Open versus robotic partial nephrectomy in obese patients: a multi-institutional propensity score-matched analysis (UroCCR 43-Robese study).

INTRODUCTION: There is limited evidence on the outcomes of robotic partial nephrectomy (RPN) and open partial nephrectomy (OPN) in obese patients (BMI ≥ 30 kg/m2). In this study, we aimed to compare perioperative and oncological outcomes of RPN and OPN. METHODS: We relied on data from patients who underwent PN from 2009 to 2017 at 16 departments of urology participating in the UroCCR network, which were collected prospectively. In an effort to adjust for potential confounders, a propensity-score matching was performed. Perioperative outcomes were compared between OPN and RPN patients. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: Overall, 1277 obese patients (932 robotic and 345 open were included. After propensity score matching, 166 OPN and 166 RPN individuals were considered for the study purposes; no statistically significant difference among baseline demographic or tumor-specific characteristics was present. A higher overall complication rate and major complications rate were recorded in the OPN group (37 vs. 25%, p = 0.01 and 21 vs. 10%, p = 0.007; respectively). The length of stay was also significantly longer in the OPN group, before and after propensity-score matching (p < 0.001). There were no significant differences in Warm ischemia time (p = 0.66), absolute change in eGFR (p = 0.45) and positive surgical margins (p = 0.12). At a median postoperative follow-up period of 24 (8-40) months, DFS and OS were similar in the two groups (all p > 0.05). CONCLUSIONS: In this study, RPN was associated with better perioperative outcomes (improvement of major complications rate and LOS) than OPN. The oncological outcomes were found to be similar between the two approaches.

The Impact of Histological Variants on Oncological Outcomes After Surgical Resection of a Nonmetastatic Renal Cell Carcinoma with Tumor Thrombus: A Multi-institutional Study.

Background: There is no definitive evidence of the prognosis impact of histological variants (HVs) in patients who undergo surgical resection of a nonmetastatic renal cell carcinoma (nm-RCC) with venous tumor thrombus (TT). Objective: To investigate the impact of HVs on the prognosis of patients with nm-RCC with TT after radical surgery. Design setting and participants: Patients who underwent radical nephrectomy with the removal of the venous TT for an nm-RCC were included in a retrospective study. Outcome measurements and statistical analysis: Three groups were identified: clear cell (ccRCC), papillary (pRCC), and chromophobe (chRCC) RCC. The primary outcome measures (disease-free and overall survival [OS]) were assessed using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate Cox proportional hazard models were used to study the impact of HVs on survival. Results and limitations: A total of 873 patients were included. The histological subtypes were distributed as follows: ccRCC in 780 cases, pRCC in 58 cases, and chRCC in 35 cases. At the time of data analysis, 612 patients were recurrence free and 228 had died. A survival analysis revealed significant differences in both OS and recurrence-free survival across histological subtypes, with the poorest outcomes observed in pRCC patients (p < 0.05). In a multivariable analysis, pRCC was independently associated with worse disease-free survival and OS (hazard ratio [HR]: 1.71; p = 0.01 and HR: 1.24; p = 0.04), while chRCC was associated with more favorable outcomes than ccRCC (HR: 0.05; p < 0.001 and HR: 0.02; p < 0.001). A limitation of the study is its retrospective nature. Conclusions: In this multicentric series, HVs appeared to impact the medium-term oncological prognosis of kidney cancer with TT. Patient summary: This study investigated the differences in oncological outcomes among histological variants (clear cell, papillary, and chromophobe) in a cohort of nonmetastatic renal cell carcinoma patients with venous tumor thrombus extension. We observed that these histological variants within this specific subgroup exhibit distinct outcomes, with papillary renal cell carcinoma being associated with the worst prognosis.

Robotic YV plasty outcomes for bladder neck contracture vs. vesico-urethral anastomotic stricture.

PURPOSE: To compare the outcomes of patients undergoing robotic YV plasty for bladder neck contracture (BNC) vs. vesico-urethral anastomotic stricture (VUAS). METHODS: A retrospective study included male patients who underwent robotic YV plasty for BNC after endoscopic treatment of BPH or VUAS between August 2019 and March 2023 at a single academic center. The primary assessed was the patency rate at 1 month post-YV plasty and during the last follow-up visit. RESULTS: A total of 21 patients were analyzed, comprising 6 in the VUAS group and 15 in the BNC group. Patients with VUAS had significantly longer operative times (277.5 vs. 146.7 min; p = 0.008) and hospital stay (3.2 vs. 1.7 days; p = 0.03). Postoperative complications were more common in the VUAS group (66.7% vs. 26.7%; p = 0.14). All patients resumed spontaneous voiding postoperatively. Five patients (23.8%) who developed de novo stress urinary incontinence had already an AUS (n = 1) or required concomitant AUS implantation (n = 3), all of whom were in the VUAS group (83.3% vs. 0%; p < 0.0001). The proportion of patients improved was similar in both groups (PGII = 1 or 2: 83.3% vs. 80%; p = 0.31). Stricture recurrence occurred in 9.5% of patients in the whole cohort, with no significant difference between the groups (p = 0.50). Long-term reoperation was required in three VUAS patients, showing a statistically significant difference between the groups (p = 0.05). CONCLUSION: Robotic YV plasty is feasible for both VUAS and BNC. While functional outcomes and stricture-free survival may be similar for both conditions, the perioperative outcomes were less favorable for VUAS patients.

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.

Updated systematic review and network meta-analysis of first-line treatments for metastatic renal cell carcinoma with extended follow-up data.

Immune checkpoint inhibitor (ICI)-based combination therapies are the recommended first-line treatment for metastatic renal cell carcinoma (mRCC). However, no head-to-head phase-3 randomized controlled trials (RCTs) have compared the efficacy of different ICI-based combination therapies. Here, we compared the efficacy of various first-line ICI-based combination therapies in patients with mRCC using updated survival data from phase-3 RCTs. Three databases were searched in June 2023 for RCTs that analyzed oncologic outcomes in mRCC patients treated with ICI-based combination therapies as first-line treatment. A network meta-analysis compared outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and complete response (CR) rate. Subgroup analyses were based on the International mRCC Database Consortium risk classification. The treatment ranking analysis of the entire cohort showed that nivolumab + cabozantinib (81%) had the highest likelihood of improving OS, followed by nivolumab + ipilimumab (75%); pembrolizumab + lenvatinib had the highest likelihood of improving PFS (99%), ORR (97%), and CR (86%). These results remained valid even when the analysis was limited to patients with intermediate/poor risk, except that nivolumab + ipilimumab had the highest likelihood of achieving CR (100%). Further, OS benefits of ICI doublets were not inferior to those of ICI + tyrosine kinase inhibitor combinations. Recommendation of combination therapies with ICIs and/or tyrosine kinase inhibitors based on survival benefits and patient pretreatment risk classification will help advance personalized medicine for mRCC.

Prognostic Significance of Grade Discrepancy Between Primary Tumor and Venous Thrombus in Nonmetastatic Clear-cell Renal Cell Carcinoma: Analysis of the REMEMBER Registry and Implications for Adjuvant Therapy.

BACKGROUND: Further stratification of the risk of recurrence of clear-cell renal cell carcinoma (ccRCC) with venous tumor thrombus (VTT) will facilitate selection of candidates for adjuvant therapy. OBJECTIVE: To assess the impact of tumor grade discrepancy (GD) between the primary tumor (PT) and VTT in nonmetastatic ccRCC on disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS). DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective analysis of a multi-institutional nationwide data set for patients with pT3N0M0 ccRCC who underwent radical nephrectomy and thrombectomy. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS: Pathology slides were centrally reviewed. GD, a bidirectional variable (upgrading or downgrading), was numerically defined as the VTT grade minus the PT grade. Multivariable models were built to predict DFS, OS, and CSS. RESULTS AND LIMITATIONS: We analyzed data for 604 patients with median follow-up of 42 mo (excluding events). Tumor GD between VTT and PT was observed for 47% (285/604) of the patients and was an independent risk factor with incremental value in predicting the outcomes of interest (all p < 0.05). Incorporation of tumor GD significantly improved the performance of the ECOG-ACRIN 2805 (ASSURE) model. A GD-based model (PT grade, GD, pT stage, PT sarcomatoid features, fat invasion, and VTT consistency) had a c index of 0.72 for DFS. The hazard ratios were 8.0 for GD = +2 (p < 0.001), 1.9 for GD = +1 (p < 0.001), 0.57 for GD = -1 (p = 0.001), and 0.22 for GD = -2 (p = 0.003) versus GD = 0 as the reference. According to model-converted risk scores, DFS, OS, and CSS significantly differed between subgroups with low, intermediate, and high risk (all p < 0.001). CONCLUSIONS: Routine reporting of VTT upgrading or downgrading in relation to the PT and use of our GD-based nomograms can facilitate more informed treatment decisions by tailoring strategies to an individual patient's risk of progression. PATIENT SUMMARY: We developed a tool to improve patient counseling and guide decision-making on other therapies in addition to surgery for patients with the clear-cell type of kidney cancer and tumor invasion of a vein.

Clinical Application of Digital and Computational Pathology in Renal Cell Carcinoma: A Systematic Review.

CONTEXT: Computational pathology is a new interdisciplinary field that combines traditional pathology with modern technologies such as digital imaging and machine learning to better understand the diagnosis, prognosis, and natural history of many diseases. OBJECTIVE: To provide an overview of digital and computational pathology and its current and potential applications in renal cell carcinoma (RCC). EVIDENCE ACQUISITION: A systematic review of the English-language literature was conducted using the PubMed, Web of Science, and Scopus databases in December 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO ID: CRD42023389282). Risk of bias was assessed according to the Prediction Model Study Risk of Bias Assessment Tool. EVIDENCE SYNTHESIS: In total, 20 articles were included in the review. All the studies used a retrospective design, and all digital pathology techniques were implemented retrospectively. The studies were classified according to their primary objective: detection, tumor characterization, and patient outcome. Regarding the transition to clinical practice, several studies showed promising potential. However, none presented a comprehensive assessment of clinical utility and implementation. Notably, there was substantial heterogeneity for both the strategies used for model building and the performance metrics reported. CONCLUSIONS: This review highlights the vast potential of digital and computational pathology for the detection, classification, and assessment of oncological outcomes in RCC. Preliminary work in this field has yielded promising results. However, these models have not yet reached a stage where they can be integrated into routine clinical practice. PATIENT SUMMARY: Computational pathology combines traditional pathology and technologies such as digital imaging and artificial intelligence to improve diagnosis of disease and identify prognostic factors and new biomarkers. The number of studies exploring its potential in kidney cancer is rapidly increasing. However, despite the surge in research activity, computational pathology is not yet ready for widespread routine use.

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.

Deep Learning Methodologies Applied to Digital Pathology in Prostate Cancer: A Systematic Review.

Deep learning (DL), often called artificial intelligence (AI), has been increasingly used in Pathology thanks to the use of scanners to digitize slides which allow us to visualize them on monitors and process them with AI algorithms. Many articles have focused on DL applied to prostate cancer (PCa). This systematic review explains the DL applications and their performances for PCa in digital pathology. Article research was performed using PubMed and Embase to collect relevant articles. A Risk of Bias (RoB) was assessed with an adaptation of the QUADAS-2 tool. Out of the 77 included studies, eight focused on pre-processing tasks such as quality assessment or staining normalization. Most articles (n = 53) focused on diagnosis tasks like cancer detection or Gleason grading. Fifteen articles focused on prediction tasks, such as recurrence prediction or genomic correlations. Best performances were reached for cancer detection with an Area Under the Curve (AUC) up to 0.99 with algorithms already available for routine diagnosis. A few biases outlined by the RoB analysis are often found in these articles, such as the lack of external validation. This review was registered on PROSPERO under CRD42023418661.

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).

Nephrectomy for kidney tumour increases the risk of de novo arterial hypertension.

OBJECTIVE: To evaluate prospectively the effects of surgical excision of renal tumours on blood pressure (BP). PATIENTS AND METHODS: In a multicentre prospective study, we evaluated 200 patients who underwent nephrectomy for renal tumour between 2018 and 2020 at seven departments of the French Network for Kidney Cancer, the UroCCR. All patients had localized cancer without pre-existing hypertension (HTN). Blood pressure was measured the week before nephrectomy, and at 1 month and 6 months after nephrectomy, according to the recommendations for home BP monitoring. Plasma renin was measured 1 week before surgery and 6 months after surgery. The primary endpoint was the occurrence of de novo HTN. The secondary endpoint was clinically significant increase in BP at 6 months, defined by an increase in systolic and/or diastolic ambulatory BP ≥10 mmHg or requirement for medical antihypertensive treatment. RESULTS: Blood pressure and renin measurements were available for 182 (91%) and 136 patients (68%), respectively. We excluded from the analysis 18 patients who had undeclared HTN detected on preoperative measurements. At 6 months, 31 patients (19.2%) had de novo HTN and 43 patients (26.3%) had a significant increase in their BP. Type of surgery was not associated with an increased risk of HTN (21.7% partial nephrectomy [PN] vs 15.7% radical nephrectomy [RN]; P = 0.59). There was no difference between plasmatic renin levels before and after surgery (18.5 vs 16; P = 0.46). In multivariable analysis, age (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.02-1.12; P = 0.03) and body mass index (OR 1.14, 95% CI 1.03-1.26; P = 0.01) were the only predictors of de novo HTN. CONCLUSION: Surgical treatment of renal tumours is associated with significant changes in BP, with de novo HTN occurring in almost 20% of the patients. These changes are not impacted by the type of surgery (PN vs RN). Patients who are scheduled to undergo kidney cancer surgery should be informed of these findings and have their BP closely monitored after the operation.

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.

Google searches for stress urinary incontinence treatment options: a worldwide trend analysis in the synthetic mesh controversy era.

PURPOSE: To analyze trends in worldwide public interest in the treatment options for stress urinary incontinence around the latest FDA 2019 ban on vaginal mesh for prolapse. METHODS: We used the web-based tool Google Trends to analyse online searches related to the following terms: 'pelvic floor muscle exercises', 'continence pessary', 'pubovaginal slings', 'Burch colposuspension', 'midurethral slings', 'injectable bulking agents'. Data were expressed as relative search volume on a scale of 0-100. Comparisons of annual relative search volume and average annual percentage change, were analyzed to assess loss or gain of interest. Finally, we assessed the impact of the last FDA alert. RESULTS: The mean annual relative search volume for midurethral slings was 20% in 2006 and significantly decreased until 8% in 2022 (p < 0.01). A regular decrease interest was recorded for autologous surgeries but a regain of interest for pubovaginal slings was registered since 2020 (+ 2.8%; p < 0.01). Conversely, a steep interest was noted for injectable bulking agents (average annual percentage change: + 4.4%; p < 0.01) and conservative therapies (p < 0.01). When trends were compared before and after the FDA 2019 alert, a lower research volume was found for midurethral slings, while a higher research volume was observed all others treatments (all p < 0.05). CONCLUSION: The online public researches about midurethral slings have considerably decreased following warnings on the use of transvaginal mesh. There seems to be a growing interest in conservative measures, bulking agents, and recently pubovaginal slings.

The IRON Study: Investigation of Robot-assisted Versus Open Nephron-sparing Surgery.

Background: Current literature does not provide large-scale data regarding clinical outcomes of robot-assisted (RAPN) versus open (OPN) partial nephrectomy. Moreover, data assessing predictors of long-term oncologic outcomes after RAPN are scarce. Objective: To compare perioperative, functional, and oncologic outcomes of RAPN versus OPN, and to investigate the predictors of oncologic outcomes after RAPN. Design setting and participants: This study included 3467 patients treated with OPN (n = 1063) or RAPN (n = 2404) for a single cT1-2N0M0 renal mass from 2004 to 2018 at nine high-volume European, North American, and Asian institutions. Outcome measurements and statistical analysis: The study outcomes were short-term postoperative, functional, and oncologic outcomes. Regression models investigated the effect of surgical approach (open vs Robot assisted) on study outcomes, and interaction tests were used for subgroup analyses. Propensity score matching for demographic and tumor characteristics was used in sensitivity analyses. Multivariable Cox-regression analyses identified predictors of oncologic outcomes after RAPN. Results and limitations: Baseline characteristics were similar between patients receiving RAPN and OPN, with only few differences. After adjusting for confounding, RAPN was associated with lower odds of intraoperative (odds ratio [OR]: 0.39, 95% confidence interval [CI]: 0.22, 0.68) and Clavien-Dindo ≥2 postoperative (OR: 0.29, 95% CI: 0.16, 0.50) complications (both p < 0.05). This association was not affected by comorbidities, tumor dimension, PADUA score, or preoperative renal function (all p > 0.05 on interaction tests). On multivariable analyses, we found no differences between the two techniques with respect to functional and oncologic outcomes (all p > 0.05). Overall, there were 63 and 92 local recurrences and systemic progressions, respectively, with a median follow-up after surgery of 32 mo (interquartile range: 18, 60). Among patients receiving RAPN, we assessed predictors of local recurrence and systemic progression with discrimination accuracy (ie, C-index) that ranged from 0.73 to 0.81. Conclusions: While cancer control and long-term renal function did not differ between RAPN and OPN, we found that the intra- and postoperative morbidity-especially in terms of complications-was lower after RAPN than after OPN. Our predictive models allow surgeons to estimate the risk of adverse oncologic outcomes after RAPN, with relevant implications for preoperative counseling and follow-up after surgery. Patient summary: In this comparative study on robotic versus open partial nephrectomy, functional and oncologic outcomes were similar between the two techniques, with lower morbidity-especially in terms of complications-for robot-assisted surgery. The assessment of prognosticators for patients receiving robot-assisted partial nephrectomy may help in preoperative counseling and provides relevant data to tailor postoperative follow-up.

Single-cell Deconvolution of a Specific Malignant Cell Population as a Poor Prognostic Biomarker in Low-risk Clear Cell Renal Cell Carcinoma Patients.

BACKGROUND: Intratumor heterogeneity (ITH) is a key feature in clear cell renal cell carcinomas (ccRCCs) that impacts outcomes such as aggressiveness, response to treatments, or recurrence. In particular, it may explain tumor relapse after surgery in clinically low-risk patients who did not benefit from adjuvant therapy. Recently, single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool to unravel expression ITH (eITH) and might enable better assessment of clinical outcomes in ccRCC. OBJECTIVE: To explore eITH in ccRCC with a focus on malignant cells (MCs) and assess its relevance to improve prognosis for low-risk patients. DESIGN, SETTING, AND PARTICIPANTS: We performed scRNA-seq on tumor samples from five untreated ccRCC patients ranging from pT1a to pT3b. Data were complemented with a published dataset composed of pairs of matched normal and ccRCC samples. INTERVENTION: Radical or partial nephrectomy on untreated ccRCC patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Viability and cell type proportions were determined by flow cytometry. Following scRNA-seq, a functional analysis was performed and tumor progression trajectories were inferred. A deconvolution approach was applied on an external cohort, and Kaplan-Meier survival curves were estimated with respect to the prevalence of malignant clusters. RESULTS AND LIMITATIONS: We analyzed 54 812 cells and identified 35 cell subpopulations. The eITH analysis revealed that each tumor contained various degrees of clonal diversity. The transcriptomic signatures of MCs in one particularly heterogeneous sample were used to design a deconvolution-based strategy that allowed the risk stratification of 310 low-risk ccRCC patients. CONCLUSIONS: We described eITH in ccRCCs, and used this information to establish significant cell population-based prognostic signatures and better discriminate ccRCC patients. This approach has the potential to improve the stratification of clinically low-risk patients and their therapeutic management. PATIENT SUMMARY: We sequenced the RNA content of individual cell subpopulations composed of clear cell renal cell carcinomas and identified specific malignant cells the genetic information of which can be used to predict tumor progression.

[Secondary tumors localized in testis]. / Localisations tumorales secondaires testiculaires.

Testis tumors are uncommon in oncology, and testicular metastasis from distant solid tumors are even rarer. We present two cases encountered in our department of pathology in CHU de Rennes, France. Moreover, we collected all reported cases in the Medline/PubMed databases of non-hematopoietic secondary testis tumors in adults, excluding autopsy studies, to propose an integrative study on this topic. In total, we report 98 cases of secondary testis lesions to prostate (n=38, 38.77 %), colorectal (n=19, 19.39%), gastric (n=12, 12.24%), kidney (n=7, 7.14%), lung (n=6, 6.12%) and other primary cancers. The median age at diagnosis was 66.5 years. We identified significantly more prostate adenocarcinoma (P<0.0001) when the primary tumor was known and significantly more colorectal adenocarcinoma (P=0.035) and pancreatic adenocarcinoma (P=0.002) when the primary tumor was unknown. The age at diagnosis was older when the primary tumor was known (P=0.007). We present the challenges for the diagnosis and propose some elements for diagnosis orientation. Finally, we discuss the possible ways of metastatic dissemination from primary site to testis, as illustrated by the two cases we present.

Machine-learning approach for prediction of pT3a upstaging and outcomes of localized renal cell carcinoma (UroCCR-15).

OBJECTIVES: To assess the impact of pathological upstaging from clinically localized to locally advanced pT3a on survival in patients with renal cell carcinoma (RCC), as well as the oncological safety of various surgical approaches in this setting, and to develop a machine-learning-based, contemporary, clinically relevant model for individual preoperative prediction of pT3a upstaging. MATERIALS AND METHODS: Clinical data from patients treated with either partial nephrectomy (PN) or radical nephrectomy (RN) for cT1/cT2a RCC from 2000 to 2019, included in the French multi-institutional kidney cancer database UroCCR, were retrospectively analysed. Seven machine-learning algorithms were applied to the cohort after a training/testing split to develop a predictive model for upstaging to pT3a. Survival curves for disease-free survival (DFS) and overall survival (OS) rates were compared between PN and RN after G-computation for pT3a tumours. RESULTS: A total of 4395 patients were included, among whom 667 patients (15%, 337 PN and 330 RN) had a pT3a-upstaged RCC. The UroCCR-15 predictive model presented an area under the receiver-operating characteristic curve of 0.77. Survival analysis after adjustment for confounders showed no difference in DFS or OS for PN vs RN in pT3a tumours (DFS: hazard ratio [HR] 1.08, P = 0.7; OS: HR 1.03, P > 0.9). CONCLUSIONS: Our study shows that machine-learning technology can play a useful role in the evaluation and prognosis of upstaged RCC. In the context of incidental upstaging, PN does not compromise oncological outcomes, even for large tumour sizes.