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Objective: Renal Tumor biopsy (RTB) can assist clinicians in determining the most suitable approach for treatment of renal cancer. However, RTB's limitations in accurately determining histology and grading have hindered its broader adoption and data on the concordance rate between RTB results and final pathology after surgery are unavailable. Therefore, we aimed to develop a machine learning algorithm to optimize RTB technique and to investigate the degree of concordance between RTB and surgical pathology reports., Materials and Methods: Within a prospectively maintained database, patients with indeterminate renal masses who underwent RTB at a single tertiary center were identified. We recorded and analyzed the approach (US vs. CT), the number of biopsy cores (NoC), and total core tissue length (LoC) to evaluate their impact on diagnostic outcomes. The K-Nearest Neighbors (KNN), a non-parametric supervised machine learning model, predicted the probability of obtaining pathological characterization and grading. In surgical patients, final pathology reports were compared with RTB results., Results: Overall, 197 patients underwent RTB. Overall, 89.8% (n=177) and 44.7% (n=88) of biopsies were informative in terms of histology and grading, respectively. The discrepancy rate between the pathology results from renal tissue biopsy (RTB) and the final pathology report following surgery was 3.6% (n=7) for histology and 5.0% (n=10) for grading. According to the machine learning model, a minimum of 2 cores providing at least 0.8 cm of total tissue should be obtained to achieve the best accuracy in characterizing the cancer. Alternatively, in cases of RTB with more than two cores, no specific minimum tissue threshold is required., Conclusions: The discordance rates between RTB pathology and final surgical pathology are notably minimal. We defined an optimal renal biopsy strategy based on at least 2 cores and at least 0.8 cm of tissue or at least 3 cores and no minimum tissue threshold., Patients Summary: RTB is a useful test for kidney cancer, but it's not always perfect. Our study shows that it usually matches up well with what doctors find during surgery. Using machine learning can make RTB even better by helping doctors know how many samples to take. This helps doctors treat kidney cancer more accurately., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Objective: Metabolic syndrome (MetS) is a clinical condition associated with higher rates of overall and cardiovascular mortality. There is scarce evidence regarding the impact of MetS on surgical and functional outcomes for patients undergoing partial nephrectomy (PN) for clinically localized small renal masses (SRMs)., Methods: We analyzed data from a prospectively maintained institutional database for 690 patients with cT1a renal cancer undergoing PN between 2000 and 2023 at a tertiary referral center. MetS was defined according to international guidelines. Cumulative incidence curves were used to estimate the 5-yr risk of stage IIIB-V chronic kidney disease (CKD) stage and other-cause mortality (OCM). Multivariable regression models were used to analyze the impact of MetS on the risk of complications, acute kidney injury (AKI), stage IIIB-V CKD, and OCM., Key Findings and Limitations: Overall, 10% of the PN cohort had MetS. The MetS group was older (median age 70 yr, interquartile range [IQR] 65-74 vs 61 yr, IQR 50-69; p  < 0.001) and had worse preoperative kidney function (median estimated glomerular filtration rate 65 [IQR 62-81] vs 88 [IQR 69-98] ml/min/1.73 m 2 ; p  < 0.001) than the group without MetS. The MetS group had higher incidence of complications (odds ratio [OR] 1.81, 95% confidence interval [CI] 1.05-3.08; p  = 0.03) and postoperative AKI (OR 3.17, 95% CI 1.54-6.41; p  = 0.001). The 5-yr risk of stage IIIB-V CKD (45% vs 7.2%; hazard ratio [HR] 2.34, 95% CI 1.27-4.30; p  = 0.006) and OCM (14% vs 3.5%; HR 3.00, 95% CI 1.06-8.55; p  = 0.039) were also higher in the MetS group. The main limitations are the extended accrual time and unmeasured confounders that could potentially affect outcomes., Conclusions and Clinical Implications: Patients with MetS had worse postoperative, functional, and survival outcomes after SRM surgery in comparison to patients without MetS. Multidisciplinary care could help in reducing the preoperative metabolic burden in these patients. Further research should explore if alternative approaches (eg, surveillance or focal therapy) could minimize postoperative comorbidities and protect long-term renal function in this population., Patient Summary: Patients with a condition called metabolic syndrome who have part of their kidney removed for small kidney tumors are at higher risk of complications and long-term kidney issues. Patient care from a multidisciplinary team could help in reducing the metabolic burden before surgery. Further research is needed to explore if less invasive treatment options could reduce these risks., (© 2024 The Author(s).)

Purpose: In absence of predictive models, preoperative estimation of the probability of completing partial (PN) relative to radical nephrectomy (RN) is invariably inaccurate and subjective. We aimed to develop an evidence-based model to assess objectively the probability of PN completion based on patients' characteristics, tumor's complexity, urologist expertise and surgical approach., Design, Setting and Participants: 675 patients treated with PN or RN for cT 1-2 cN 0 cM 0 renal mass by seven surgeons at one single experienced centre from 2000 to 2019., Outcomes Measurements and Statistical Analyses: The outcome of the study was PN completion. We used a multivariable logistic regression (MVA) model to investigate predictors of PN completion. We used SPARE score to assess tumor complexity. We used a bootstrap validation to compute the model's predictive accuracy. We investigated the relationship between the outcomes and specific predictors of interest such as tumor's complexity, approach and experience., Results: Of 675 patients, 360 (53%) were treated with PN vs. 315 (47%) with RN. Smaller tumors [Odds ratio (OR): 0.52, 95%CI 0.44-0.61; P < 0.001], lower SPARE score (OR: 0.67, 95%CI 0.47-0.94; P = 0.02), more experienced surgeons (OR: 1.01, 95%CI 1.00-1.02; P < 0.01), robotic (OR: 10; P < 0.001) and open (OR: 36; P < 0.001) compared to laparoscopic approach resulted associated with higher probability of PN completion. Predictive accuracy of the model was 0.94 (95% CI 0.93-0.95)., Conclusions: The probability of PN completion can be preoperatively assessed, with optimal accuracy relaying on routinely available clinical information. The proposed model might be useful in preoperative decision-making, patient consensus, or during preoperative counselling., Patient Summary: In patients with a renal mass the probability of completing a partial nephrectomy varies considerably and without a predictive model is invariably inaccurate and subjective. In this study we build-up a risk calculator based on easily available preoperative variables that can predict with optimal accuracy the probability of not removing the entire kidney., Competing Interests: Declaration of competing interest A. Necchi reports honoraria from Roche, Merck Sharp & Dohme, AstraZeneca, Janssen Pharmaceuticals and Foundation Medicine; has served as a consultant or advisor for Merck Sharp & Dohme, Bristol-Myers Squibb, Rainier Therapeutics, Roche, Bayer, AstraZeneca, Clovis Oncology, Janssen Pharmaceuticals, Incyte, Seattle Genetics, Astellas Pharma and Rainier Therapeutics; has received research funding from Incyte, Merck Sharp & Dohme (institution), and AstraZeneca (institution); and has received travel funding from Roche, Merck Sharp & Dohme, Astra Zeneca, and Janssen Pharmaceuticals outside the submitted work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Up to 15% of patients with locally advanced renal cell carcinoma (RCC) harbors tumor thrombus (TT). In those cases, radical nephrectomy (RN) and thrombectomy represents the standard of care. We assessed the impact of TT on long-term functional and oncological outcomes in a large contemporary cohort., Methods: Within a prospective maintained database, 1207 patients undergoing RN for non-metastatic RCC between 2000 and 2021 at a single tertiary centre were identified. Of these, 172 (14%) harbored TT. Multivariable logistic regression analyses evaluated the impact of TT on the risk of postoperative acute kidney injury (AKI). Multivariable Poisson regression analyses estimated the risk of long-term chronic kidney disease (CKD). Kaplan Meier plots estimated disease-free survival and cancer specific survival. Multivariable Cox regression models assessed the main predictors of clinical progression (CP) and cancer specific mortality (CSM)., Results: Patients with TT showed lower BMI (24 vs. 26 kg/m 2 ) and preoperative Hb (11 vs. 14 g/mL; all-p < 0.05). Clinical tumor size was higher in patients with TT (9.6 vs. 6.5 cm; p < 0.001). After adjusting for potential confounders, the presence of TT was significantly associated with a higher risk of postoperative AKI (OR 2.03, 95% CI 1.49-3.6; p < 0.001) and long-term CKD (OR: 1.32, 95% CI 1.10-1.58; p < 0.01). Notably, patients with TT showed worse long-term oncological outcomes and TT was a predictor for CP (2.02, CI 95% 1.49-2.73, p < 0.001) and CSM (HR 1.61, CI 95% 1.04-2.49, p < 0.03)., Conclusions: The presence of TT in RCC patients represents a key risk factor for worse perioperative, as well as long-term renal function. Specifically, patients with TT harbor a significant and early estimated glomerular filtration rate (eGFR) decrease. However, despite TT patients show a greater eGFR decline after surgery, they retain acceptable renal function, which remains stable over time., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Compressing light into nanocavities substantially enhances light-matter interactions, which has been a major driver for nanostructured materials research. However, extreme confinement generally comes at the cost of absorption and low resonator quality factors. Here we suggest an alternative optical multimodal confinement mechanism, unlocking the potential of hyperbolic phonon polaritons in isotopically pure hexagonal boron nitride. We produce deep-subwavelength cavities and demonstrate several orders of magnitude improvement in confinement, with estimated Purcell factors exceeding 10 8 and quality factors in the 50-480 range, values approaching the intrinsic quality factor of hexagonal boron nitride polaritons. Intriguingly, the quality factors we obtain exceed the maximum predicted by impedance-mismatch considerations, indicating that confinement is boosted by higher-order modes. We expect that our multimodal approach to nanoscale polariton manipulation will have far-reaching implications for ultrastrong light-matter interactions, mid-infrared nonlinear optics and nanoscale sensors., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: To test the hypothesis that longer warm ischaemia time (WIT) might have a marginal impact on renal functional outcomes and might, in fact, reduce haemorrhagic risk intra-operatively., Patients and Methods: Data from 1140 patients treated with elective partial nephrectomy (PN) for a cT1-2 cN0 cM0 renal mass were prospectively collected. WIT was defined as the duration of clamping of the main renal artery with no refrigeration and was tested as a continuous variable. The primary outcome of the study was evaluation of the effect of WIT on renal function (estimated glomerular filtration rate [eGFR]) postoperatively, at 6 months and in the long term (measured between 1 and 5 years after surgery). The secondary outcome of the study was haemorrhagic risk, defined as estimated blood loss (EBL) or peri-operative transfusions. Multivariable linear, logistic and Cox regression analyses, accounting for age, Charlson comorbidity index, clinical size, preoperative eGFR and year of surgery, were used and the potential nonlinear relationship between WIT and the study outcomes was modelled using restricted cubic splines., Results: A total of 863 patients (76%) underwent PN with WIT and 277 (24%) without. The baseline median eGFR was 87.3 (68.8-99.2) mL/min/1.73m 2 for the on-clamp population and 80.6 (63.2-95.2) mL/min/1.73m 2  for the off-clamp population. The median duration of WIT was 17 (13-21) min. At multivariable analyses predicting renal function, longer WIT was associated with decreased postoperative eGFR (estimate: -0.21, 95% confidence interval [CI] -0.31; -0.11 [P < 0.001]). Conversely, no association between WIT and eGFR was recorded at 6-month or long-term follow-up (all P > 0.8). At multivariable analyses predicting haemorrhagic risk, clampless resection with no ischaemia time and PN with short WIT was associated with an increased EBL (estimate: -21.56, 95% CI -28.33; -14.79 [P < 0.001]) and peri-operative transfusion rate (estimate: -0.009, 95% CI -0.01; -0.003 [P = 0.002]). No association between WIT and positive surgical margin status was recorded (all P = 0.1)., Conclusion: Patients and clinicians should be aware that performing PN with very limited or even with zero WIT might increase bleeding and the need for peri-operative transfusion while not improving long-term renal function outcomes., (© 2023 BJU International.)

Mounting experimental evidence from in vitro and in vivo animal studies points to an essential role of the CXCL8-CXCR1/2 axis in neutrophils in the pathophysiology of inflammatory and autoimmune diseases. In addition, the pathogenetic involvement of neutrophils and the CXCL8-CXCR1/2 axis in cancer progression and metastasis is increasingly recognized. Consequently, therapeutic targeting of CXCR1/2 or CXCL8 has been intensively investigated in recent years using a wide array of in vitro and animal disease models. While a significant benefit for patients with unwanted neutrophil-mediated inflammatory conditions may be expected from a potential clinical use of inhibitors, their use in severe infections or sepsis might be problematic and should be carefully and thoroughly evaluated in animal models and clinical trials. Translating the approaches using inhibitors of the CXCL8-CXCR1/2 axis to cancer therapy is definitively a new and promising research avenue, which parallels the ongoing efforts to clearly define the involvement of neutrophils and the CXCL8-CXCR1/2 axis in neoplastic diseases. Our narrative review summarizes the current literature on the activation and inhibition of these receptors in neutrophils, key inhibitor classes for CXCR2 and the therapeutic relevance of CXCR2 inhibition focusing here on gastrointestinal diseases., (© 2023. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Background: The role of lymph node dissection (LND) in patients with renal cell carcinoma (RCC) is still controversial. However, detecting lymph node invasion (LNI) is key due to prognostic implications and to identify patients who might benefit from adjuvant therapies such as adjuvant pembrolizumab., Materials and Methods: Out of 796 patients, 261 (33%) received eLND, of whom 62 (8%) for suspicious lymph node (LN) metastases at preoperative staging (cN1). eLND was divided in 3 anatomical areas: (1) hilar, (2) side-specific (pre-/para-aortic or pre-/para-caval) and (3) inter-aorto-caval nodes. Overall maximum LN diameter was measured by a dedicated radiologist for each patient. Multivariable logistic regression models (MVA) were tested for the effect of maximum LN diameter in predicting the presence of nodal metastases outside the anatomical area of cN1., Results: LNI was confirmed in 50% of cN1, whilst only 13 out of 199 cN0 patients were pN1 at final histology (6.5%; p < 0.001). In a per-patient analysis, of 62 cN1 patients, 24% vs. 18% vs. 8% harboured pN1 disease only inside vs. in-outside vs. only outside the suspicious anatomical field of cN1 at preoperative CT/MRI scan. At MVA, increasing diameter of suspicious LNs was independently associated with risk of finding positive LNs outside the suspicious anatomical field (OR 1.05, 95%CI 1.02-1.11; p = 0.02)., Conclusions: Roughly 50% of cN1 patients undergoing eLND will harbour LN metastases, also outside the suspicious radiological area, and maximum LNs diameter at preoperative imaging correlates with such risk. Thus, an eLND might be justified in patients with large suspicious LN metastases, to better stage this patient population and to improve postoperative treatment management., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Partial nephrectomy (PN) is a challenging procedure, which can be associated with severe complications. In consequence, the search for accurate and independent indicators of unfavorable surgical outcomes appears warranted. We aimed at evaluating the impact of frailty status on surgical, functional and oncologic outcomes in patients undergoing PN for renal cell carcinoma (RCC)., Methods: A retrospective, single-center study including 1,282 patients treated with PN for clinically localized cT 1 RCC was performed. The modified Frailty Index (mFI) was used to assess preoperative frailty. Multivariable logistic, Poisson and linear regression analyses(MVA) tested the effect of frailty on complications, acute kidney injury(AKI), renal function decline after PN. Cumulative incidence and competing-risk analyses investigated survival outcomes., Results: Of 1,282 patients, 220 (17%) were frail. Overall, 982 (76%) vs. 123 (9.6%) vs. 171 (13%) patients underwent open vs. laparoscopic vs. robot-assisted PN. Median follow-up was 66 (IQR: 35-107) months. At MVA, frailty status predicted increased risk of complications [Odds ratio (OR): 1.46, 95%CI 1.17-1.84; P < 0.001]. Moreover, frail patients were at higher risk of postoperative AKI (OR: 1.95, 95%CI 1.13-3.35; P = 0.01). In frail patients, renal function permanently decreased over time (P = 0.01) without any renal function plateau or improvement during the follow-up, which were instead observed in the nonfrail cohort. At competing-risks analyses, frailty status predicted higher risk of other-cause mortality [Hazard ratio (HR): 1.67, 95%CI 1.05-2.66; P = 0.02], but not of cancer-specific mortality (P = 0.3)., Conclusions: Frailty status predicts higher risk of adverse surgical outcomes after PN. Moreover, greater renal function decline was observed in frail patients, compared with nonfrail patients. Finally, the risk of OCM significantly overcomes the risk of dying due to RCC in frail patients., Competing Interests: Conflict of interest statement All authors declare no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Although radical nephrectomy (RN) is the most common treatment for kidney cancer, no data on the learning curve for RN are available. In this study we investigated the effect of surgical experience (EXP) on RN outcomes using data for 1184 patients treated with RN for a cT1-3a cN0 cM0 renal mass. EXP was defined as the total number of RNs performed by each surgeon before the patient's operation. The primary study outcomes were all-cause mortality, clinical progression, Clavien-Dindo grade ≥2 postoperative complications (CD ≥2), and the estimated glomerular filtration rate (eGFR). Secondary outcomes were operative time, estimated blood loss, and length of stay. Multivariable analyses adjusted for case mix revealed no evidence of association between EXP and all-cause mortality ( p = 0.7), clinical progression ( p = 0.2), CD ≥2 ( p = 0.6), or 12-mo eGFR ( p = 0.9). Conversely, EXP was associated with shorter operative time (estimate -0.9; p < 0.01). Mortality, cancer control, morbidity, and renal function might not be affected by EXP. The very large cohort examined and the extensive follow-up support the validity of these negative findings., Patient Summary: For patients with kidney cancer undergoing surgical removal of a kidney, those treated by novice surgeons have similar clinical outcomes to those treated by experienced surgeons. Thus, this procedure represents a convenient scenario for surgical training if longer operating theatre time can be planned., (© 2023 The Authors.)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein binds angiotensin-converting enzyme 2 as its primary infection mechanism. Interactions between S and endogenous proteins occur after infection but are not well understood. We profiled binding of S against >9000 human proteins and found an interaction between S and human estrogen receptor α (ERα). Using bioinformatics, supercomputing, and experimental assays, we identified a highly conserved and functional nuclear receptor coregulator (NRC) LXD-like motif on the S2 subunit. In cultured cells, S DNA transfection increased ERα cytoplasmic accumulation, and S treatment induced ER-dependent biological effects. Non-invasive imaging in SARS-CoV-2-infected hamsters localized lung pathology with increased ERα lung levels. Postmortem lung experiments from infected hamsters and humans confirmed an increase in cytoplasmic ERα and its colocalization with S in alveolar macrophages. These findings describe the discovery of a S-ERα interaction, imply a role for S as an NRC, and advance knowledge of SARS-CoV-2 biology and coronavirus disease 2019 pathology.

Purpose: The KEYNOTE-564 trial showed improved disease-free survival (DFS) for patients with high-risk renal cell carcinoma (RCC) receiving adjuvant pembrolizumab as compared to placebo. However, if systematically administered to all high-risk patients, it might lead to the overtreatment in a non-negligible proportion of patient. Therefore, we aimed to determine the optimal candidate for adjuvant pembrolizumab., Methods: Within a prospectively maintained database we selected patients who fulfilled the inclusion criteria of the KEYNOTE-564. We compared baseline characteristics and oncologic outcomes in this cohort with those of the placebo arm of the KEYNOTE-564. Regression tree analyses was used to generate a risk stratification tool to predict 1-year DFS after surgery., Results: In the off-trial setting, patients had worse tumor characteristics then in the KEYNOTE-564 placebo arm, i.e. there were more pT4 (5.4 vs. 2.7%, p = 0.046) and pN1 (15 vs. 6.3%, p < 0.001) cases. Median DFS was 29 (95% CI 21-35) months as compared to value not reached in KEYNOTE-564 and 1-year DFS was 64.2% (95% CI 59.6-69.2) as compared to 76.2% (95% CI 72.2-79.7), respectively. Patients with pN1 were at the highest risk of 1-year recurrence (1-year DFS 28.6% [95% CI 20.2-40.3]); patients without LNI, but necrosis were at intermediate risk (1-year DFS 62.5% [95% CI 56.9-68.8]); those without LNI and necrosis were at the lowest risk (1-year DFS 83.8% [95% CI 79.1-88.9]). LVI substratification furtherly improved the accuracy in the prediction of early recurrence., Conclusions: Patients potentially eligible for adjuvant pembrolizumab have worse characteristics and DFS in the off-trial setting as compared to the placebo arm of the KEYNOTE-564. Patients with either LNI or necrosis were at the highest risk of early-recurrence, which make them the ideal candidate to adjuvant pembrolizumab., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: The impact of open versus minimally invasive surgery on recurrence pattern in the management of localized renal cell carcinoma (RCC) remains uncertain. We thus aimed to determine the impact of surgical approach on survival and recurrence pattern., Material and Methods: This is a multi-institutional, matched cohort study on patients with pT1-3aN0M0 RCC from the RECUR database. After propensity score matching between open and minimally invasive surgery, disease-free (DFS) survival and risk of first recurrence according to recurrence site, namely local recurrence, abdominal/retroperitoneal, thoracic/mediastinal or uncommon site metastases were investigated with Cox regression analysis. Overall (OS) and Cancer Specific Survival (CSS) were also assessed., Results: After matching, 1,019 patients who underwent open and 1,019 who underwent minimally invasive surgery were included (of which 70 robot-assisted). At 5.2 years of median follow-up, 130 patients in open and 125 in minimally invasive group experienced disease progression. A higher risk of local recurrence (HR 2.06; 95% CI 1.18-3.58, P-value = 0.01) and uncommon site metastases (HR 1.09; 95% CI 1.01-1.16; P-value = .04) was found for minimally invasive surgery relative to open surgery, while no difference was found in terms of DFS (HR 0.83; 95% CI 0.64-1.06; P-value = .14). No differences were found in terms of OS and CSS. Main limitation is the retrospective nature of the study., Conclusions: The risk for local recurrence and uncommon site metastases was higher for minimally invasive surgery compared to open surgery, although no differences were found for OS, CSS, and DFS., Competing Interests: Conflict of interest None, (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Despite papillary renal cell carcinoma (pRCC) subtype represents the second most common histological renal tumor, controversial findings have been shown regarding its prognosis. Thus, we investigated the natural history of patients harbouring pRCC, focusing on its clinicopathological characteristics and long-term oncologic outcomes among pRCC subtypes., Materials and Methods: We identified 447 patients treated with either partial (PN) or radical nephrectomy (RN) for pRCC at a single tertiary centre, between 1994 and 2019. First, we explored differences in baseline and clinicopathological characteristics. Second, Kaplan-Meier plots investigated progression-free survival (PFS) and cancer-specific survival (CSS) differences among pRCC subtypes. Third, multivariable Cox-regression analyses (MVA) were used to assess predictors of clinical progression (CP) and cancer-specific mortality (CSM)., Results: Overall, 120 (27%) patients had symptoms at time of diagnosis. 263 (58.8%) vs. 184 (41.2%) patients underwent PN vs. RN. At histopathological evaluation, 243 (54.4%) harboured pRCC type I vs. 204 (45.6%) type II. pRCC type II more frequently showed higher tumor grade, tumor necrosis or lymphovascular invasion (all P<0.001). After a median follow-up of 51 months, 2.5% and 11% of patients had local relapse and CP, respectively. Kaplan-Meier plots revealed 93 vs. 83% 5-year PFS (P<0.001) and 96 vs. 89% 5-year CSS (P=0.01) for non-metastatic pRCC type I vs. II, respectively. At MVA, pRCC type II predicted higher risk of CP (Hazard ratio [HR]: 3.03, 95%CI 1.42-6.44; P=0.01), as well as of CSM (HR: 2.60, 95%CI 1.05-6.29; P=0.02), relative to pRCC type I., Conclusions: PRCC type II harbour more unfavorable tumor characteristics, such as higher tumor grade, more frequent tumor necrosis or lymphvascular invasion, which translates into worse long-term oncologic outcomes, compared with pRCC type I. Thus, patients harbouring pRCC type II may benefit from stricter follow-up, as well as earlier risk-based adjuvant therapies, based on potential worse oncologic outcomes in this patient population., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To examine the effect of frailty on short-term post-operative outcomes and total hospital charges (THCs) in patients with non-metastatic renal cell carcinoma, treated with partial nephrectomy (PN)., Methods: Within the National Inpatient Sample (NIS) database we identified 25,545 patients treated with PN from 2000 to 2015. We used the Johns Hopkins Adjusted Clinical Groups (ACG) frailty-defining indicator and we examined the rates of frailty over time, as well as its effect on overall complications, major complications, blood transfusions, non-home-based discharge, length of stay (LOS) and THCs. Time trends and multivariable logistic, Poisson and linear regression models were applied., Results: Overall, 3574 (14.0%) patients were frail, 2677 (10.5%) were older than 75 years and 2888 (11.3%) had Charlson comorbidity index (CCI) ≥ 2. However, the vast majority of frail patients were neither elderly nor comorbid (83%). Rates of frail patients treated with PN increased over time, from 8.3 in 2000 to 18.1% in 2015 (all p &lt; 0.001). Frail patients showed higher rates of overall complications (43.5 vs. 30.3%), major complications (16.6 vs. 9.8%), blood transfusions (11.6 vs 8.3%) and non-home-based discharge (9.9 vs. 5.4%). longer LOS [4 (IQR: 3-6) vs. 4 (IQR: 2-5) days] and higher THCs ($43,906 vs. $38,447 - all p &lt; 0.001). Moreover, frailty status independently predicted overall complications (OR: 1.73), major complications (OR: 1.63), longer LOS (RR: 1.07) and higher THCs (RR: +$7506). Finally, a dose-response on the risk of suboptimal surgical outcomes was shown in patients with multiple risk factors., Conclusions: One out of seven patients is frail at time of surgery and this rate is on the rise. Moreover, frailty is associated with adverse outcomes after PN. In consequence, preoperative assessment of frailty status should be implemented, to identify patients who may benefit from pre- or postoperative measures aimed at improving surgical outcomes in this patient population., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Robot-assisted partial nephrectomy (RAPN) is increasingly adopted for the treatment of localized renal tumors; however, rates and predictors of significant renal function (RF) loss after RAPN are still poorly investigated, especially at a long-term evaluation., Objective: To analyze the predictive factors and develop a clinical nomogram for predicting the likelihood of ultimate RF loss after RAPN., Design, Setting, and Participants: We prospectively evaluated all patients treated with RAPN in a multicenter series (RECORd2 project)., Outcome Measurements and Statistical Analysis: Significant RF loss was defined as >25% reduction in estimated glomerular filtration rate (eGFR) from preoperative assessment at 48th month follow-up after surgery. Uni- and multivariable logistic regression analyses for RF loss were performed. The area under the receiving operator characteristic curve (AUC) was used to quantify predictive discrimination. A nomogram was created from the multivariable model., Results and Limitations: A total of 981 patients were included. The median age at surgery was 64.2 (interquartile range [IQR] 54.3-71.4) yr, and 62.4% of patients were male. The median Charlson Comorbidity Index (CCI) was 1 (IQR 0-2), 12.9% of patients suffered from diabetes mellitus, and 18.6% of patients showed peripheral vascular disease (PVD). The median Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) score was 7 (IQR 7-9). Imperative indications to partial nephrectomy were present in 3.6% of patients. Significant RF loss at 48th month postoperative evaluation was registered in 108 (11%) patients. At multivariable analysis, age (p = 0.04), female gender (p < 0.0001), CCI (p < 0.0001), CCI (p < 0.0001), diabetes (p < 0.0001), PVD (p < 0.0001), eGFR (p = 0.02), imperative (p = 0.001) surgical indication, and PADUA score (p < 0.0001) were found to be predictors of RF loss. The developed nomogram including these variables showed an AUC of 0.816., Conclusions: We developed a clinical nomogram for the prediction of late RF loss after RAPN using preoperative and surgical variables from a large multicenter dataset., Patient Summary: We developed a nomogram that could represent a clinical tool for early detection of patients at the highest risk of significant renal function impairment after robotic conservative surgery for renal tumors., (Copyright © 2022. Published by Elsevier B.V.)

Objectives: European Urology Association guidelines suggest the use of integrated prognostic systems to assess oncologic outcomes after surgery in patients with localized renal cell carcinoma (RCC). We performed a head-to-head comparison among all the EAU guidelines recommended prognostic models in RCC., Methods: The study included 2,014 patients treated with surgery for clinically localized RCC. Patients were classified into prognostic risk groups, based on each of the five EAU guidelines recommended prognostic model definition, namely UISS, Leibovich 2003, VENUSS, GRANT, and Leibovich 2018 score. Prognostic accuracy of each prognostic model to predict clinical progression or cancer-specific mortality (CSM) was assessed, and ROC curves were calculated, according to histological subtype, namely clear-cell, papillary, and chromophobe RCC., Results: Of 2,014 patients, 1,575 (78%) harboured clear-cell, 312 (16%) papillary, and 127 (6%) chromophobe RCC. Median follow-up was 66 months [Interquartile range (IQR): 29-120]. In clear-cell RCC, low-risk patients rates ranged from 21% to 64%, according prognostic model. The same phenomenon was observed for papillary and chromophobe RCC. In clear-cell RCC, Leibovich 2018 resulted the most accurate model in predicting clinical progression (88.1%) and CSM (86.8%). Conversely, VENUSS or UISS prognostic models predicting oncologic outcomes represented the most accurate in papillary (88.7% and 84.8%) or chromophobe (87.8% and 89.1%) RCC, respectively., Conclusions: A non-negligible difference in terms of performance accuracy exists among the EAU guidelines recommended prognostic models. Thus, their adoption in RCC should be histology-specific and follow-up strategies based on prognostic risk class appear justified only if the appropriate model is used to stratify patients into prognostic risk groups., Competing Interests: Declaration of Competing interest All authors declare no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Interstitial cystitis (IC)/bladder pain syndrome (BPS) is a chronic bladder disease of unknown etiology characterized by urinary frequency and episodic and chronic pain. Analgesic treatments for IC/BPS are limited, especially for patients with non-Hunner (non-ulcerative) type IC who usually have poor overall outcomes. Here, we demonstrate that oral treatment with DF2755A, a potent and selective inhibitor of chemokine receptors CXCR1/2, can prevent and reverse peripheral neuropathy associated to non-Hunner IC/BPS by directly inhibiting chemokine-induced excitation of sensory neurons. We tested DF2755A antinociceptive effects in a cyclophosphamide (CYP)-induced non-ulcerative IC rat model characterized by severe peripheral neuropathy in the absence of bladder inflammatory infiltrate, urothelial hyperplasia, and hemorrhage. Treatment with DF2755A prevented the onset of peripheral neuropathy and reversed its development in CYP-induced IC rats, showing a strong and long-lasting anti-hyperalgesic effect. Ex vivo and in vitro studies showed that DF2755A treatment strongly inhibited the expression of CXCR2 agonists, CXCL1/KC, and CXCL5 and of transient receptor potential vanilloid 1 (TRPV1) compared to vehicle, suggesting that its effects can be due to the inhibition of the nociceptive signaling passing through the CXCL1/CXCR1-2 axis and TRPV1. In conclusion, our results highlight the key pathophysiological role played by the CXCL1/CXCR1-2 axis and TRPV1 in the onset and development of peripheral neuropathy in non-Hunner IC and propose DF2755A as a potential therapeutic approach for the treatment of not only inflammatory painful conditions but also neuropathic ones and in particular non-Hunner IC/BPS., Competing Interests: The authors LB, AA, GB, AR, RN, and MA are employees of Dompe Farmaceutici S.p.A. R.B. is an employee of Atreius S.a.s and scientific advisor for Dompe Farmaceutici S.p.A. P.A. and A.E.V are employees of Recordati S. p.A. The other authors declare no conflict of interest. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Brandolini, Aramini, Bianchini, Ruocco, Bertini, Novelli, Angelico, Valsecchi, Russo, Castelli, Cimini and Allegretti.)

Background: The combination of radiomic and transcriptomic approaches for patients diagnosed with small clear-cell renal cell carcinoma (ccRCC) might improve decision making. In this pilot and methodological study, we investigate whether imaging features obtained from computed tomography (CT) may correlate with gene expression patterns in ccRCC patients., Methods: Samples from 6 patients who underwent partial nephrectomy for unilateral non-metastatic ccRCC were included in this pilot cohort. Transcriptomic analysis was conducted through RNA-sequencing on tumor samples, while radiologic features were obtained from pre-operative 4-phase contrast-enhanced CT. To evaluate the heterogeneity of the transcriptome, after a 1,000 re-sampling via bootstrapping, a first Principal Component Analyses (PCA) were fitted with all transcripts and a second ones with transcripts deriving from a list of 369 genes known to be associated with ccRCC from The Cancer Genome Atlas (TCGA). Significant pathways in each Principal Components for the 50 genes with the highest loadings absolute values were assessed with pathways enrichment analysis. In addition, Pearson's correlation coefficients among radiomic features themselves and between radiomic features and transcripts expression values were computed., Results: The transcriptomes of the analysed samples showed a high grade of heterogeneity. However, we found four radiogenomic patterns, in which the correlation between radiomic features and transcripts were statistically significant., Conclusions: We showed that radiogenomic approach is feasible, however its clinical meaning should be further investigated., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-21-713/coif). The authors have no conflicts of interest to declare., (2022 Translational Andrology and Urology. All rights reserved.)

The indications for adjuvant vascular endothelial growth factor-tyrosine kinase inhibitor (VEGF-TKI) agents after curative intent nephrectomy for renal cell carcinoma are still a matter of debate. The ASSURE, PROTECT and ATLAS trials have failed to meet their primary end-points. Conversely, S-TRAC has shown a disease free survival (DFS) benefit. To date, meta-analyses have repeatedly proved the absence of a clinical benefit, in term of DFS and overall survival (OS). Nevertheless, the results of the SORCE trial have been recently released and might add valuable information. We pooled the results of all five reported trials testing for any potential DFS and OS benefits associated with VEGF-TKI use. Interestingly, for pooled DFS we found a marginal positive hazard ratio (HR) of 0.92 (95% confidence interval [CI] 0.85-1.00; P-value = 0.049) in favor of adjuvant VEGF-TKI agents. This benefit was more pronounced for DFS in the sub-groups of only high-risk patients (HR: 0.89, 95% CI 0.80-0.99; P-value = 0.026), but less pronounced in clear-cell only subgroup (HR 0.92, 95% CI: 0.85-1.00; P-value = 0.044). Overall survival benefit was instead not reached. However, pooled relative risk for high-grade (grade ≥3 according to CTCAE classification) adverse events was irremediably high, 2.56 (95% CI: 2.15-3.04; P-value < 0.001). Given the marginal benefit in terms of DFS and the drawback of high-grade adverse events, even after the SORCE trial publication, adjuvant VEGF-TKIs therapy cannot be considered in the whole group of patients with non-metastatic high-risk renal cell carcinoma after surgery., (Copyright © 2021. Published by Elsevier Inc.)

Background: Scarce data are available regarding the technique and outcomes for patients with RCC and Mayo III caval thrombi. The aim of this study was to report surgical and oncological outcomes of RCC patients with Mayo III thrombi treated with radical nephrectomy and thrombectomy after liver mobilization (LM) and Pringle maneuver (PM)., Methods: Retrospective analysis of surgical technique, outcomes and cancer control in 19 patients undergoing LM and PM in a single tertiary care institution were analyzed., Results: Overall, 78% of the patients had performance status ECOG 1 and 58% had a Comorbidity Index >2. Median surgical time was 305 minutes (IQR 264-440). Intraoperative complications were reported for 39% of patients and postoperative complications for 58% (only grade 1 and 2). Intensive Care Unit support was necessary in 16% of the cases. Median length of hospital stay was 9 days (IQR: 7-11). Thirty- and 90-day mortality were 5% and 15%. Two-year overall survival and cancer-specific survival were 60% and 62%, respectively., Conclusions: We reported surgical techniques, intra- and perioperative complications and follow-up in the largest cohort of RCC patients requiring LM and PM.

Background: Partial nephrectomy (PN) for complex renal masses has a non-negligible risk of perioperative complications. Furthermore, late functional and oncological outcomes of patients submitted to these challenging surgeries still remain to be determined., Objectives: To report the perioperative and mid-term oncological and functional outcomes of PN for complex masses (Preoperative Aspects and Dimensions Used for an Anatomical [PADUA] score≥10) in a large multicenter prospective observational study., Design, Setting, and Participants: We prospectively evaluated patients treated with PN for complex renal tumors at 26 urological centers (Registry of Conservative and Radical Surgery for Cortical Renal Tumor Disease [RECORD2] project)., Outcome Measurements and Statistical Analysis: Multivariate logistic regression analyses explored the predictors of surgical complications. Multivariable Cox regression analyses estimated the hazard of renal function loss and disease recurrence. Kaplan-Meier estimates assessed the probability of survival., Results and Limitations: In total, 410 patients who underwent PN for complex masses were evaluated. Clinical T1b and T2 tumors accounted for 43.2% and 9.8% of the cases. Overall, 45.9%, 18.8%, and 35.4% of patients underwent open, laparoscopic, and robotic PN, respectively. Intraoperative complications occurred in 15 (3.6%) patients, while postoperative surgical complications were recorded in 76 (18.5%) patients. At multivariable analysis, preoperative hemoglobin (odds ratio [OR]: 0.67; p<0.001) and open (OR: 3.91; p<0.001) versus robotic surgical approach were found to be the only predictors of surgical complications. An estimated glomerular filtration rate drop of >25% from baseline was observed in 30.2% and 17.6% of patients at 1st month and 2 yr after surgery, respectively. Two-year recurrence-free survival was 97.1%; positive surgical margins (hazard ratio [HR]: 3.35; p=0.009), nucleolar grading (HR: 5.61; p<0.001), and tumor stage (HR: 2.62; p=0.05) were associated with recurrence., Conclusions: In a large series, PN for complex renal masses was a safe technique with an acceptable rate of perioperative complications and excellent mid-term oncological and functional results., Patient Summary: In this study, we evaluated peri- and postoperative outcomes of patients treated with partial nephrectomy for complex renal masses. Open surgery was associated with higher complications than the robotic approach. Some histological features were found to be associated with disease recurrence., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: The role of non-tumour renal biopsy in predicting renal function after surgery for renal cell carcinoma (RCC) is poorly investigated. The aim of the study was to assess the impact of renal parenchymal histology on renal function after radical nephrectomy in a cohort of patients with RCC., Methods: This cohort study included 171 patients with RCC submitted to radical nephrectomy between 2006 and 2018. Two biopsy samples from normal parenchyma were collected at nephrectomy and renal parenchyma damage (RPD) was scored on histologic samples according to validated methodology. The outcomes were eGFR after surgery and its reduction > 25% relative to baseline at maximum 12 months' follow-up. Linear and logistic multivariable regression were used, adjusting for age at surgery, presence of hypertension, diabetes, clinical tumour size, time from surgery and basal eGFR., Results: 171 patients were enrolled and RPD was demonstrated in 64 (37%). Patients with RPD had more comorbidities (CCI > 2 in 25 vs. 9%, p < 0.001), in particular hypertension (70 vs. 53%; p = 0.03), diabetes with (5% vs. 0%, p = 0.007) or without (31 vs. 18%; p = 0.007) organ damage, cerebrovascular disease (19 vs. 5%; p = 0.006) and nephropathy (20 vs. 3%; p = 0.0004). At multivariable analyses, RPD was associated with lower eGFR (Est. - 5.48; 95% CI - 9.27: - 1.7; p = 0.005) and with clinically significant reduction of eGFR after surgery (OR 3.06; 95% CI 1.17: 8.49; p = 0.026)., Conclusions: Presence of RPD in non-tumour renal tissue is an independent predictor of functional impairment in patients with RCC. Such preliminary finding supports the use of parenchyma biopsy during clinical decision making., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Background: Ischemia time during partial nephrectomy (PN) is among the greatest determinants of acute kidney injury (AKI). Whether this association is affected by the preoperative risk of AKI has never been investigated., Objective: To assess the effect of the interaction between the preoperative risk of AKI and ischemia time on the probability of AKI during PN., Design, Setting, and Participants: Data of 944 patients treated with on-clamp PN for cT1 renal tumors were extracted from the Registry of Conservative and Radical Surgery for Cortical Renal Tumor Disease (RECORD2) database, a prospective multicenter project., Outcome Measurements and Statistical Analysis: We estimated the preoperative risk of AKI (defined according to the risk/injury/failure/loss/end-stage [RIFLE] criteria) according to age, baseline renal function, clinical stage, preoperative aspects and dimensions used for an anatomical (PADUA) score, and surgical approach. Classification and regression tree (CART) analysis identified patients at "high" and "low" risk of AKI. Finally, we plotted the probability of AKI over ischemia time stratified by the preoperative risk of AKI., Results and Limitations: Overall, 235 (25%) patients experienced AKI after surgery. At multivariable analysis, older patients, those with more complex tumors, those with higher baseline function, and those treated with open surgery had an increased risk of AKI (all p ≤ 0.011). According to the first split at CART analysis, patients were categorized as those with "high" and "low" risk of AKI having a probability of >40% or <40%. For low-risk patients, the probability of AKI in case of <10 versus >20 min of ischemia was 13% versus 28% (absolute risk increase 15%). The risk of AKI for high-risk patients who had <10 versus >20 min of ischemia was 31% versus 77%. This corresponds to an absolute risk increase of 45%. Limitations include retrospective data analyses and lack of surgeons' prior experience., Conclusions: Ischemia time during PN has different implications for patients with different health status. Clamp time seems less clinically relevant for patients in good conditions who may endure prolonged ischemia with a mild increase in the risk of AKI, whereas frail patients seem to be more vulnerable to ischemic damage even for short clamp time. For individualized intra- and postoperative management, duration of ischemia needs to be questioned in the context of the individual health status., Patient Summary: Functional sequelae related to ischemia time during partial nephrectomy depend on baseline health status. The correlation between the duration of ischemia and baseline health status should be taken into account toward individualized intra- and postoperative management., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Acute kidney injury (AKI) and chronic kidney disease (CKD) are common events after radical nephrectomy (RN). In this study we aimed to predict AKI and CKD after RN relying on specific histological aspects. We collected data from a cohort of 144 patients who underwent radical nephrectomy. A histopathological review of the healthy part of the removed kidney was performed using an established chronicity score (CS). Logistic regression analyses were performed to predict AKI after RN, while linear regression analysis was adopted for estimated glomerular filtration rate (eGFR) variation at 1 year. The outcomes of the study were to determine variables correlated with AKI onset, and with eGFR decay at 1 year. The proportion of AKI was 64%. Logistic analyses showed that baseline eGFR independently predicted AKI (odds ratio 1.04, 95%CI 1.02:1.06). Moreover, AKI (Beta -16, 95%CI -21:-11), baseline eGFR (Beta -0.42, 95%CI -0.52:-0.33), and the presence of arterial narrowing (Beta 10, 95%CI 4:15) were independently associated with eGFR decline. Our findings showed that AKI onset and eGFR decline were more likely to occur with higher baseline eGFR and lower CS, highlighting that RN in normal renal function patients represents a more traumatic event than its CKD counterpart.

Purpose: The current literature regarding the effect of blood loss (eBL) after nephron-sparing surgery (NSS) on long-term renal function is scarce. We tested the effect of eBL on the risk of developing chronic kidney disease (CKD) after NSS., Methods: Within an institutional prospectively maintained database, we identified 215 patients treated with NSS for cT 1 N 0 M 0 renal mass at one European high-volume center. Multivariable logistic regression models tested the effect of eBL on the risk of developing CKD, after accounting for surgical complexity, individual clinical characteristics, and surgical experience. Multivariable linear regression models identified predictors of eBL., Results: After a median follow-up of 36 months, 55 (25.6%) patients experienced CKD after surgery. At multivariable analyses, eBL independently predicted higher risk of CKD after NSS (odds ratio [OR]: 1.16; 95% confidence intervals [CI] 1.04-1.30; p < 0.01). Specifically, the relationship between eBL and probability of CKD emerged as nonlinear, with a plateau from 0 to 500 mL of eBL and an increase afterward. When multivariable linear regression analyses investigated predictors of eBL, hypertension (Est: 127, 95% CI 12-242; p = 0.03), clinical size (Est: 47, 95% CI 7-87; p = 0.02), and PADUA score (Est: 42; 95% CI 4-80 p = 0.03) achieved independent predictor status for higher intraoperative eBL. Conversely, surgical experience was associated with lower eBL (p = 0.01)., Conclusions: Intraoperative bleeding is independently associated with the risk of developing CKD after surgery, even after adjustment for well-known predictors of renal failure and tumor complexity. Hence, strategies aimed at maximally reducing such adverse events deserve special consideration., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Surgical treatment of small renal masses (RMs) is still characterized by a non-negligible rate of benign histology, ultimately resulting in overtreatment. Since the risk of kidney cancer increases with age and the risk of malignancy usually increases with tumor size, we created a model based on patient age, RM size, and their interaction for predicting malignant histology. As male sex is associated with a higher risk of renal malignancy, we also stratified our analyses by sex. We used data for 2252 patients with cT1N0M0 disease (1551 male [69%], 701 female [31%]). On logistic regression, both age and RM size were predictors of malignant histology. For males, the odds ratio (OR) was 1.82 (95% confidence interval [CI] 1.78-2.80) for age and 2.04 (95% CI 1.69-2.47) for RM size; for females, the OR was 1.82 (95% CI 1.78-2.80) for age and 2.04 (95% CI 1.69-2.47) for RM size (all p ≤ 0.007), with a significant continuous-by-continuous interaction between them (p < 0.001) in both models. On decision curve analysis, the model demonstrated clinical utility for predicting malignancy at a probability of <55% for males and <60% for females. Individuals with lower probability should be considered for renal biopsy and those with higher probability for upfront surgery. The model was also more informative than RM size alone in predicting malignancy, which currently represents the only absolute criterion for active surveillance eligibility. PATIENT SUMMARY: In this study we analyzed the correlation between age and tumor size for predicting tumor malignancy. The aim in management is to balance the utility of performing a biopsy and the appropriateness of upfront surgery against the ultimate goal of decreasing overtreatment., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

We hypothesized that pT3a stage at nephrectomy can be accurately predicted in cT1N0M0 clear cell-renal cell carcinoma (cc-RCC) patients. Of 236 patients, treated with either partial or radical nephrectomy (2005-2019), 25 (10.6%) harbored pT3a stage. Multivariable logistic regression models predicting pT3a were fitted using age, tumor size, tumor location and exophytic rate. The new model was 81% accurate. In calibration plots, minimal departures from ideal prediction were recorded. In decision curve analyses, a net-benefit throughout all threshold probabilities was recorded relative to the treat-all or treat-none strategies. Using a probability cut-off of 21% for presence of pT3a stage, 38 patients (16.1%) were identified, in whom pT3a rate was 36.8%. Conversely, in 198 patients (83.9%) below that cut-off, the rate of pT3a was 5.6%. Alternative user-defined cut-offs may be selected. The new model more accurately identifies a subgroup of cT1N0M0 cc-RCC patients with substantially higher risk of pT3a stage than average., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Partial nephrectomy (PN) has a non-negligible perioperative morbidity. Comparative evidence of the available surgical techniques is limited., Objective: To compare the perioperative outcomes of open, laparoscopic, and robotic PN., Methods: Data of 2331 patients treated with PN for cT1 renal tumors were extracted from the RECORd2 database, a prospective multicenter project. Multivariable regression models assessed the relationship between surgical technique and surgical margins, warm ischemia time, postoperative complications, and acute kidney injury (AKI). The probability of achieving a modified trifecta (negative margins, warm ischemia time <25min, and no Clavien-Dindo ≥2 complications) was examined for each surgical approach., Results: Minimally invasive techniques had lower rate of Clavien-Dindo ≥2 complications than that of open surgery (odds ratio [OR] for robotic surgery: 0.27; 95% confidence interval [95% CI]: 0.15-0.47, p< 0.0001; OR for laparoscopy: 0.52; 95% CI: 0.34-0.78; p= 0.002). The probability of receiving ischemia was highest for robotic PN (p< 0.001). Among on-clamp PN, laparoscopy had longer ischemia than open (estimate: 1.09; 95% CI: -0.00 to 2.18; p= 0.050) and robotic (estimate: 1.36; 95% CI: 0.31-2.40; p= 0.011) surgery. When compared with open PN, the risk of AKI was roughly halved for patients treated by robotic and laparoscopic surgery (both p< 0.0001). Positive margins rate did not differ between the groups (all p≥ 0.1). The likelihood to achieve a modified trifecta was not affected by surgical technique in the overall population (all p≥ 0.075). In Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) score < 10 lesions, robotic surgery had higher probability of achieving a modified trifecta than open PN (OR: 1.66; 95% CI: 1.09-2.53; p= 0.018) and laparoscopy (OR: 1.34; 95% CI: 0.94-1.90; p= 0.11)., Conclusions: In PADUA<10 renal tumors, robotic PN allows for higher rates of trifecta than open and laparoscopic surgeries. The impact of surgical technique on perioperative outcomes of PN might be limited in more complex lesions., Patient Summary: We evaluated the association between surgical technique and perioperative outcomes of partial nephrectomy. In less complex (Preoperative Aspects and Dimensions Used for an Anatomical [PADUA] score < 10) lesions, robotic PN allows for higher rates of trifecta when compared with other surgical techniques., (Copyright © 2019. Published by Elsevier B.V.)

Background: The accurate detection of nodal invasion is an unmet need in the clinical staging of renal cancer. Positron emission tomography (PET) with 18F-fluoroazomycin arabinoside (18F-FAZA), a hypoxia specific tracer, is a non-invasive imaging method that detects tumour hypoxia. The aim of this work was to evaluate the role of 18F-FAZA PET/CT in the identification of lymph node metastases in renal cancer., Methods: A proof-of-concept phase 2 study including 20 kidney cancer patients ( ClinicalTrials.gov Identifier: NCT03955393) was conducted. Inclusion criteria were one or more of the following three criteria: (1) clinical tumour size > 10 cm, (2) evidence of clinical lymphadenopathies at preoperative CT scan and (3) clinical T4 cancer. Before surgery, 18F-FAZA PET/CT was performed, 2 h after the intravenous injection of the radiotracer. An experienced nuclear medicine physician, aware of patient's history and of all available diagnostic imaging, performed a qualitative and semi-quantitative analysis on 18F-FAZA images. Histopathological analysis was obtained in all patients on surgical specimen., Results: Fourteen/19 (74%) patients had a non-organ confined renal cell carcinoma (RCC) at final pathology (either pT3 or pT4). Median number of nodes removed was 12 (IQR 7-15). The rate of lymph node invasion was 16%. No patient with pN1 disease showed positive 18F-FAZA PET, thus suggesting the non-hypoxic behaviour of the lesions. In addition, neither primary tumour nor distant metastases presented a pathological 18F-FAZA uptake. No adverse events were recorded during the study., Conclusions: 18F-FAZA PET/CT scan did not detect RCC lymph neither nodal nor distant metastases and did not show any uptake in the primary renal tumour.

The role of cytoreductive nephrectomy (CN) patients with metastatic renal cell carcinoma (mRCC) is unclear. To define the proportion of symptomatic mRCC, to investigate the impact of CN on symptomatic improvement and perioperative morbidity, and to elucidate the trade-off between such benefit and harm, an observational study of 317 mRCC patients treated with CN was performed. Symptomatic mRCC was defined as the presence of any sign or symptom causally related to the disease. Sign or symptom resolution and improvement were defined as the absence of all the signs and symptoms recorded at baseline, and the absence of at least one sign or symptom recorded at baseline, respectively. Perioperative morbidity was assessed using the Clavien-Dindo classification. Response to CN was classified as beneficial, mixed, or harmful according to the trade-off between symptomatic improvement and perioperative morbidity. The proportions of local, metastasis-specific, and general signs or symptoms were 37%, 23%, and 27%, respectively. The proportions of any sign or symptom resolution and improvement after CN were 43% and 71%, respectively. The proportions of local sign or symptom resolution and improvement after CN were 91% and 95%, respectively. The risks of any complication and major complication were 37% and 10%, respectively. At regression analysis, symptomatic status was not associated with perioperative morbidity. The proportion of beneficial response was invariably higher than the proportion of harmful response. At mRCC diagnosis, two out of three patients suffer from any sign or symptom, and one out of three suffers from local signs or symptoms. CN has a positive impact on symptomatic status. PATIENT SUMMARY: Most metastatic renal cell carcinoma patients are symptomatic, and they should be aware that cytoreductive nephrectomy has a positive impact on symptomatic status., (Copyright © 2020. Published by Elsevier B.V.)

Background: Despite better renal function following nephron-sparing surgery (NSS) relative to radical nephrectomy (RN), there is no consensus with respect to the long-term sequelae associated with surgery., Objective: To investigate the effect of surgery and the temporal pattern of two different cardiovascular event (CVe) categories after NSS versus RN., Design, Setting, and Participants: We collected data of 898 patients with cT1-2 N0 M0 renal mass and no history of CVe treated with NSS versus RN. CVe categories were dichotomised in (1) de novo hypertension (HT) and (2) other major cardiovascular events (MCEs)., Outcome Measurements and Statistical Analysis: Multivariable competing regression analyses (MVAs) tested the adjusted effect of surgery type on each CVe category., Results and Limitations: Among patients treated with RN, 38% of HT events occurred immediately after surgery. Conversely, in NSS counterparts, the onset of HT was diluted over the years after surgery (10% of HT events in the first 6 mo). When an MCE was considered, an increasing long-term time-dependent prevalence of the outcome was observed in both groups, with no statistically significantly difference between NSS and RN. At MVA, RN was associated with a higher HT risk (hazard ratio [HR] 2.89; p=0.006) than but a similar MCE risk (HR 0.85; p=0.6) to NSS., Conclusions: Relative to RN, NSS showed an independent protective effect on HT but not on MCEs. In patients with no history of preoperative HT or MCEs, the onset of HT after RN is a very early event, due probably to the acute loss of renal parenchyma. This is not the case for the other cardiovascular morbidity, which develops in the long-term period, regardless of the type of surgery performed., Patient Summary: In renal cancer patients without a medical history of cardiopathy, preserving healthy kidney tissue at surgery is associated with a decreased risk of developing postoperative hypertension., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: Radiofrequency and cryoablation (Cryo) are the most widely used techniques for the treatment of T1a renal tumors in non-surgical candidates, yet microwave ablation (MWA) has been gaining popularity. In this study, we tested the hypothesis that MWA has comparable safety and efficacy to Cryo in the treatment of selected T1a renal masses., Materials and Methods: A retrospective comparative analysis of two patient cohorts was carried out on 83 nodules in 72 consecutive patients treated using image-guided percutaneous ablation with either Cryo or MWA. Patient demographics, tumor histology and characteristics, technical success, procedure time, adverse events and complications, nephrometry score (mRENAL) and renal function were evaluated. Local recurrence was evaluated at 1, 6, 12 and 18-24 months., Results: Fifty-one nodules were treated with Cryo and 32 with MWA (44 and 28 patients, respectively). No statistical differences were observed following Cryo or MWA in median tumor size (p = 0.6), mRENAL (p = 0.1) or technical success (p = 0.8). Median procedure time was significantly lower using microwave ablation (p = 0.003). Median follow-up time was similar in the two groups (22 and 20 months, respectively). Occurrence of complications did not differ (Cryo 5/51, MWA 2/32; p = 0.57), and probability of complications or technical success adjusted for mRENAL did not reach statistical significance (p = 0.6). Renal function was preserved in all patients regardless of techniques. Disease recurrence was observed in 3/47 and in 1/30 treated nodules in the Cryo and MWA groups, respectively, without reaching statistical significance (p = 0.06)., Conclusion: In the patient population studied, MWA showed comparable safety and efficacy relative to Cryo., Level of Evidence: Level 3, Non-randomized cohort study.

Objectives: To compare long-term functional outcomes of off-clamp or on-clamp partial nephrectomy patients of two high-volume centers with cT1-2/N0 M0 renal tumors and baseline estimated glomerular filtration rate >60 mL/min., Methods: A 3:1 propensity score-matched analysis was used to select two homogeneous cohorts to compare off-clamp versus on-clamp partial nephrectomy. Joinpoint regression analysis was used to compare the 2-8-year probabilities of estimated glomerular filtration rate modifications in both selected cohorts. The Kaplan-Meier method assessed the risk of developing a stage ≥3b chronic kidney disease during follow up. Multivariable analyses aimed to identify predictors of renal function deterioration. Perioperative complications and oncological outcomes were compared., Results: Overall, 1073 patients were included (588 on-clamp and 485 off-clamp). After applying the propensity score-matched analysis, the two cohorts of 157 on-clamp and 472 off-clamp patients did not differ for all covariates, except for warm ischemia time and last estimated glomerular filtration rate. At joinpoint analysis, the off-clamp group showed higher probabilities of maintaining an unmodified estimated glomerular filtration rate (P = 0.02). The probability of developing a stage ≥3b chronic kidney disease was significantly higher (P < 0.001) in the on-clamp cohort. At multivariable analysis, estimated glomerular filtration rate at discharge and off-clamp approach were independent predictors of improved functional outcomes. Perioperative complications were comparable among the two cohorts (P = 0.67). There were not any statistically significant differences in terms of cancer-specific survival (P = 0.26) and overall survival (P = 0.18)., Conclusions: Off-clamp partial nephrectomy seems to offer a higher probability of maintaining 100% estimated glomerular filtration rate after surgery. In our cohort, patients undergoing on-clamp partial nephrectomy presented a 7.3-fold increased risk of developing a severe chronic kidney disease during follow up., (© 2019 The Japanese Urological Association.)

Objectives: To investigate whether postoperative complications affect long-term functional outcomes of renal patients treated with nephron-sparing surgery (NSS)., Materials and Methods: We performed an observational study, enrolling 596 patients with preoperative normal renal function treated with NSS for clinical T1abN0M0 renal masses. Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for chronic kidney disease (CKD) including as covariates age, comorbidity (scored according to the Charlson comorbidity index), hypertension, tumour size, preoperative estimated glomerular filtration rate (eGFR), eGFR < 60 mL/min/1.73 m 2 at discharge, and ischaemia time., Results: A total of 137 patients (23%) developed postoperative complications. At a median (interquartile range) follow-up of 53 (26-91) months, CKD risk was 19% for patients with postoperative complications and 11% for those without complications. Patients experiencing postoperative complications (HR 1.90, 95% CI 1.26-2.86) were at increased risk of developing CKD during the follow-up at multivariable analysis, after accounting for confounders., Conclusions: Our data outline how postoperative complications might have a detrimental impact on postoperative renal function in patients submitted to NSS. Improper patient selection, increasing the risk of postoperative complications, could limit the benefit in terms of renal function brought by NSS., (© 2019 The Authors BJU International © 2019 BJU International Published by John Wiley & Sons Ltd.)

Purpose: To evaluate the role of side and location of the primary renal cell carcinoma (RCC) on the risk of lymph node invasion (LNI) and/or nodal progression (NP) during follow-up., Materials and Methods: We evaluated 2485 patients with unilateral RCC, surgically treated in a single tertiary care referral center. Outcomes were LNI at surgery and/or NP during follow-up. We studied if RCC side (left vs. right) and location (upper vs. middle vs. hilar vs. lower area vs. more than one area) affected the probability of LNI and/or NP at follow-up., Results: Overall, 43 and 15% of patients underwent lymph node dissection and had LNI at surgery, respectively. During follow-up, 2.2% of patients had NP. Higher rates of LNI and NP were observed for patients with primary tumor located in more than one anatomical kidney area relative to patients with tumor in a single area (upper 11% vs. middle 10% vs. hilar 0%, vs. lower 12% vs. more than one area 26%, p < 0.01). cM1, cN1, pT2/pT3/pT4 disease and Fuhrman grade 3/4 were independent predictors of the study outcome (all p ≤ 0.01). Neither the RCC side nor the location reached the independent predictor status (all p > 0.1)., Conclusions: Patients with single-side and more than one anatomical kidney area affected by RCC have higher rate of LNI at surgery and/or NP at follow-up. Neither side nor location of primary RCC tumor is related to the risk of harboring LNI at surgery and/or developing NP at follow-up.

Objective: To identify meaningful predictors and to develop a nomogram of postoperative surgical complications in patients treated with partial nephrectomy (PN)., Patients and Methods: We prospectively evaluated 4308 consecutive patients who had surgical treatment for renal tumours, between 2013 and 2016, at 26 Italian urological centres (RECORd 2 project). A multivariable logistic regression for surgical complications was performed. A nomogram was created from the multivariable model. Internal validation processes were performed using bootstrapping with 1000 repetitions., Results: Overall, 2584 patients who underwent PN were evaluated for the final analyses. The median (interquartile [IQR]) American Society of Anesthesiologists (ASA) score was 2 (2-3). In all, 72.4% of patients had clinical T1a (cT1a) stage tumours. The median (IQR) Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) score was 7 (6-8). Overall, 34.3%, 27.7%, 38% of patients underwent open PN (OPN), laparoscopic PN (LPN), and robot-assisted PN (RAPN). Overall and major postoperative surgical complications were recorded in 10.2% and 2.5% of patients, respectively. At multivariable analysis, age, ASA score, cT2 vs cT1a stage, PADUA score, preoperative anaemia, OPN and LPN vs RAPN, were significant predictive factors of postoperative surgical complications. We used these variables to construct a nomogram for predicting the risk of postoperative surgical complications. At decision curve analysis, the nomogram led to superior outcomes for any decision associated with a threshold probability of >5%., Conclusion: Several clinical predictors have been associated with postoperative surgical complications after PN. We used this information to develop and internally validate a nomogram to predict such risk., (© 2019 The Authors BJU International © 2019 BJU International Published by John Wiley & Sons Ltd.)

Purpose: A significant proportion of patients affected by renal cell carcinoma (RCC) shows a suspicious lymph node involvement (LNI) at preoperative imaging. We sought to evaluate the effect of lymphadenopathies (cN1) on survival in surgical RCC patients with no evidence of LNI at final pathology (pN0)., Methods: 719 patients underwent either radical or partial nephrectomy and lymph node dissection at a single tertiary care referral centre between 1987 and 2015. All patients had pathologically no LNI (pN0). Outcomes of the study were cancer-specific mortality (CSM) and other-cause mortality. Multivariable competing-risks regression models assessed the impact of inflammatory lymphadenopathies (cN1pN0) on mortality rates, after adjustment for clinical and pathological confounders., Results: 114 (16%) and 605 (84%) patients (16%) were cN1pN0 and cN0pN0, respectively. cN1pN0 patients were more frequently diagnosed with larger tumours (8.4 vs. 6.5 cm), higher pathological tumour stage (pT3-4 in 71 vs. 36%), higher Fuhrman grade (G3-G4 in 64 vs. 31%), more frequently with necrosis (75 vs. 44%), and distant metastases (33 vs. 10%) (all p < 0.0001). At univariable analysis, inflammatory lymphadenopathies resulted associated with worse CSM (HR 2.45; p < 0.0001). However, at multivariable analysis, inflammatory lymphadenopathies were not an independent predictor of CSM (HR 0.81; p = 0.4). The presence of metastases at diagnosis was the most important factor affecting CSM (HR 6.54; p < 0.0001). This study is limited by its retrospective nature., Conclusions: In RCC patients, inflammatory lymphadenopathies (cN1pN0) are associated with unfavourable clinical and pathological characteristics. However, the presence of inflammatory lymphadenopathies does not affect RCC-specific mortality.

Background: The role of lymph node dissection (LND) during nephrectomy for renal cell carcinoma (RCC) is controversial. We looked at the clinical usefulness of performing LND to stratify the risk of patients with RCC and select candidates for systemic treatment after nephrectomy., Materials and Methods: We identified 730 patients with nonmetastatic RCC treated with nephrectomy and LND at a single center. We compared the accuracy and clinical usefulness of a base model including factors defining high-risk patients according to the S-TRAC trial [(pT3 and Grade≥2 and performance status score ≥1) or pT4] relative to the base model plus pN stage for the prediction of early progression after surgery., Results: LN invasion resulted the most informative predictor of early progression (odds ratio: 6.39; 95% confidence interval [CI]: 3.26, 12.54; P < 0.0001). The accuracy was higher (P = 0.008) for the model implemented with pN (area under the curve: 0.76; 95% CI: 0.71, 0.80) as compared to the base model (area under the curve: 0.72; 95% CI: 0.68, 0.76). Performing LND to select patients for postoperative systemic treatment, resulted in a slightly higher net benefit as compared to a strategy defining risk on the base of factors other than pN. Patients with high-risk disease showed a large difference in the risk of progression according to pN-status (1-year risk: 58% [95% CI: 45, 72] for pN1; 31% [95% CI: 25, 38] for pN0; P < 0.001)., Conclusions: Performing LND at the time of nephrectomy improves risk stratification, resulting into a small but nonnegligible clinical advantage for selecting high-risk patients for further treatment after surgery. Further trials should investigate whether high-risk pN1 patients would benefit from a different postoperative management., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The hypothesis that renal function could influence oncological outcomes is supported by anecdotal literature., Objective: To determine whether estimated glomerular filtration rate (eGFR) is related to cancer-specific mortality (CSM) in patients who had undergone surgery for renal cell carcinoma (RCC)., Design, Setting, and Participants: A retrospective analysis of 3457 patients who underwent radical (39%) or partial nephrectomy (61%) for cT1-2 RCC between 1990 and 2015., Outcome Measurements and Statistical Analysis: The eGFR was calculated by the Chronic Kidney Disease Epidemiology Collaboration equation. CSM was analyzed in a multivariable competing-risk framework, estimating the subdistribution hazard ratio (SHR) accounting for deaths from other causes. The relationship between eGFR and CSM was investigated from multiple statistical approaches-extended Cox regression with eGFR incorporated as a time-dependent covariate, landmark analysis, and joint modeling. Other predictors were selected by competing-risk random forest method and backward elimination., Results and Limitations: The relationship between eGFR and CSM was graphically described by a linear spline, i.e. a continuous piecewise linear function with two lines joined by a knot. For eGFR treated as a time-dependent covariate, the knot was located at 65ml/min; at landmark analysis with eGFR at the baseline, 12 mo, and last functional follow-up, the knots were 85, 60, and 65ml/min, respectively. In multivariable competing-risk analysis, CSM was associated with eGFR only for values of eGFR below these cutoffs, with SHRs for every 10ml/min of reduction in eGFR of 1.25 (p=0.003), 1.16 (p=0.028), 1.44 (p=0.02), and 1.16 (p=0.042), corresponding to time-dependent eGFR, and eGFR at baseline, 12 mo, and last functional follow-up, respectively. Joint modeling confirmed these results. A retrospective design with inherent biases in data collection represents a limitation., Conclusions: In patients undergoing surgery for RCC, renal function should be preserved in order to improve cancer-related survival., Patient Summary: The relationship between renal function and probability of dying due to renal cancer is complex. The present study found a correlation between glomerular filtration rate and cancer specific mortality that could reconsider the oncological role of renal function in patients undergoing surgery for renal cancer., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: Primary renal liposarcoma is an unusual malignant mesenchymal tumor. In this context, all the previous reports were based on cases with insufficient data regarding the natural history of the disease. We decided to fill this gap, reporting the largest single institution series of patients with primary RL and a review of the already available literature., Methods: We describe 3 cases with radiologically and histologically-confirmed RL out of 3,224 surgeries performed for primary kidney cancers over 28 years (1987-2015, 0.09%) at a single tertiary care center., Results: Patients underwent open radical nephrectomy with an anterior transperitoneal access with complete resection of the retroperitoneal mass and retroperitoneal lymph node dissection; all patients died from tumor progression after a mean time of 45 months., Conclusions: In conclusion, RL is a very rare mesenchymal renal tumor, with sporadic cases reported. We reported the largest case series of primary RL. The most appropriate approach for RL is nephrectomy with complete resection of all the neoplastic tissue. Stringent follow-up scheme is required due to a high rate of disease recurrence and progression. The role of adjuvant and salvage therapy remains to be investigated.

Background/aim: The incidence of renal cell carcinoma (RCC) has been increasing mainly due to the increase in the incidental detection of small renal masses. The aim of this study was to verify whether the trend towards early diagnosis changed the clinical characteristics of pathologically-defined high-risk RCC patients over the last decades., Patients and Methods: A total of 741 patients with pathologically-confirmed high-risk RCC (pT1-4, and/or pN1 and/or Fuhrman grade 3-4 and/or all M1 patients) treated with radical (RN) or partial nephrectomy (PN) at a single tertiary referral center between 1987 and 2011 were included in the study. The temporal trends of pre-operative clinical and tumor characteristics were assessed relying on the lowess smoother weighted function with corresponding 95% confidence interval. Estimated annual percentage changes (EAPC) were evaluated using a log linear regression model., Results: The median age of patients increased from 57.5 to 67.3 years between 1987 and 2011 (EAPC 4.9%, p=0.002). Body mass index and gender rates remained stable during the study period. A constant trend towards patients with one or more comorbidity was observed. Moreover, the proportion of asymptomatic patients at diagnosis and of clinical T1 increased by 41.1 and 19.8%, respectively (all p≤0.007). The clinical tumor size dropped from 8.4 to 6.2 cm (EAPC -1.2%, p=0.001). This trend was accompanied by a clinically-relevant increase by 15.3% in the rate of patients without clinical metastases (p=0.07). Conversely, the rate of clinical lymphadenopathies remained stable over time. Finally, the rate of PNs performed increased by 23.3% (p<0.001)., Conclusion: Over the years, pathologically-confirmed high-risk RCC patients are older, mostly asymptomatic, with smaller cancers, with a higher rate of tumors localized to the kidney and with a decreased rate of metastatic disease at diagnosis. These trends can explain the increasing number of PNs performed despite the presence of a high-risk cancer profile., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: We assessed the accuracy of the UISS (UCLA Integrated Staging System) to predict the postoperative recurrence of renal cell carcinoma. We also evaluated whether including patient age and tumor histology would improve clinical decision making., Materials and Methods: We analyzed the records of 1,630 patients treated with nephrectomy at a single academic center. The accuracy of the UISS model to predict early (12 months or less) and late (more than 60 months) recurrence after surgery was compared with a new model including patient age and disease histology., Results: The new model and the UISS model showed high accuracy to predict early recurrence after surgery (AUC 0.84, 95% CI 0.81-0.88 and 0.83, 95% CI 0.80-0.87, respectively). In patients diagnosed with low risk tumor types (eg papillary type 1 and chromophobe lesions) the average risk of early recurrence significantly decreased in each UISS risk category when tumor histology was added to the predictive model (low risk 1.6% vs 0.6%, intermediate risk 5.5% vs 1.9% and high risk 45% vs 22%). Kaplan-Meier analysis showed no difference in the risk of late recurrence among the UISS risk categories., Conclusions: The UISS model should be applied to tailor the early followup protocol after nephrectomy. Patients with low risk histology deserve less stringent followup regardless of the UISS risk category. Our results do not support a risk stratification model to design a surveillance protocol after 5 years postoperatively., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Lymph node dissection may benefit patients at increased risk for lymph node metastases from renal cell carcinoma. Therefore, we evaluated the association of lymph node dissection with survival in patients at high risk undergoing radical nephrectomy for renal cell carcinoma., Materials and Methods: We identified 2,722 patients with M0 renal cell carcinoma who underwent radical nephrectomy with or without lymph node dissection at 2 international centers from 1990 to 2010. The associations of lymph node dissection with the development of distant metastases, and cancer specific and all cause mortality were evaluated using propensity score techniques and traditional multivariable Cox regression. Subset analyses were done to examine patients at increased risk of lymph node metastases., Results: Overall 171 patients (6.3%) had pN1 disease. Median followup was 9.6 years. Clinicopathological features were well balanced after propensity score adjustment. Lymph node dissection was not significantly associated with a reduced risk of distant metastases, or cancer specific or all cause mortality in the overall cohort, among patients with preoperative radiographic lymphadenopathy (cN1), or across an increasing probability of pN1 disease from 0.10 or greater to 0.50 or greater. Neither extended lymph node dissection nor the extent of lymph node dissection was associated with improved oncologic outcomes., Conclusions: The current analysis of a large, international cohort indicates that lymph node dissection is not associated with improved oncologic outcomes among patients at high risk who undergo radical nephrectomy for M0 renal cell carcinoma. This includes patients with radiographic lymphadenopathy (cN1) and across increasing probability thresholds of pN1 disease., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)