score. The primary endpoint was the local recurrence rate between the two groups. Secondary endpoints included metastatic evolution, perioperative complications, decrease in renal function, and length of hospitalization. RESULTS: A total of 198 patients were included and matched into two groups of 72 patients. The local recurrence rate was significantly higher in the TA group than that in the 3D-IGRAPN group (4.2% vs. 15.2%, P=0.04). Metastatic evolution and perioperative outcomes such as major complications, eGFR decrease, and length of hospitalization did not differ significantly between the two groups. CONCLUSIONS: 3D-IGRAPN resulted in a significantly lower local recurrence rate and comparable rates of complications and metastatic evolution compared with thermal ablation.

Can Simplified PADUA Renal (SPARE) Nephrometry scoring system help predict renal function outcomes after robot-assisted partial nephrectomy? (UroCCR study 93).

BACKGROUND: The SPARE Nephrometry Score (NS) is described as easier to implement than the RENAL and PADUA NSs, currently more widely used. Our objective was to compare the accuracy of SPARE NS in predicting renal function outcomes following RAPN. METHODS: A multicentric retrospective study was conducted using French kidney cancer network (UroCCR, NCT03293563) database. All patients included had RAPN for cT1 renal tumors between May 2010 and March 2021. SPARE was compared to RENAL, PADUA and Tumor Size to predict postoperative acute kidney injury (AKI), chronic kidney disease (CKD) upstaging, de novo CKD at 3-6 months follow-up and Trifecta failure. The ability of the different NSs and tumor size to predict renal function outcomes was evaluated using uni- and multivariate logistic regression models. RESULTS: According to our study criteria, 1171 patients were included. Mean preoperative tumor size and estimated glomerular filtration rate (eGFR) were 3.4±1.4 cm and 85.8 mL/min/1.73 m2. In total, 266 (22.7%), 87 (7.4%), 94 (8%), and 624 (53.3%) patients had AKI, de novo CKD, CKD upstaging, and Trifecta failure, respectively. In multivariate analysis, all three NSs and tumor size were independent predictors of AKI, CKD de novo, CKD upgrade and Trifecta failure. There was no significant difference between all three NS and tumor sizes in predicting renal function outcomes. CONCLUSIONS: SPARE Score seems to be a valid alternative to predict renal function outcomes after RAPN. Nevertheless, in our study, tumor size was as accurate as NSs in predicting postoperative outcomes and, therefore, seems to be the logical choice for surgical decisions.

Clinical trial protocol for P-NeLoP: a randomized controlled trial comparing the feasibility and outcomes of robot-assisted partial nephrectomy with low insufflation pressure using AirSeal versus standard insufflation pressure (UroCCR no. 85 study).

Robot-assisted partial nephrectomy (RAPN) is the standard of care for small, localized kidney tumors. This surgery is conducted within a short hospital stay and can even be performed as outpatient surgery in selected patients. In order to allow early rehabilitation of patients, an optimal control of postoperative pain is necessary. High-pressure pneumoperitoneum during surgery seems to be the source of significant pain during the first hours postoperatively. Our study is a prospective, randomized, multicenter, controlled study which aims to compare post-operative pain at 24 h between patients undergoing RAPN at low insufflation pressure (7 mmHg) and those operated on at standard pressure (12 mmHg) using the AirSeal system.This trial is registered in the US National Library of Medicine Trial Registry (NCT number: NCT05404685).

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.

Three Dimensional Printing Technology Used to Create a High-Fidelity Ureteroscopy Simulator: Development and Validity Assessment (Rein-3D-Print-UroCCR-39).

OBJECTIVE: To create and assess the validity of a high-fidelity, three dimensional (3D) printed, flexible ureteroscopy simulator resulting from a real case. METHODS: A patient's CT scan was segmented to obtain a 3D model in .stl format, including the urinary bladder, ureter and renal cavities. The file was printed and a kidney stone was introduced into the cavities. The simulated surgery consisted of monobloc stone extraction. Nineteen participants split into 3 groups according to their level (6 medical students, 7 residents and 6 urology fellows) performed the procedure twice at a 1-month interval. They were rated according to a global score and a task-specific score, based on an anonymized, timed video recording. RESULTS: Participants demonstrated a significant improvement between the 2 assessments, both on the global score (29.4 vs 21.9 points out of 35; P < .001) and the task-specific score (17.7 vs 14.7 points out of 20; P < .001) as well as procedure time (498.5 vs 700 seconds; P = .001). Medical students showed the greatest progress for the global score (+15.5 points (mean), P = .001) and the task-specific score (+6.5 points (mean), P < .001). 69.2% of participants considered the model as visually quite realistic or highly realistic and all of them judged it quite or extremely interesting for intern training purposes. CONCLUSION: Our 3D printed ureteroscopy simulator was able to enhance the progress of medical students who are new to endoscopy, whilst being valid and reasonably priced. It could become part of a training program in urology, in line with the latest recommendations for surgical education.

Nurse-led coordinated surgical care pathways for cost optimization of robotic-assisted partial nephrectomy: medico-economic analysis of the UroCCR-25 AMBU-REIN study.

PURPOSE: Robot-assisted partial nephrectomy (RAPN) reduces morbidity, enabling development of Enhanced Recovery After Surgery (ERAS) and day-case protocols. Additional financial costs limit its integration into clinical practice. We evaluated the medico-economic impact of RAPN using a nurse-led coordinated pathway of care (NLC-RAPN). METHODS: All tumor RAPNs performed in 2017 were prospectively included in nurse-led protocols: NP-RAAC (ERAS) or Ambu-Rein (day case). Clinico-biological and pathological data were prospectively collected within the French Research Network for Kidney Cancer database (NCT03293563). Estimated costs were compared to "average" patients at the national level operated by open partial nephrectomy (OPN) or RAPN, using data from the 2017 French hospital discharge database and the national cost scale. RESULTS: The NLC-RAPN cohort (n = 151) included 27 (18%) outpatients and the average hospital length of stay (LOS) was 2.4 days. In the national control cohorts for OPN (n = 2475) and RAPN (n = 3529), the average LOS were 8.0 and 5.2 days, respectively. The mean incomes per group were €7607 for NLC-RAPN, €9813 for OPN, and €8215 for RAPN. The mean daily cost of stay was €659 for NLC-RAPN, €838 for OPN, and €725 for RAPN. The overall cost for NLC-RAPN was €6594, €8733 for OPN, and €8763 for RAPN. The best operational margin was obtained for day-case NLC-RAPN (€1967). CONCLUSION: Combining RAPN with nurse-led coordinated pathways of care led to a shorter hospital stay and reduced costs versus OPN. This may facilitate the economic sustainability of robotic assistance for hospitals where the extra cost is not covered by the healthcare system.

A survey of augmented reality methods to guide minimally invasive partial nephrectomy.

INTRODUCTION: Minimally invasive partial nephrectomy (MIPN) has become the standard of care for localized kidney tumors over the past decade. The characteristics of each tumor, in particular its size and relationship with the excretory tract and vessels, allow one to judge its complexity and to attempt predicting the risk of complications. The recent development of virtual 3D model reconstruction and computer vision has opened the way to image-guided surgery and augmented reality (AR). OBJECTIVE: Our objective was to perform a systematic review to list and describe the different AR techniques proposed to support PN. MATERIALS AND METHODS: The systematic review of the literature was performed on 12/04/22, using the keywords "nephrectomy" and "augmented reality" on Embase and Medline. Articles were considered if they reported surgical outcomes when using AR with virtual image overlay on real vision, during ex vivo or in vivo MIPN. We classified them according to the registration technique they use. RESULTS: We found 16 articles describing an AR technique during MIPN procedures that met the eligibility criteria. A moderate to high risk of bias was recorded for all the studies. We classified registration methods into three main families, of which the most promising one seems to be surface-based registration. CONCLUSION: Despite promising results, there do not exist studies showing an improvement in clinical outcomes using AR. The ideal AR technique is probably yet to be established, as several designs are still being actively explored. More clinical data will be required to establish the potential contribution of this technology to MIPN.

Can Pre-Operative Neutrophil-to-Lymphocyte Ratio (NLR) Help Predict Non-Metastatic Renal Carcinoma Recurrence after Nephrectomy? (UroCCR-61 Study).

Recent studies suggested that the neutrophil-to-lymphocyte ratio (NLR) could play a key role in tumor initiation, progression and response to treatments. The main objective was to assess the prognostic value of the pre-operative NLR on recurrence-free survival (RFS) in patients with non-hereditary localized renal cell carcinoma. From the UroCCR database (NCT03293563), factors influencing the disease recurrence of consecutive patients who underwent nephrectomy for cT1-T4 N0M0 were analyzed using multi-variate cox regression and log-rank methods. We included 786 patients, among which 135 (17.2%) experienced a recurrence at a median time of 23.7 [8.5-48.6] months. RFS for patients with a pre-operative NLR of <2.7 was 94% and 88% at 3 and 5 years, respectively, versus 76% and 63% for patients with a NLR of ≥2.7 (p < 0.001, log-rank test). To predict the risk of post-operative recurrence, the NLR was combined with the UCLA integrated staging system (UISS), and we defined four groups of the UroCCR-61 predictive model. The RFS rates at 3 and 5 years were 100% and 97% in the very-low-risk group, 93% and 86% in the low-risk group, 78% and 68% in the intermediate-risk group and 63% and 46% in the high-risk group (p < 0.0001). The pre-operative NLR seems to be an inexpensive and easily accessible prognostic bio-marker for non-metastatic RCCs.

Feasibility of salvage robotic partial nephrectomy after ablative treatment failure (UroCCR-62 study).

BACKGROUND: Ablative therapies (AT) are increasingly being offered to patients with kidney tumors. In cases of failure or local relapse, salvage surgery may be required. Such procedures often require an open approach, are difficult and have received little attention in the literature. We aim to evaluate the feasibility of salvage robot-assisted partial nephrectomy (sRAPN) after AT. METHODS: We conducted a monocentric retrospective study of all patients who benefited from sRAPN. Clinical data were collected prospectively after written consent in the French UroCCR database. RESULTS: Between 2013 and 2020, 724 RAPN were performed in our center; of these, 11 patients underwent salvage RAPN and four (36.4%) had an imperative indication for a solitary kidney. The median patient age was 54 (49-72) years, median preoperative glomerular filtration rate (GFR) was 65.5 (42.9-88.4) mL/min/1.73 m2, and median tumor diameter was 34 (16-38) mm. Extensive perinephric fibrosis was present in 90.9% of cases. Postoperative complications occurred in 36.4% of patients, including major complications in 18.2%. The median GFR at three months (56.8 [45.9-63.9] mL/min/1.73 m2) and at last follow-up (52.1 [45.85-68.3] mL/min/1.73 m2) were not significantly different to the preoperative GFR (P=0.51 and P=0.65, respectively). During follow-up (median 12 months), three patients (all with Von Hippel Lindau disease) developed a recurrence, but none were on the sRAPN site. CONCLUSIONS: Our series of sRAPN following AT failure confirms that such surgery is feasible with good functional and oncological results. However, these surgeries remain difficult, are associated with significant complication rate and should be performed in expert centers.

Torsion of the spermatic cord in adults: a multicenter experience in adults with surgical exploration for acute scrotal pain with suspected testicular torsion.

Acute scrotal pain (ASP) requiring surgical exploration is common in the pediatric population, but little has been reported on this subject with regard to the adult population. The aim of this study was to investigate the demographic and clinical characteristics and outcomes of scrotal explorations performed on adult patients. Patients over 21 years of age who underwent surgical exploration for ASP with suspected testicular torsion (TT) at 14 French hospitals between January 2005 and December 2019 were included in this study. The main outcome measures were demographic characteristics, pathology found during scrotal exploration, and perioperative outcomes. Logistic regression was used to perform univariate and multivariate analyses to identify predictors of TT. Data for 1329 men were analyzed. The median age was 30 (interquartile range [IQR]: 25-35; range: 21-89) years. Regarding the clinical examination, 867 (65.2%) patients presented with an elevation of the testicle, 613 (46.1%) patients with scrotal edema or erythema, and 211 (15.9%) patients with nausea or vomiting. Operative findings identified TT in only 684 (51.5%) patients, epididymo-orchitis in 112 (8.4%) patients, a tumor in 16 (1.2%) patients, and no causes in 475 (35.7%) patients. Orchiectomy for nonviable testes was required in 101 (7.6%) patients. In multivariate analysis, an elevation of the testicle, erythema/swelling, and the presence of nausea/vomiting were found to be associated with the occurrence of TT. Testicular torsion is not exclusive to children and adolescents, so must be considered in males of any age with acute scrotal findings. However, one-third of scrotal explorations in adults did not lead to a diagnosis.

Contralateral Orchiopexy at the Time of Urgent Scrotal Exploration-Is It Safe? A Propensity Score Matched Analysis from the TORSAFUF Cohort.

PURPOSE: We evaluate the safety of immediate contralateral orchiopexy (ICLO) at the time of scrotal exploration for testicular torsion suspicion. MATERIALS AND METHODS: Patient data were retrieved from the TORSAFUF cohort project, which is a multicenter national study conducted at 14 academic French hospitals between 2005 and 2019. Each patient who underwent surgical exploration for testicular torsion suspicion was included. The primary study outcome was the safety of ICLO compared to ipsilateral scrotal exploration alone. The primary outcome of interest was the complication rate within 90 days of surgery. The end point was planned before data collection. RESULTS: Overall, 2,775 patients were included, of whom 1,554 (56%) underwent ICLO. After propensity score matching and multivariable analysis, ICLO was associated with a higher complication rate (OR 1.51, 95% CI 1.1-2.1, p=0.01), especially a higher rate of hematoma (OR 2.9, 95% CI 1.3-6.6, p=0.01), and delayed wound healing (OR 3.0, 95% CI 1.8-5.2, p <0.001). CONCLUSIONS: At the time of scrotal exploration for acute scrotum, ICLO was associated with an increased postoperative complication rate, with a particular increase in hematoma, and delayed wound healing. ICLO should not be performed systematically.