Robot-assisted Partial Nephrectomy for Hilar and Nonhilar Renal Masses: Comparison of Perioperative, Oncological, and Functional Results in a Multicentre Prospective Cohort (NEPRAH Study, UroCCR 175).

BACKGROUND AND OBJECTIVE: A hilar location for a renal tumour is sometimes viewed as a limiting factor for safe partial nephrectomy. Our aim was to evaluate perioperative, oncological, and functional outcomes of robot-assisted partial nephrectomy (RAPN) for hilar tumours (RAPN-H) in comparison to RAPN for nonhilar tumours (RAPN-NH). METHODS: We conducted an observational, multicentre cohort study using prospectively collected data from the French Research Network on Kidney Cancer (UroCCR). The registry includes data for 3551 patients who underwent RAPN for localised or locally advanced renal masses between 2010 and 2023 in 29 hospitals in France. We studied the impact of a hilar location on surgery, postoperative renal function, tumour characteristics, and survival. We also compared rates of trifecta achievement (warm ischaemia time [WIT] <25 min, negative surgical margins, and no perioperative complications) between the groups. Finally, we performed a subgroup analysis of RAPN without vascular clamping. Variables were compared in univariable analysis and using multivariable linear, logistic, and Cox proportional-hazards models adjusted for relevant patient and tumour covariates. KEY FINDINGS AND LIMITATIONS: The analytical population included 3451 patients, of whom 2773 underwent RAPN-NH and 678 underwent RAPN-H. Longer WIT (ß = 2.4 min; p < 0.01), longer operative time (ß = 11.4 min; p < 0.01) and a higher risk of postoperative complications (odds ratio 1.33; p = 0.05) were observed in the hilar group. Blood loss, the perioperative transfusion rate, postoperative changes in the estimated glomerular filtration rate, and trifecta achievement rates were comparable between the groups (p > 0.05). At mean follow-up of 31.9 mo, there was no significant difference in recurrence-free survival (hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.58-1.2; p = 0.3), cancer-specific survival (HR 1.1, 95% CI 0.48-2.6; p = 0.79), or overall survival (HR 0.89, 95% CI 0.52-1.53; p = 0.69). CONCLUSIONS AND CLINICAL IMPLICATIONS: Patient and tumour characteristics rather than just hilar location should be the main determinants of the optimal surgical strategy for hilar tumours. PATIENT SUMMARY: We found that kidney tumours located close to major kidney blood vessels led to a longer operation and a higher risk of complications during robot-assisted surgery to remove the tumour. However, tumours in these locations were not related to a higher risk of kidney function loss, cancer recurrence, or death.

Outcomes after radical nephrectomy with vena cava thrombectomy using multidisciplinary approach: A single center experience.

INTRODUCTION: To describe the perioperative outcomes in patients treated with radical nephrectomy with cava thrombectomy at all thrombi levels using a multidisciplinary approach, with or without extracorporeal circulation (ECC), and to identify factors associated with perioperative morbidity. METHODS: We retrospectively identified 42 patients who were diagnosed with renal cell carcinoma (RCC) and a vena cava thrombus and treated with radical nephrectomy and cava thrombectomy by a double surgical team at Lyon University Hospital from 2008 through 2021. The surgeons operated in the cardiothoracic operating theater to proceed with median sternotomy or ECC, if necessary. The primary endpoint of this study was perioperative morbidity and mortality assessed using the Clavien-Dindo scale. Complications were recorded until 90 days after surgery, and those classified as grade IIIa or higher were considered high-grade complications. RESULTS: Overall, 32 (76%) patients required ECC. No intraoperative mortality occurred; however, two patients (5%) died within 30 days. Complications occurred within 30 days in 30 patients (72%), with severe complications observed in 10 patients (24%). No further complications occurred between 30 and 90 days. Multivariate analysis revealed that age, thrombus level, ECC, American Society of Anesthesiologists physical status, symptoms, and metastasis at presentation were not significantly associated with high-grade complications (P>0.05). CONCLUSIONS: Multidisciplinary approach is essential and frequent use of ECC, when achieved by a trained team, may facilitate surgery, and is associated with low perioperative morbidity, especially for patients with high-level thrombi. LEVEL OF EVIDENCE: IV.

Renal and major clinical outcomes and their determinants after nephrectomy in patients with pre-existing chronic kidney disease: A retrospective cohort study.

The consequences of partial nephrectomy (PN) compared to radical nephrectomy (RN) are less documented in patients with pre-existing chronic kidney disease (CKD) or with solitary kidney (SK). We assessed renal outcomes, and their determinants, after PN or RN in a retrospective cohort of patients with moderate-to-severe CKD (RN-CKD and PN-CKD) or SK (PN-SK). All surgical procedures conducted between 2013 and 2018 in our institution in patients with pre-operative estimated glomerular filtration rate (eGFR)<60 mL/min/1.73m2 or with SK were included. The primary outcome was a composite criterion including CKD progression or major adverse cardio-vascular events (MACE) or death, assessed one year after surgery. Predictors of the primary outcome were determined using multivariate analyses. A total of 173 procedures were included (67 RN, and 106 PN including 27 SK patients). Patients undergoing RN were older, with larger tumors. Preoperative eGFR was not significantly different between the groups. One year after surgery, PN-CKD was associated with lower rate of the primary outcome compared to RN-CKD (43% vs 71% p = 0.007). In multivariate analysis, independent risk factors for the primary outcome were postoperative AKI (stage 1 to stage 3 ranging from OR = 8.68, 95% CI 3.23-23.33, to OR = 28.87, 95% CI 4.77-167.61), larger tumor size (OR = 1.21 per cm, 95% CI 1.02-1.45), while preoperative eGFR, age, sex, diabetes mellitus, and hypertension were not. Postoperative AKI after PN or RN was the major independent determinant of worse outcomes (CKD progression, MACE, or death) one year after surgery.

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.

Stereotactic body radiotherapy for inoperable patients with renal carcinoma.

INTRODUCTION: The objective of this study was to analyze the dose-dependent safety profiles of stereotactic body radiation therapy (SBRT) in patients with inoperable small renal cell carcinoma (RCC). MATERIAL: This is a retrospective study from a single institution including patients with RCC treated between 2011 and 2020 with SBRT on the primary tumor or on a local recurrence after surgery. All patients had been declared inoperable or refused surgery. The patients were divided into two dose level groups: group 1 (BED10<60Gy) and group 2 (BED10≥60Gy). Acute and late toxicities, renal function and local control (LC) were compared between the two groups. RESULTS: A total of 24 patients were analyzed with an average follow-up of 25.1 months. Nine patients (37%) and three patients (14%) reported grade 1-2 acute and late toxicities, respectively. No grade≥3 acute and late toxicities were observed. There was no significant difference in acute and late toxicities between the two groups (P=0.21 and P=0.27, respectively). There was no significant difference in estimated glomerular filtration rate in the 15 patients, eligible for renal toxicity analysis between the pre-radiation and the 12-month follow-up (P=0.1) and the last follow-up (P=0.06). LC at the last follow-up was noted in 19 out of 23 patients (83%) and was based on imaging acquisition. LC was 77.8% for group 1 and 85.7% for group 2 (P=1.95). CONCLUSION: Dose escalation was not associated with an increase in acute and late grade≥2 toxicities. There appears to be a trend towards increased LC at higher doses.

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.

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.

Bilateral Pedicled Scrotal Flaps as an Alternative to Skin Graft in Penile Shaft Defects Repair.

OBJECTIVE: To analyze surgical and functional outcomes of bilateral pedicled scrotal flaps for penile shaft reconstruction. MATERIALS AND METHODS: A retrospective analysis was performed on 22 patients who underwent penile shaft reconstruction with bilateral pedicled scrotal flaps between 2009 and 2017. Demographics, peri-operative data, and surgical complications were collected. Functional outcomes were analyzed using a questionnaire made of the erection hardness score, the patient and observer scar assessment scale, and a 10-point Likert scale measuring patients... satisfaction about their skin coloration, sensitivity, elasticity and thickness, penile size, scrotal volume, erection quality, penetration ability, pain, sexual satisfaction, body image, masculinity, self-esteem, and global satisfaction. RESULTS: Patients exhibited a wide range of indications, including buried penis (27.2%), or subcutaneous injections of foreign material (27.2%). Early complications were suture dehiscence (31.8%), infection (13.6%) and hematoma (4.6%), associated with 9.1% of surgical revisions. Late complications were skin retraction (27.3%), testicular ascension (22.7%), pyramidal shape (4.6%) or shortening (13.6%) of the penis, associated with 27.3% of surgical revisions. For the 12 patients who answered the questionnaire, median erection hardness score and patient and observer scar assessment scale score [IQR] were 3.5 out of 4 [2.5-4] and 11.5 out of 60 [9.5-22], respectively. The patients reported a positive impact of the surgery on their psychological condition, with a median score of global satisfaction of 8 [IQR 7.5-9.5]. CONCLUSION: Bilateral pedicled scrotal flaps seem.ßto be a safe alternative for shaft defects reconstruction despite a potential need of surgical revision, providing satisfactory functional outcomes.

A multicenter comparative matched-pair analysis of percutaneous tumor ablation and robotic-assisted partial nephrectomy of T1b renal cell carcinoma (AblatT1b study-UroCCR 80).

OBJECTIVE: Renal cell carcinomas represent the sixth- and tenth-most frequently diagnosed cancer in men and women. Recently, percutaneous-guided thermal ablations have proved to be as effective as partial nephrectomy and safer for treating small renal masses (i.e., < 3 cm). This study compared the perioperative and recurrence outcomes of percutaneous thermal ablation (TA) and robotic-assisted partial nephrectomy (RAPN) for the treatment of T1b renal cell carcinomas (4.1-7 cm). METHODS: Retrospective data from 11 centers on the national database, between 2010 and 2020, included 81 patients treated with thermal ablation (TA) and 308 patients treated with RAPN for T1b renal cell carcinoma, collected retrospectively and matched for tumor size, histology results, and the RENAL score. TA included cryoablation and microwave ablation. Endpoints compared the rate between the two groups: local recurrence, metastases, complications, renal function decrease, and length of hospitalization. RESULTS: After matching, 75 patients were included in each group; mean age was 76.6 (± 9) in the TA group and 61.1 (± 12) in the RAPN group, including 69.3% and 76% men respectively. The local recurrence (LR) rate was significantly higher in the TA group than in the PN group (14.6% vs 4%; p = 0.02). The LR rate was 20% (1/5) after microwave ablation, 11.1% (1/9) after radiofrequency ablation, and 14.7% (9/61) after cryoablation. The major complication rate (Clavien-Dindo ≥ 3) was higher following PN than after TA (5.3% vs 0%; p < 0.001). Metastases, eGFR decrease, and length of hospitalization did not differ significantly between the two groups. CONCLUSIONS: The local recurrence rate was significantly higher after thermal ablation; however, thermal ablation resulted in significantly lower rates of complications. Thermal ablation and robotic-assisted partial nephrectomy are effective treatments for T1b renal cancer; however, the local recurrence rate was higher after thermal ablation. KEY POINTS: • The local recurrence rate was significantly higher in the thermal ablation group than in the partial nephrectomy group. • The major complication rate (Clavien-Dindo ≥ 3) was higher following PN than after TA (5.3% vs. 0%; p < 0.001).

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.

Safety and Efficacy of Stereotactic Ablative Radiation Therapy for Renal Cell Cancer: 24-Month Results of the RSR1 Phase 1 Dose Escalation Study.

PURPOSE: Stereotactic body radiation therapy (SBRT) has become a new therapeutic option for primary renal cell carcinoma. However, treatment doses lack consistency in the literature. The primary objective of this study was to determine the maximum tolerated dose for renal cancer SBRT. METHODS AND MATERIALS: This phase 1 multicentric dose-escalation study assessed 4 dose levels: 8 Gy × 4, 8 Gy × 5, 10 Gy × 4, and 12 Gy × 4. The primary objective of this study was to determine the maximal tolerated dose, defined by the occurrence of dose-limiting toxicity was defined as any acute side effect of grade ≥4 based on the Common Terminology Criteria for Averse Events, version 4.0. RESULTS: From October 2010 to September 2017, 13 patients were enrolled. The median follow-up was 23 months. There was no dose-limiting toxicity in our study, and the highest dose was reached successfully. No acute or late toxic effects above grade 2 were seen. There was no significant alteration of renal function after treatment. At 24 months, 2 patients had partial response and the others had stable disease. CONCLUSIONS: After 24 months of follow-up, no dose-limiting toxicity was seen at any of the prescribed dose levels in our study. The findings suggest that our last dose level of 48 Gy in 4 12-Gy fractions can be considered safe and can be used in further studies.

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.

Determining the outcomes of urethral construction in phalloplasty.

OBJECTIVE: To evaluate the surgical and functional outcomes of urethral reconstruction associated with phalloplasty, depending on the surgical techniques and patient history. MATERIALS AND METHODS: We conducted a single-centre retrospective study including 89 patients who underwent phalloplasty with urethral reconstruction between 2007 and 2018. Patients included were trans-male patients undergoing gender-affirming surgery and cis-male patients undergoing penile reconstruction after trauma, congenital malformation, or cancer. Urethral reconstructions were performed by free flap or skin graft (total or thin). Secondary urethroplasty may include direct vision urethrotomy, excision-anastomosis, or augmentation urethroplasty (skin graft, buccal mucosa graft). Patient demographics, medical history, peri- and postoperative data were collected from patient files. Functional results were evaluated using individual questionnaires. RESULTS: The mean (±sd) follow-up duration was 5.5 (±3.7) years. No significant difference was found for total urethral complication rate (fistula and/or stricture) according to type of urethral construction (70.9% for free flap urethra vs 73.5% for skin graft urethra; P = 0.911), nor according to the patient's grounds for surgery (72.7% for cis-male vs 71.8% for trans-male patients; P = 1). A total of 36 patients (40.5%) answered the functional questionnaire, of whom 80.5% reported usually voiding while standing and 47.5% were comfortable with urinating in public. CONCLUSIONS: Urethral construction in phalloplasty is associated with a high complication and revision rate regardless of the type of urethral reconstruction. Voiding in a standing position is generally possible but should not conceal feeble functional results.

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.

Rectourethral Fistula Induced by Localised Prostate Cancer Treatment: Surgical and Functional Outcomes of Transperineal Repair with Gracilis Muscle Flap Interposition.

BACKGROUND: Transperineal repair of rectourethral fistula (RUF) following prostate cancer treatment with gracilis muscle flap interposition (GMFI) leads to favourable outcomes, but published data are still lacking, notably concerning functional aspects. OBJECTIVE: To assess surgical and functional outcomes of this treatment of RUF. DESIGN, SETTING, AND PARTICIPANTS: A retrospective study was conducted in two referral hospitals including 21 patients who underwent RUF transperineal repair with GMFI between 2008 and 2020. SURGICAL PROCEDURE: The standard vertical perineal approach is performed for fistula dissection. Bladder and rectal defects are closed separately. After dissection from its facia, the flap is harvested, preserving its pedicle; it is brought to the perineum and placed between the urethra and the rectum to fully cover the sutures. MEASUREMENTS: Fistula closure (clinical data and postoperative cystography), digestive stoma closure, and complications graded according to the Clavien-Dindo classification were reviewed. Functional results were assessed using the Urinary Symptom Profile (USP) questionnaire, anal incontinence St Mark's score, Patient Observer Scar Assessment Scale (POSAS) score, and a nonvalidated Likert scale questionnaire assessing issues with lower extremity functionality. RESULTS AND LIMITATIONS: The median (interquartile range) follow-up was 27 (8-47) mo. Fistula closure was successful for 20 patients (95% success). Digestive stoma was closed in 10/12 shunted patients (83%). Two (9%) Clavien-Dindo grade ≥3b complications were reported (one urinoma in a kidney transplant patient and one thigh haematoma evacuation). Eighteen patients (86%) completed the postoperative questionnaire; 11/18 (61%) had significant urinary incontinence. The mean (standard deviation) USP dysuria score was 1/9 (1.2), mean St Mark's score was 5/24 (5), mean POSAS score was 19/70 (11), mean lower extremity functionality score was 2/20 (4), and mean procedure patient satisfaction score was 9/10 (2). The retrospective design and limited number of patients are the main limitations. CONCLUSIONS: The present study found an excellent success rate and low morbidity for RUF transperineal repair with GMFI. Functional outcomes were satisfactory despite a high urinary incontinence rate. PATIENT SUMMARY: We performed an analysis of the outcomes of perineal approach surgery with muscle interposition for closing abnormal communication between the bladder and the rectum after prostate cancer treatment. This surgical technique was found to be safe to perform and provides a high success rate, with patients being satisfied despite poor urinary continence outcomes.

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.