Preparing for the Worst: Management and Predictive Factors of Open Conversion During Minimally Invasive Renal Tumor Surgery (UroCCR-135 Study).

Background and objective: Data regarding open conversion (OC) during minimally invasive surgery (MIS) for renal tumors are reported from big databases, without precise description of the reason and management of OC. The objective of this study was to describe the rate, reasons, and perioperative outcomes of OC in a cohort of patients who underwent MIS for renal tumor initially. The secondary objective was to find the factors associated with OC. Methods: Between 2008 and 2022, of the 8566 patients included in the UroCCR project prospective database (NCT03293563), who underwent laparoscopic or robot-assisted minimally invasive partial (MIPN) or radical (MIRN) nephrectomy, 163 experienced OC. Each center was contacted to enlighten the context of OC: "emergency OC" implied an immediate life-threatening situation not reasonably manageable with MIS, otherwise "elective OC". To evaluate the predictive factors of OC, a 2:1 paired cohort on the UroCCR database was used. Key findings and limitations: The incidence rate of OC was 1.9% for all cases of MIS, 2.9% for MIRN, and 1.4% for MIPN. OC procedures were mostly elective (82.2%). The main reason for OC was a failure to progress due to anatomical difficulties (42.9%). Five patients (3.1%) died within 90 d after surgery. Increased body mass index (BMI; odds ratio [OR]: 1.05, 95% confidence interval [CI]: 1.01-1.09, p = 0.009) and cT stage (OR: 2.22, 95% CI: 1.24-4.25, p = 0.008) were independent predictive factors of OC. Conclusions and clinical implications: In MIS for renal tumors, OC was a rare event (1.9%), caused by various situations, leading to impaired perioperative outcomes. Emergency OC occurred once every 300 procedures. Increased BMI and cT stage were independent predictive factors of OC. Patient summary: The incidence rate of open conversion (OC) in minimally invasive surgery for renal tumors is low. Only 20% of OC procedures occur in case of emergency, and others are caused by various situations. Increased body mass index and cT stage were independent predictive factors of OC.

Congenital Haemostasis Disorders and Urology Surgery: Is It Safe?

BACKGROUND: There are no specific recommendations for the management of patients with bleeding disorders (BD), such as haemophilia A (HA), haemophilia B (HB), or von Willebrand disease (WD), in urology surgery. Methods: We conducted a retrospective study of 32 patients with HA, HB, or WD of any severity. Fifty-seven procedures were performed between January 2017 and September 2023. Surgical interventions were divided into two groups: those with and without electrocoagulation. The control patients were successively matched in a 2:1 ratio. Results: The study group consisted of 30 men and 2 women, with 23 HA, 2 HB, and 7 WD. The median age of the patients was 69 years. The BD group had a longer hospital stay of 4 days compared to 1 day (p < 0.0001). The incidence of bleeding events was 21% versus 2% (p < 0.0001), and the incidence of complications was 21% versus 7% (p = 0.0036) for Clavien 1-2 respectively. In the subgroup with intraoperative coagulation, the readmission rate at 30 days was higher (17% vs. 3%, p = 0.00386), as was the transfusion rate (17% vs. 3%, p = 0.0386). Conclusions: This study showed that urological procedures in patients with bleeding disorders were associated with a higher risk of bleeding and complications.

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.

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.

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.

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).

Urinary Continence Resolution after Bariatric Surgery: Long-Term Results after Six-Year Follow-Up.

BACKGROUND: Bariatric surgery is known to improve stress urinary incontinence (SUI) and overactive bladder disorders (OAB). However, there is little long-term follow-up in the literature. OBJECTIVE: To determine the long-term effect of bariatric procedures on SUI and OAB and their impact on quality of life, we applied the ICIQ and USP questionnaires. SETTING: The research was conducted at a French university hospital with expertise in bariatric surgery. METHODS: We performed an updated follow-up at 6 years of a prospective cohort of 83 women who underwent a bariatric procedure between September 2013 and September 2014. The women completed the USP and ICIQ questionnaires before surgery, 1 year and 6 years after the surgery. RESULTS: Of the 83 patients, 67 responded (80.7%) in full. SUI remained improved at 6 years: the USP score decreased from 3 [1; 7] before surgery to 0 [0; 1] (p = 0.0010) at 1 year after surgery and remained at 0 [0; 0] (p = 0.0253) at 6 years. The decrease in the OAB symptom score remained statistically significant: 3 [1; 7] before the surgery vs. 2 [0; 5] at 6 years (p = 0.0150). However, this improvement was significantly less pronounced than at 1 year: 0 [0; 1] (p = 0.002). CONCLUSIONS: Bariatric surgery seems to be effective at treating SUI and OAB with a long-lasting effects, still noted at 6 years.

Is CIS a Contraindication to Hyperthermic Intravesical Chemotherapy (HIVEC) after BCG-Failure?

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

Efficacy of hyperthermic intravesical chemotherapy (HIVEC) in patients with non-muscle invasive bladder cancer after BCG failure.

PURPOSE: To evaluate hyperthermic intravesical chemotherapy (HIVEC) efficacy regarding 1-year disease-free survival (RFS) rate and bladder preservation rate in patients with non-muscle invasive bladder cancer (NMIBC) who fail bacillus Calmette-Guérin (BCG) therapy. METHODS: This is a multicenter retrospective series from a national database (7 expert centers). Between January 2016 and October 2021, patients treated with HIVEC for NMIBC who failed BCG have been included in our study. These patients had a theoretical indication for cystectomy but were ineligible for surgery or refused it. RESULTS: A total of 116 patients treated with HIVEC and with a follow-up > 6 months were included in this study and retrospectively analyzed. The median follow-up was 20.6 months. The 12 month-RFS (recurrence-free survival) rate was 62.9%. The bladder preservation rate was 87.1%. Fifteen patients (12.9%) progressed to muscle infiltration, three of them having a metastatic disease at the time of progression. Predictive factors of progression were T1 stage, high grade and very high-risk tumors according to the EORTC classification. CONCLUSION: Chemohyperthermia using HIVEC achieved an RFS rate of 62.9% at 1 year and enabled a bladder preservation rate of 87.1%. However, the risk of progression to muscle-invasive disease is not negligible, particularly for patients with very high-risk tumors. In these patients who fail BCG, cystectomy should remain the standard of care and HIVEC may be discussed cautiously for patients who are not eligible for surgery and well informed of the risk of progression.

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.

Updated National Study of Functional Graft Renal Cell Carcinomas: Are They a Different Entity?

OBJECTIVE: To analyze de novo graft carcinoma characteristics from our updated national multicentric retrospective cohort. METHODS: Thirty-two transplant centers have retrospectively completed the database. This database concerns all kidney graft tumors including urothelial, and others type but excludes renal lymphomas over 31 years. RESULTS: One hundred and fifty twokidney graft carcinomas were diagnosed in functional grafts. Among them 130 tumors were Renal Cell Carcinomas. The calculated incidence was 0.18%. Median age of the allograft at diagnosis was 45.4 years old. The median time between transplantation and diagnosis was 147.1 months. 60 tumors were papillary carcinomas and 64 were clear cell carcinomas. Median tumor size was 25 mm. 18, 64, 21 and 1 tumors were respectively Fuhrman grade 1, 2, 3 and 4. Nephron sparing surgery (NSS) was performed on 68 (52.3%) recipients. Ablative therapy was performed in 23 cases (17.7%). Specific survival rate was 96.8%. CONCLUSION: This study confirmed that renal graft carcinomas are a different entity: with a younger age of diagnosis; a lower stage at diagnosis; a higher incidence of papillary subtypes.

Positive surgical margin's impact on short-term oncological prognosis after robot-assisted partial nephrectomy (MARGINS study: UroCCR no 96).

The oncological impact of positive surgical margins (PSM) after robot-assisted partial nephrectomy (RAPN) is still under debate. We compared PSM and Negative Surgical Margins (NSM) in terms of recurrence-free survival (RFS), metastasis-free survival (MFS) and overall survival (OS) after RAPN, and we identified predictive factors of PSM. Multi-institutional study using the UroCCR database, which prospectively included 2166 RAPN between April 2010 and February 2021 (CNIL DR 2013-206; NCT03293563). Two groups were retrospectively compared: PSM versus NSM. Prognostic factors were assessed using Kaplan-Meyer curves with log-Rank test, cox hazard proportional risk model and logistic regression after univariate comparison. 136 patients had PSM (6.3%) and 2030 (93.7%) had NSM. During a median follow-up of 19 (9-36) months after RAPN, 160 (7.4%) recurrences were reported. Kaplan-Meier curves and analysis suggested that RFS, MFS and OS were not affected by a PSM (p = 0.68; 0.71; 0.88, respectively). In multivariate analysis predictors of PSM were a lower RENAL score (p = 0.001), longer warm ischemia time (WIT) (p = 0.003) and Chromophobe Renal Cell Carcinoma (chrRCC) (p = 0.043). This study found no impact of PSM on RFS, MFS or OS, and predictors of PSM were the RENAL score, WIT and chrRCC.

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.

Nivolumab, nivolumab-ipilimumab, and VEGFR-tyrosine kinase inhibitors as first-line treatment for metastatic clear-cell renal cell carcinoma (BIONIKK): a biomarker-driven, open-label, non-comparative, randomised, phase 2 trial.

BACKGROUND: We previously reported a 35-gene expression classifier identifying four clear-cell renal cell carcinoma groups (ccrcc1 to ccrcc4) with different tumour microenvironments and sensitivities to sunitinib in metastatic clear-cell renal cell carcinoma. Efficacy profiles might differ with nivolumab and nivolumab-ipilimumab. We therefore aimed to evaluate treatment efficacy and tolerability of nivolumab, nivolumab-ipilimumab, and VEGFR-tyrosine kinase inhibitors (VEGFR-TKIs) in patients according to tumour molecular groups. METHODS: This biomarker-driven, open-label, non-comparative, randomised, phase 2 trial included patients from 15 university hospitals or expert cancer centres in France. Eligible patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status of 0-2, and had previously untreated metastatic clear-cell renal cell carcinoma. Patients were randomly assigned (1:1) using permuted blocks of varying sizes to receive either nivolumab or nivolumab-ipilimumab (ccrcc1 and ccrcc4 groups), or either a VEGFR-TKI or nivolumab-ipilimumab (ccrcc2 and ccrcc3 groups). Patients assigned to nivolumab-ipilimumab received intravenous nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses followed by intravenous nivolumab 240 mg every 2 weeks. Patients assigned to nivolumab received intravenous nivolumab 240 mg every 2 weeks. Patients assigned to VEGFR-TKIs received oral sunitinib (50 mg/day for 4 weeks every 6 weeks) or oral pazopanib (800 mg daily continuously). The primary endpoint was the objective response rate by investigator assessment per Response Evaluation Criteria in Solid Tumors version 1.1. The primary endpoint and safety were assessed in the population who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT02960906, and with the EU Clinical Trials Register, EudraCT 2016-003099-28, and is closed to enrolment. FINDINGS: Between June 28, 2017, and July 18, 2019, 303 patients were screened for eligibility, 202 of whom were randomly assigned to treatment (61 to nivolumab, 101 to nivolumab-ipilimumab, 40 to a VEGFR-TKI). In the nivolumab group, two patients were excluded due to a serious adverse event before the first study dose and one patient was excluded from analyses due to incorrect diagnosis. Median follow-up was 18·0 months (IQR 17·6-18·4). In the ccrcc1 group, objective responses were seen in 12 (29%; 95% CI 16-45) of 42 patients with nivolumab and 16 (39%; 24-55) of 41 patients with nivolumab-ipilimumab (odds ratio [OR] 0·63 [95% CI 0·25-1·56]). In the ccrcc4 group, objective responses were seen in seven (44%; 95% CI 20-70) of 16 patients with nivolumab and nine (50% 26-74) of 18 patients with nivolumab-ipilimumab (OR 0·78 [95% CI 0·20-3·01]). In the ccrcc2 group, objective responses were seen in 18 (50%; 95% CI 33-67) of 36 patients with a VEGFR-TKI and 19 (51%; 34-68) of 37 patients with nivolumab-ipilimumab (OR 0·95 [95% CI 0·38-2·37]). In the ccrcc3 group, no objective responses were seen in the four patients who received a VEGFR-TKI, and in one (20%; 95% CI 1-72) of five patients who received nivolumab-ipilimumab. The most common treatment-related grade 3-4 adverse events were hepatic failure and lipase increase (two [3%] of 58 for both) with nivolumab, lipase increase and hepatobiliary disorders (six [6%] of 101 for both) with nivolumab-ipilimumab, and hypertension (six [15%] of 40) with a VEGFR-TKI. Serious treatment-related adverse events occurred in two (3%) patients in the nivolumab group, 38 (38%) in the nivolumab-ipilimumab group, and ten (25%) patients in the VEGFR-TKI group. Three deaths were treatment-related: one due to fulminant hepatitis with nivolumab-ipilimumab, one death from heart failure with sunitinib, and one due to thrombotic microangiopathy with sunitinib. INTERPRETATION: We demonstrate the feasibility and positive effect of a prospective patient selection based on tumour molecular phenotype to choose the most efficacious treatment between nivolumab with or without ipilimumab and a VEGFR-TKI in the first-line treatment of metastatic clear-cell renal cell carcinoma. FUNDING: Bristol Myers Squibb, ARTIC.

Postoperative outcomes of elderly patients undergoing partial nephrectomy.

To describe clinical outcomes of patients aged 75 years and above after partial nephrectomy (PN), and to assess independent factors of postoperative complications. We retrospectively reviewed information from our multi-institutional database. Every patient over 75 years old who underwent a PN between 2003 and 2016 was included. Peri-operative and follow up data were collected. Multivariate logistic regression was performed to determine independent predictive factors of postoperative complications. We reviewed 191 procedures including 69 (40%) open-surgery, and 122 (60%) laparoscopic procedures, of which 105 were robot-assisted. Median follow-up was 25 months. The mean age was 78 [75-88]. The American Society of Anesthesiologist's score was 1, 2, 3 and 4 in 10.5%, 60%, 29% and 0.5% of patients respectively. The mean tumor size was 4.6 cm. Indication of PN was elective in 122 (65%) patients and imperative in 52 patients (28%). The median length of surgery was 150(± 60) minutes, and the median estimated blood loss 200 ml. The mean glomerular filtration rate was 71.5 ml/minute preoperatively, and 62 ml/min three months after surgery. The severe complications (Clavien III-V) rate was 6.2%. On multivariate analysis, the robotic-assisted procedure was an independent protective factor of medical postoperative complications (Odds Ration (OR) = 0.31 [0.12-0.80], p = 0.01). It was adjusted for age and RENAL score, robotic-assisted surgery (OR = 0.22 [0.06-0.79], p = 0.02), and tumor size (OR = 1.13 [1.02-1.26], p = 0.01), but the patients age did not forecast surgical complications. Partial nephrectomy can be performed safely in elderly patients with an acceptable morbidity, and should be considered as a viable treatment option. Robotic assistance is an independent protective factor of postoperative complications.

Over-diagnosed prostate cancer in solid organ recipients: lessons from the last 3 decades.

INTRODUCTION: Prostate cancer (PC) is the most common neoplasia in men. With aging of solid organ transplant recipients (SOTR), its incidence is likely to increase. The aim of this study was to analyze PC screening results retrospectively in renal transplant recipients (RTR), hepatic transplant recipients (HTR) and cardiac transplant recipients (CTR). PATIENTS AND METHODS: A retrospective monocentric study of PC diagnosed in renal, hepatic or cardiac transplanted patients since 1989 was performed. All the patients were followed annually by digital rectal examination and prostate serum antigen (PSA) dosage. RESULTS: 57 PC were diagnosed in 1565 SOTR male patients (3.6%): 35 RTR, 15 HTR, and 7 CTR. Standard incidence ratio (SIR) was 41.9. Mean age at the time of diagnosis was 64.5 (60.5-69.2). Mean time between transplantation and PC diagnosis was 95.7 (39.0-139.5) months. Median PSA rate was 7.0 (6.2-13) ng/mL. Clinical stages were T1, T2, and T3, respectively, for 29, 22 and 6 patients. Diagnosis was done by screening in 52 patients, after prostatitis in 1 and bone pain in another. Three PC were discovered on prostate chips after transurethral resection. Two patients were treated by active surveillance. 39 (68%) patients (25 RTR, 11 HTR and 3 CTR) were treated by radical prostatectomy. Histological results were 30 pT2 and 9 pT3 tumors, with 7 positive surgical margins. Gleason score was 5, 6, 7, 8 and 9 in, respectively, in 2, 24, 11, 1 and 1 patients. One patient with positive pelvic nodes was treated with hormonal therapy (HT). One had a biochemical relapse at 10 months and underwent salvage radiotherapy. Median follow-up was 85.2 months (46.1-115.0). 23 (40.4%) patients died. Two (3.6%) RTR and 1 (1.8%) CTR died from their PC. Standard incidence ratio were, respectively, 42.4, 48.2 and 39 in RTR, HTR and CTR. CONCLUSION: Systematic screening in male SOTR after 50 years old could not be recommended. In the last 3 decades, we diagnosed too many low-risk prostate cancers strongly increasing the SIR but failing to decrease prostate cancer related mortality. SOTR should undergo individual screening with prior MRI when PSA rates are high. Management should not be different from that of the general population.