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Purpose: There is sparse evidence on outcomes of resected occult LN metastases at the time of nephrectomy (synchronous disease). We sought to analyse a large international cohort of patients and to identify clinico-pathological predictors of long-term survival., Materials and Methods: We collected data of consecutive patients who underwent nephrectomy and LND for T any cN0-1pN1 and cM0-1 RCC at 7 referral centres between 1988 and 2019. Patients were stratified into four clinico-pathological groups: (1) cN0cM0-pN1, (2) cN1cM0-pN1(limited, 1-3 positive nodes), (3) cN1cM0-pN1(extensive, > 3 positive nodes), and (4) cM1-pN1. Overall survival (OS) was estimated using the Kaplan-Meier method, and associations with all-cause mortality (ACM) were evaluated using Cox models with multiple imputations., Results: Of the 4370 patients with LND, 292 patients with pN1 disease were analysed. Median follow-up was 62 months, during which 171 patients died. Median OS was 21 months (95% CI 17-30 months) and the 5-year OS rate was 24% (95% CI 18-31%). Patients with cN0cM0-pN1 disease had a median OS of 57 months and a 5-year OS rate of 43%. 5-year OS (median OS) decreased to 29% (33 months) in cN1cM0-pN1(limited) and to 23% (23 months) in cN1cM0-pN1(extensive) patients. Those with cM1-pN1 disease had the worst prognosis, with a 5-year OS rate of 13% (9 months). On multivariable analysis, age (p = 0.034), tumour size (p = 0.02), grade (p = 0.02) and clinico-pathological group (p < 0.05) were significant predictors of ACM., Conclusion: Depending on clinico-pathological group, grade and tumour size, 5-year survival of patients with LN metastases varies from 13 to 43%. Patients with resected occult lymph node involvement (cN0/pN1 cM0) have the best prognosis with a considerable chance of long-term survival., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Objective: To investigate whether pT1 renal cell carcinoma (RCC) should be followed differently after partial (PN) or radical nephrectomy (RN) based on a retrospective analysis of a multicentre database (RECUR)., Subjects: A retrospective study was conducted in 3380 patients treated for nonmetastatic RCC between January 2006 and December 2011 across 15 centres from 10 countries, as part of the RECUR database project. For patients with pT1 clear-cell RCC, patterns of recurrence were compared between RN and PN according to recurrence site. Univariate and multivariate models were used to evaluate the association between surgical approach and recurrence-free survival (RFS) and cancer-specific mortality (CSM)., Results: From the database 1995 patients were identified as low-risk patients (pT1, pN0, pNx), of whom 1055 (52.9%) underwent PN. On multivariate analysis, features associated with worse RFS included tumour size (hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.14-1.39; P < 0.001), nuclear grade (HR 2.31, 95% CI 1.73-3.08; P < 0.001), tumour necrosis (HR 1.5, 95% CI 1.03-2.3; P = 0.037), vascular invasion (HR 2.4, 95% CI 1.3-4.4; P = 0.005) and positive surgical margins (HR 4.4, 95% CI 2.3-8.5; P < 0.001). Kaplan-Meier analysis of CSM revealed that the survival of patients with recurrence after PN was significantly better than those with recurrence after RN (P = 0.02). While the above-mentioned risk factors were associated with prognosis, type of surgery alone was not an independent prognostic variable for RFS nor CSM. Limitations include the retrospective nature of the study., Conclusion: Our results showed that follow-up protocols should not rely solely on stage and type of primary surgery. An optimized regimen should also include validated risk factors rather than type of surgery alone to select the best imaging method and to avoid unnecessary imaging. A follow-up of more than 3 years should be considered in patients with pT1 tumours after RN. A novel follow-up strategy is proposed., (© 2021 The Authors BJU International © 2021 BJU International Published by John Wiley & Sons Ltd.)

Purpose: To investigate the natural history and follow-up after kidney tumor treatment of Von Hippel-Lindau (VHL) patients., Materials and Methods: A multi-institutional European consortium of patients with VHL syndrome included 96 non-metastatic patients treated at 9 urological departments (1987-2018). Descriptive and survival analyses were performed., Results and Limitations: Median age at VHL diagnosis was 34 years (IQR 25-43). Two patients (2.1%) showed only renal manifestations at VHL diagnosis. Concomitant involvement of Central Nervous System (CNS) vs. pancreas vs. eyes vs. adrenal gland vs. others were present in 60.4 vs. 68.7 vs. 30.2 vs. 15.6 vs. 15.6% of patients, respectively. 45% of patients had both CNS and pancreatic diseases alongside kidney. The median interval between VHL diagnosis and renal cancer treatment resulted 79 months (IQR 0-132), and median index tumor size leading to treatment was 35.5 mm (IQR 28-60). Of resected malignant tumours, 73% were low grade. Of high-grade tumors, 61.1% were large > 4 cm. With a median follow-up of 8 years, clinical renal progression rate was 11.7% and 29.3% at 5 and 10 years, respectively. Overall mortality was 4% and 7.5% at 5 and 10 years, respectively. During the follow-up, 50% of patients did not receive a second active renal treatment. Finally, 25.3% of patients had CKD at last follow-up., Conclusions: Mean period between VHL diagnosis and renal cancer detection is roughly three years, with significant variability. Although, most renal tumors are small low-grade, clinical progression and mortality are not negligible. Moreover, kidney function represents a key issue in VHL patients., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Background: Cancer du Rein Métastatique Nephrectomie et Antiangiogéniques (CARMENA) concluded that sunitinib alone is not inferior to cytoreductive nephrectomy (CN) followed by vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) in patients with metastatic renal cell carcinoma. It remains uncertain whether deferred CN is beneficial in this setting., Objective: The aim of this study was to compare outcome in patients treated with presurgical VEGFR-TKI followed by CN (deferred CN) with that in patients receiving CN followed by VEGFR-TKI (upfront CN)., Design, Setting, and Participants: Pooled data from prospective trials in which a strategy of deferred CN in the absence of disease progression was investigated were compared with a retrospective dataset of upfront CN., Outcome Measurements and Statistical Analysis: Overall survival (OS) in the Memorial Sloan-Kettering Cancer Center (MSKCC) intermediate-risk group., Results and Limitations: Patients were treated between 2006 and 2016. In the MSKCC intermediate-risk group, 144 patients with a strategy of deferred CN after systemic therapy were compared with 131 patients treated with upfront CN. OS in the deferred cohort was 33.0 mo (95% confidence interval [CI] 25.0-51.0) compared with 22.8 mo (95% CI 17.9-30.6) after upfront CN (hazard ratio 0.72 [95% CI 0.52-0.996], p = 0.047). This study is limited by retrospective comparison of data, subgroup analysis, and a lack of intention-to-treat data for the upfront CN cohort., Conclusions: In MSKCC intermediate-risk patients, a strategy of deferred CN in the absence of progression yields OS, which compares favourably with upfront CN and published trial data from CARMENA. This warrants a formal individual patient data analysis of CARMENA, SURTIME, and single-arm prospective studies to define the role and timing of deferred CN in intermediate-risk patients., Patient Summary: In this study, we report outcomes in patients with metastatic renal cell cancer treated with targeted therapy followed by nephrectomy, which compared favourably with nephrectomy followed by targeted therapy and results from published studies., (Copyright © 2020. Published by Elsevier B.V.)

Purpose: The impact of resection technique on partial nephrectomy outcomes is controversial. The aim of this study was to evaluate the pattern of resection techniques during partial nephrectomy and the impact on perioperative outcomes, acute kidney injury, positive surgical margins and the achievement of the Trifecta (negative surgical margins, no perioperative Clavien-Dindo grade 2 or greater surgical complications and no postoperative acute kidney injury)., Materials and Methods: We prospectively collected data on consecutive patients with cT1-2N0M0 renal masses treated with partial nephrectomy at a total of 16 referral centers from September 2014 to March 2015. After partial nephrectomy the resection technique was classified by the surgeon as enucleation, enucleoresection or resection according to the SIB (Surface-Intermediate-Base) margin scores 0 to 2, 3 or 4 and 5, respectively. Multivariable logistic regression analysis was done to evaluate the potential impact of the resection technique on postoperative surgical complications, positive surgical margins, acute kidney injury and Trifecta achievement., Results: Overall 507 patients were included in analysis. The resection technique was classified as enucleation in 266 patients (52%), enucleoresection in 150 (30%) and resection in 91 (18%). The resection technique (enucleoresection vs enucleation and resection) was the only significant predictor of positive surgical margins. Tumor complexity, surgical approach (open and laparoscopic vs robotic) and resection technique (enucleoresection vs enucleation) were significant predictors of Clavien-Dindo grade 2 or greater surgical complications. The surgical approach (open and laparoscopic vs robotic), the resection technique (enucleoresection vs enucleation) and warm ischemia time were significantly associated with postoperative acute kidney injury and Trifecta achievement., Conclusions: Resection techniques significantly impact surgical complications, early functional outcomes and positive surgical margins after partial nephrectomy of localized renal masses.

Despite the important relationship between renorrhaphy and functional outcomes of partial nephrectomy, the urological guidelines do not provide recommendations about the optimal renorrhaphy technique. We carried out the first pooled literature analysis of the impact of suture technique on ultimate renal function after partial nephrectomy. Three studies comparing interrupted versus running suture including data on glomerular filtration rate (GFR) were included, for a total of 124 versus 269 patients. No significant differences were found between pre- and postoperative GFR in either patients who received an interrupted suture (weighted mean difference, -4.88ml/min, 95% confidence interval [CI] -11.38; 1.63, p=0.14) or those who received a running suture (-3.42ml/min, 95% CI -9.96; 3.12, p=0.31). Three studies comparing single- versus double-layer renorrhaphy included data on GFR (321 vs 199 patients). A benefit in functional outcomes favored single-layer technique (-3.19ml/min, 95% CI -8.09; 1.70, p=0.2 vs -6.07ml/min, 95% CI -10.75; -1.39, p=0.01). In conclusion, our quantitative synthesis suggests a renal functional benefit of the single-layer closure during partial nephrectomy. PATIENT SUMMARY: The available studies on renal functional data included in the present review suggest that "less is more" for renorrhaphy after partial nephrectomy. The single-layer renorrhaphy technique showed advantages in renal functional outcomes compared with the double-layer technique., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To summarize the available evidence on renorrhaphy techniques and to assess their impact on peri-operative outcomes after minimally invasive partial nephrectomy (MIPN)., Materials and Methods: A systematic review of the literature was performed in January 2018 without time restrictions, using MEDLINE, Cochrane and Web of Science databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement recommendations. Studies providing sufficient details on renorrhaphy techniques during laparoscopic or robot-assisted partial nephrectomy and comparative studies focused on peri-operative outcomes were included in qualitative and quantitative analyses, respectively., Results: Overall, 67 and 19 studies were included in the qualitative and quantitative analyses, respectively. The overall quality of evidence was low. Specific tumour features (i.e. size, hilar location, anatomical complexity, nearness to renal sinus and/or urinary collecting system), surgeon's experience, robot-assisted technology, as well as the aim of reducing warm ischaemia time and the amount of devascularized renal parenchyma preserved represented the key factors driving the evolution of the renorrhaphy techniques during MIPN over the past decade. Quantitative synthesis showed that running suture was associated with shorter operating and ischaemia time, and lower postoperative complication and transfusion rates than interrupted suture. Barbed suture had lower operating and ischaemia time and less blood loss than non-barbed suture. The single-layer suture technique was associated with shorter operating and ischaemia time than the double-layer technique. No comparisons were possible concerning renal functional outcomes because of non-homogeneous data reporting., Conclusions: Renorrhaphy techniques significantly evolved over the years, improving outcomes. Running suture, particularly using barbed wires, shortened the operating and ischaemia times. A further advantage could derive from avoiding a double-layer suture., (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)

Introduction: Recent trials have emphasized the importance of a precise patient selection for cytoreductive nephrectomy (CN). In 2013, a nomogram was developed for pre- and postoperative prediction of the probability of death (PoD) after CN in patients with metastatic renal cell carcinoma. To date, the single-institutional nomogram which included mostly patients from the cytokine era has not been externally validated. Our objective is to validate the predictive model in contemporary patients in the targeted therapy era., Methods: Multi-institutional European and North American data from patients who underwent CN between 2006 and 2013 were used for external validation. Variables evaluated included preoperative serum albumin and lactate dehydrogenase levels, intraoperative blood transfusions (yes/no) and postoperative pathologic stage (primary tumour and nodes). In addition, patient characteristics and MSKCC risk factors were collected. Using the original calibration indices and quantiles of the distribution of predictions, Kaplan-Meier estimates and calibration plots of observed versus predicted PoD were calculated. For the preoperative model a decision curve analysis (DCA) was performed., Results: Of 1108 patients [median OS of 27 months (95% CI 24.6-29.4)], 536 and 469 patients had full data for the validation of the pre- and postoperative models, respectively. The AUC for the pre- and postoperative model was 0.68 (95% CI 0.62-0.74) and 0.73 (95% CI 0.68-0.78), respectively. In the DCA the preoperative model performs well within threshold survival probabilities of 20-50%. Most important limitation was the retrospective collection of this external validation dataset., Conclusions: In this external validation, the pre- and postoperative nomograms predicting PoD following CN were well calibrated. Although performance of the preoperative nomogram was lower than in the internal validation, it retains the ability to predict early death after CN.

Background: A non-negligible proportion of individuals diagnosed with cT1 renal cell carcinoma (RCC) are upstaged to pT3a at final pathology. Few data on oncological outcomes for these patients are available to determine whether partial nephrectomy (PN) might jeopardise cancer control., Objective: To assess, within an international multi-institutional collaboration, whether PN might undermine cancer control relative to radical nephrectomy (RN) in RCC patients with unexpected pT3a disease., Design, Setting, and Participants: International multi-institutional collaboration including patients with cT1abN0M0-pT3a RCC., Intervention: PN or RN., Outcome Measurements and Statistical Analysis: We used Kaplan-Meier analyses, before and after propensity-score matching, to evaluate differences in metastatic progression (MP) and cancer-specific mortality (CSM) rates during follow-up. Univariable and multivariable Cox regression analyses were used to assess predictors of MP and CSM., Results and Limitations: Overall, 309 patients with cT1abN0M0 RCC (cT1aN0M0, n=107, 34.6%; cT1bN0M0, n=202, 65.4%) had pT3a disease according to final pathology. Patients were treated with either PN (n=71, 23%) or RN (n=238, 77%). MP at 1, 2, and 5 yr was detected in 9.1%, 13.3%, and 24.1% of patients, respectively. CSM was 3.5%, 10.7%, and 18.4% at 1, 2, and 5 yr, respectively. After matching, no difference in terms of MP or CSM was observed between the PN and RN cohorts (both p>0.3). On multivariable analysis, type of surgery (PN vs RN) was not an independent predictor of either MP (p=0.3) or CSM (p=0.4). Limitations include the retrospective design., Conclusions: In patients with unexpected pT3a RCC at final pathology, PN does not appear to jeopardise cancer control with regard to MP and CSM., Patient Summary: Cancer control is similar between patients treated with removal of the entire kidney and those with only partial removal, even if the final histology examination demonstrates a tumour that is unexpectedly not confined within the kidney., (Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Context: Nephron-sparing approaches are increasingly recommended for incidental small renal masses. Herein, we review the current literature regarding the safety and efficacy of focal therapy, including percutaneous ablation, for small renal masses., Objective: To summarize the application of ablative therapy in the management of small renal masses., Evidence Acquisition: PubMed and Medline database search was performed to look for findings published since 2000 on focal therapy for small renal masses. After literature review, 64 articles were selected and discussed., Evidence Synthesis: Radiofrequency ablation and cryotherapy are the most widely used procedures with intermediate-term oncological outcome comparable with surgical series. Cost effectiveness seems excellent and side effects appear acceptable. To date, no randomized trial comparing percutaneous focal therapy with standard surgical approach or active surveillance has been performed., Conclusions: Focal ablative therapies are now accepted as effective treatment for small renal tumors. For tumors <3cm, oncological effectiveness of ablative therapies is comparable with that of partial nephrectomy. Percutaneous ablation has fewer complications and a better postoperative profile when compared with minimally invasive partial nephrectomy., Patient Summary: Focal ablative therapies are now accepted as effective treatment for small renal tumors. For tumors <3cm, oncological effectiveness of ablative therapies is comparable with that of partial nephrectomy., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: To test the hypothesis that cytoreductive nephrectomy (CN) improves overall survival (OS) of patients with synchronous metastatic renal cell carcinoma (mRCC), who subsequently receive targeted therapies (TT)., Methods: We identified 261 patients who received TT for synchronous mRCC with or without prior CN. To achieve balance in baseline characteristics between groups, we used the inverse probability of treatment weighting (IPTW) method. We conducted OS analyses, including IPTW-adjusted Kaplan-Meier curves, Cox regression models, interaction term, and landmark and sensitivity analyses., Results: Of the 261 patients, 97 (37.2%) received CN and 164 (62.8%) did not. IPTW-adjusted analyses showed a statistically significant OS benefit for patients treated with CN (HR 0.63, 95% CI 0.46-0.83, P = 0.0015). While there was no statistically significant difference in OS at 3 months (P = 0.97), 6 months (P = 0.67), and 12 months (P = 0.11) from diagnosis, a benefit for the CN group was noted at 18 months (P = 0.005) and 24 months (P = 0.004). On interaction term analyses, the beneficial effect of CN increased with better performance status (P = 0.06), in women (P = 0.03), and in patients with thrombocytosis (P = 0.01)., Conclusions: IPTW-adjusted analysis of our patient cohort suggests that CN improves OS of patients with synchronous mRCC treated with TT. On the whole, the survival difference appears after 12 months. Specific subgroups may particularly benefit from CN, and these subgroups warrant further investigation in prospective trials.

Objective: To validate microvascular (MVI) and lymphovascular (LVI) invasion as prognostic factors in patients with renal cell carcinoma (RCC)., Patients and Methods: Data of patients with RCC who underwent radical or nephron-sparing surgery were prospectively collected from three academic centres. The occurrence of MVI and LVI was determined with standard staining protocols by experienced pathologists at the time of diagnosis. The association of MVI and LVI with clinicopathological data, metastatic spread, and cancer-specific survival (CSS) were evaluated with Fisher's exact tests, binary logistic regression analyses, and univariable and multivariable Cox proportional hazard regression models., Results: MVI was present in 201 of 747 patients (26.9%) and was associated with advanced Tumour-Node-Metastasis (TNM) stages, high Fuhrman grades, and sarcomatoid features (all P < 0.001). MVI was associated with a higher rate of metastatic spread. LVI was present in 32 of 573 patients (5.5%) and was associated with advanced TNM stages, high Fuhrman grade, and sarcomatoid features (all P < 0.001). Two-thirds of LVI-positive patients died (P < 0.001). Both LVI and MVI were significantly associated with CSS in all patients, clear cell RCC (ccRCC), and localised RCC in univariable analysis (all P < 0.001). On multivariable analysis, presence of MVI was identified as an independent prognostic factor (hazard ratio 2.09; P = 0.001). Moreover, MVI [odds ratio (OR) 2.7; P = 0.001] and not macrovascular invasion (P = 0.895) was an independent predictor of sychronuous metastatic spread. LVI was the strongest factor associated with sychronous metastatic spread (OR 4.73, 95% confidence interval 1.84-12.14; P = 0.001) in all patients and in the subgroup of patients with ccRCC (P = 0.001)., Conclusions: The present study validated LVI and MVI as prognostic factors for poor outcome in RCC. These findings endorse an evaluation of both variables in the clinical routine setting to facilitate survival prognostication in follow-up protocols and for assignment to adjuvant treatment trials., (© 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.)

Objective: To analyze the impact of gender on the clinicopathologic features and survival of patients with surgically treated papillary renal cell carcinoma (papRCC) using a comprehensive international multicenter database., Materials and Methods: Data of 2325 patients undergoing surgery for unilateral papRCC between 1984 and 2015 in 17 European and North American centers were retrospectively collated. The impact of clinicopathologic features on the likelihood of nephron-sparing surgery (NSS) was evaluated using a multivariable logistic regression model. The influence on cancer-specific mortality (CSM) and other-cause mortality was analyzed by multivariable competing-risk regression models. Finally, subgroup analyses were conducted for organ-confined (n = 2075) and non-organ-confined tumors (n = 250). The median follow-up was 47 months., Results: The study cohort included 1782 (77%) male patients (male-to-female ratio 3.3:1.0). Considering age, symptoms at presentation, performance status, pathologic tumor size, stage, and grade, we observed that there were no significant gender-specific differences. In contrast, female patients underwent NSS significantly less frequently (P <.001). On multivariable analysis, the likelihood of NSS was 72% higher in male patients after adjusting for all relevant cofactors (P <.001). No significant gender-specific differences in terms of CSM and other-cause mortality were demonstrated, but CSM was 59% lower in female patients in the subgroup of organ-confined tumors (P = .001)., Conclusion: No impact of gender on survival was found analyzing this large cohort of patients undergoing surgery for papRCC. However, CSM appears to be lower in female patients with organ-confined disease. In this context, it is interesting that the likelihood of NSS seems to be significantly higher in male patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: To construct a nomogram based on preoperative variables to better predict the likelihood of complications occurring within 30 days of radical nephroureterectomy (RNU)., Patients and Methods: The charts of 731 patients undergoing RNU at eight academic medical centres between 2002 and 2014 were reviewed. Preoperative clinical, demographic and comorbidity indices were collected. Complications occurring within 30 days of surgery were graded using the modified Clavien-Dindo scale. Multivariate logistic regression determined the association between preoperative variables and post-RNU complications. A nomogram was created from the reduced multivariate model with internal validation using the bootstrapping technique with 200 repetitions., Results: A total of 408 men and 323 women with a median age of 70 years and a body mass index of 27 kg/m 2 were included. A total of 75% of the cohort was white, 18% had an Eastern Cooperative Oncology Group (ECOG) performance status ≥2, 20% had a Charlson comorbidity index (CCI) score >5 and 50% had baseline chronic kidney disease (CKD) ≥ stage III. Overall, 279 patients (38%) experienced a complication, including 61 events (22%) with Clavien grade ≥ III. A multivariate model identified five variables associated with complications, including patient age, race, ECOG performance status, CKD stage and CCI score. A preoperative nomogram incorporating these risk factors was constructed with an area under curve of 72.2%., Conclusions: Using standard preoperative variables from this multi-institutional RNU experience, we constructed and validated a nomogram for predicting peri-operative complications after RNU. Such information may permit more accurate risk stratification on an individual cases basis before major surgery., (© 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.)

Objective: To assess the association of smoking status with standard clinicopathological features and overall survival (OS) in a large multi-institutional cohort of patients with metastatic renal cell carcinoma (mRCC) treated with cytoreductive nephrectomy (CNT)., Methods: A total of 613 patients with mRCC treated with CNT in US and Europe institutions between 1990 and 2013 were included. Smoking history comprised smoking status, smoking duration in years, number of cigarettes per day and years since smoking cessation. Cumulative smoking exposure was categorized as light short term, heavy long term and moderate. Association between smoking history and OS was assessed by Cox regression logistic analysis., Results: One hundred and seventy-one patients (27.9 %) never smoked, 193 (31.5 %) were former smokers and 249 (40.6 %) were current smokers. Smoking status was associated with a higher number of metastases (p < 0.001) and an abnormal preoperative corrected calcium level (p = 0.01). Median follow-up was 16 (IQR 7-24) months. Current smokers had a shorter OS than never and former smokers (log rank, p = 0.004). Smoking status was significantly associated with OS in univariable analysis (HR 1.45; 95 % CI 1.16-1.82; p < 0.001), and in multivariable analysis that adjusted for established prognostic factors (HR 1.46; 95 % CI 1.16-1.84; p = 0.002). Daily consumption of more than 20 cigarettes, more than 20 years of smoking exposure and heavy long exposure were all independent prognosticators of worse OS., Conclusions: Current smoking and a higher cumulative smoking exposure are associated with a higher risk of death in patients with mRCC treated with CNT. Even at this stage, smoking negatively affects kidney cancer outcomes.

Background: Excision repair cross-complementing 1 (ERCC1) has been associated with outcomes of urothelial carcinoma of the bladder, but was not yet studied in upper tract urothelial carcinoma (UTUC). The aim of this study was to assess the prognostic role of ERCC1 expression in a large international cohort of UTUC patients., Methods: Immunohistochemical ERCC1 expression was evaluated in 716 UTUC patients who underwent radical nephroureterectomy with curative intent. ERCC1 was considered positive when the H-score was >1.0. Associations with overall survival and cancer-specific survival were assessed using univariable and multivariable Cox models., Results: ERCC1 was expressed in 303 tumors (42.3 %) and linked with the presence of tumor necrosis (16.2 vs. 10.4 %, p = 0.023), but not with any other clinical or pathological variable. ERCC1 status did not predict cancer-specific survival and overall survival on both univariable (p = 0.70 and 0.32, respectively) and multivariable analyses (p = 0.48 and 0.33, respectively)., Conclusions: ERCC1 is expressed in a significant proportion of UTUC and is linked with tumor necrosis, but its expression appears not to be associated with prognosis following radical nephroureterectomy.

Purpose: We compared the oncologic outcomes of radical nephroureterectomy, distal ureterectomy and endoscopic surgery for elective treatment of clinically organ confined upper tract urothelial carcinoma of the distal ureter., Materials and Methods: From a multi-institutional collaborative database we identified 304 patients with unifocal, clinically organ confined urothelial carcinoma of the distal ureter and bilateral functional kidneys. Rates of overall, cancer specific, local recurrence-free and intravesical recurrence-free survival according to surgery type were compared using Kaplan-Meier statistics. Univariable and multivariable Cox regression analyses were performed to assess the adjusted outcomes of radical nephroureterectomy, distal ureterectomy and endoscopic surgery., Results: Overall 128 (42.1%), 134 (44.1%) and 42 patients (13.8%) were treated with radical nephroureterectomy, distal ureterectomy and endoscopic surgery, respectively. Although rates of overall, cancer specific and intravesical recurrence-free survival were equivalent among the 3 surgical procedures, 5-year local recurrence-free survival was lower for endoscopic surgery (35.7%) than for nephroureterectomy (95.0%, p <0.001) or ureterectomy (85.5%, p = 0.01) with no significant difference between nephroureterectomy and distal ureterectomy. On multivariable analyses only endoscopic surgery was an independent predictor of decreased local recurrence-free survival compared to nephroureterectomy (HR 1.27, p = 0.001) or distal ureterectomy (HR 1.14, p = 0.01). Distal ureterectomy and endoscopic surgery did not significantly correlate to cancer specific or intravesical recurrence-free survival. However, when adjustment was made for ASA(®) (American Society of Anesthesiologists(®)) score, distal ureterectomy (HR 0.80, p = 0.01) and endoscopic surgery (HR 0.84, p = 0.02) were independent predictors of increased overall survival, although no significant difference was found between them., Conclusions: Because of better oncologic outcomes, distal ureterectomy could be considered the elective first line treatment of clinically organ confined urothelial carcinoma of the distal ureter., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the efficacy and technical applicability of cavitron ultrasonic surgical aspirator (CUSA)-driven zero-ischemia open partial nephrectomy in patients with renal tumors., Materials and Methods: We prospectively collected data of 13 consecutive patients, who underwent open partial nephrectomy under non-ischemic conditions. Tumor resection was done using an ultrasonic device (CUSA/SONOCA 300). Demographic and laboratory data, tumor characteristics, perioperative, and postoperative variables were evaluated., Results: The median age was 60.0 years (range 40-76); body mass index 28.0 kg/m(2) (range 22.9-43.3); tumor size 37.0 mm (range 11-110 mm). Patient were stratified according to the PADUA score into low- (score 6-7; n - 4), intermediate- (score 8-9; n - 5), and high-risk (score of >10; n - 4) groups, and the median score was 9.0 (range 6-13; SD +2.3). The vast majority of kidney tumors were diagnosed incidentally (n - 11; 84.6 %). Median operative time was 175 min (55-270 min); median time of tumor extirpation was 12 min (6-25 min); and median blood loss was 250 ml. Serum creatinine, glomerular filtration rate, and hemoglobin were nearly unaltered before and after surgery in 11 cases (84.6 %). Three patients received a blood transfusion (Clavien-Dindo Grade II); one had Grade IIIa complication (insertion of double J stent without general anesthesia); and three had Grade IIIb complications (insertion of double J under general anesthesia)., Conclusions: The ultrasonic device demonstrated acceptable hemostatic and resection properties during open partial nephrectomy without ischemia. Our series showed promising perioperative and postoperative outcomes that may help in maximizing preservation of renal function in partial nephrectomy candidates.

Purpose: Pretreatment measurements of systemic inflammatory response, including the Glasgow prognostic score (GPS), the neutrophil-to-lymphocyte ratio (NLR), the monocyte-to-lymphocyte ratio (MLR), the platelet-to-lymphocyte ratio (PLR) and the prognostic nutritional index (PNI) have been recognized as prognostic factors in clear cell renal cell carcinoma (CCRCC), but there is at present no study that compared these markers., Methods: We evaluated the pretreatment GPS, NLR, MLR, PLR and PNI in 430 patients, who underwent surgery for clinically localized CCRCC (pT1-3N0M0). Associations with disease-free survival were assessed with Cox models. Discrimination was measured with the C-index, and a decision curve analysis was used to evaluate the clinical net benefit., Results: On multivariable analyses, all measures of systemic inflammatory response were significant prognostic factors. The increase in discrimination compared with the stage, size, grade and necrosis (SSIGN) score alone was 5.8 % for the GPS, 1.1-1.4 % for the NLR, 2.9-3.4 % for the MLR, 2.0-3.3 % for the PLR and 1.4-3.0 % for the PNI. On the simultaneous multivariable analysis of all candidate measures, the final multivariable model contained the SSIGN score (HR 1.40, P < 0.001), the GPS (HR 2.32, P < 0.001) and the MLR (HR 5.78, P = 0.003) as significant variables. Adding both the GPS and the MLR increased the discrimination of the SSIGN score by 6.2 % and improved the clinical net benefit., Conclusions: In patients with clinically localized CCRCC, the GPS and the MLR appear to be the most relevant prognostic measures of systemic inflammatory response. They may be used as an adjunct for patient counseling, tailoring management and clinical trial design.

Purpose of Review: Herein, we review the various recently published nephrometry scoring systems and the available data on their ability to predict clinical outcomes and their usefulness for new operative techniques., Recent Findings: Several studies showed that the preoperative aspects and dimensions used for anatomical classification score, the RENAL system, and the centrality index are reproducible and able to predict certain clinical intraoperative and postoperative variables in patients undergoing nephron-sparing surgery. Addition of variables, such as the BMI, to the pre-existing scores might improve their predictive abilities., Summary: Nephrometry scoring systems may allow better preoperative planning and counseling of patients. If they gain widespread use in clinical practice, they may also help to give reliable comparisons of morbidity rates among different partial nephrectomy techniques, individual surgeons, and institutions.

Objectives: To evaluate the prognostic value of the Bajorin criteria in a multi-institutional cohort of patients with disease recurrence after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). To investigate whether clinical, pathological and/or biological factors at time of disease recurrence are also associated with cancer-specific outcomes in these patients., Patients and Methods: We identified 242 patients with disease recurrence after RNU for UTUC from 11 centres. With regard to the Bajorin criteria, patients were categorized into three groups based on two risk factors: Karnofsky performance status <80% and the presence of visceral metastasis. Assessed variables included pathological characteristics, time to disease recurrence, age-adjusted Charlson comorbidity index (ACCI), American Society of Anesthesiologists (ASA) score, and laboratory tests at time of disease recurrence., Results: Overall, 185 patients died from their disease; the median survival was 9 months. The survival rates at 1 year were 53, 33, and 39% for patients with no (n = 18), one (n = 109) and two (n = 115) risk factors, respectively, with no significant difference between the groups. In univariable analyses, higher pT-stage, tumour necrosis, non-administered salvage chemotherapy, higher ACCI score, higher ASA score, lower albumin level and higher white blood cell count were significantly associated with a shorter time to cancer-specific mortality., Conclusions: We confirmed the poor yet variable outcomes of patients with disease recurrence after RNU. While the Bajorin criteria seem to have limited prognostic value in this specific cohort, we found several other clinical variables to be associated with worse cancer-specific mortality. If validated, these factors should be taken into consideration for clinical trial design., (© 2013 The Authors. BJU International © 2013 BJU International.)

Purpose: In the present study, we aimed to determine whether the use of self-retaining barbed sutures (SRBS) instead of conventional sutures during open partial nephrectomy leads to improved surgical outcomes., Patients, Materials and Methods: A retrospective analysis of 50 consecutive patients who underwent open partial nephrectomy for a unicentric renal tumor was performed. In 15 patients, SRBS were used for parenchymal repair during open partial nephrectomy, and in 35 patients, conventional sutures were used. The parameters related to surgical outcomes were recorded and analysis of the total patient population and subgroup analysis according to the preoperative aspects and dimensions used for an anatomical (PADUA) score classification was performed., Results: The preoperative baseline values did not statistically differ between the groups. Analysis of the total patient population showed a significant difference regarding ischemia time (mean  ±  standard deviation) between the SRBS group (15.2 ± 6.9 min), and the conventional suture group (25.7 ± 11.8 min). There was no significant difference between the barbed and conventional sutures with regard to postoperative hemoglobin levels, decline in hemoglobin percentage, or renal function parameters. In subgroup-analysis, a significant difference in ischemia time was only found for PADUA scores 6 and 7, without any effect on the outcome parameters., Conclusions: The use of SRBS in parenchymal repair during open partial nephrectomy appears to be a safe and feasible option with decreased cold ischemia time when compared with conventional sutures. In PADUA subgroup-analysis this difference was only observed for PADUA scores 6 and 7.

Purpose: For the minimally invasive treatment of small renal tumors, laparoscopic cryoablation has emerged as an alternative procedure to minimally invasive partial nephrectomy (laparoscopic, robot-assisted laparoscopic) for selected patients, but there are still limited data regarding its safety and oncologic efficacy. We compare perioperative and oncologic outcomes of laparoscopic cryoablation and laparoscopic partial nephrectomy/robot-assisted laparoscopic partial nephrectomy., Materials and Methods: We searched the literature published until September 2013 from MEDLINE®, Web of Science® and major conference proceedings. We included studies comparing laparoscopic cryoablation and laparoscopic partial nephrectomy/robot-assisted laparoscopic partial nephrectomy if they reported oncologic or perioperative outcomes., Results: Overall 13 retrospective, nonrandomized, observational studies met our inclusion criteria. According to the modified NOS (Newcastle-Ottawa Scale) 7 studies (53%) were considered to be of higher quality. Compared with laparoscopic partial nephrectomy/robot-assisted laparoscopic partial nephrectomy, laparoscopic cryoablation was associated with significantly shorter operative times (weighted mean difference [WMD] 35.45 minutes), lower estimated blood loss (WMD 130.11 ml), shorter length of stay (WMD 1.22 days), and a lower risk of total (RR 1.82), urological (RR 1.99) and nonurological complications (RR 2.33). Patients undergoing laparoscopic cryoablation had a significantly increased risk of local (RR 9.39) and metastatic tumor progression (RR 4.68)., Conclusions: This analysis provides fair evidence that oncologic outcomes are substantially worse for laparoscopic cryoablation than for laparoscopic partial nephrectomy/robot-assisted laparoscopic partial nephrectomy, but laparoscopic cryoablation may be associated with improved perioperative outcomes. Therefore, surgical resection may be encouraged in the majority of cases. Balancing cancer control with the risk of perioperative complications is crucial for patient counseling and selection of the appropriate procedure. Prospective, randomized controlled studies with long-term followup are needed to confirm our findings., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Context: For small renal masses (SRMs), partial nephrectomy (PN) represents the therapeutic standard of care. Laparoscopic cryoablation (LCA) could be regarded as an alternative to surgical excision in selected patients, if perioperative complication rates and oncologic results are comparable., Objective: To perform a cumulative analysis of observational studies regarding oncologic outcomes and perioperative complications of both procedures., Evidence Acquisition: Medline, Embase, and Web of Science searches were performed for clinically localized sporadic SRMs that were treated with PN or LCA. A total of 6785 lesions were analyzed for local and metastatic tumor progression and 10 906 procedures for perioperative complications., Evidence Synthesis: Patients undergoing LCA were significantly older, mean tumor sizes were lower, and mean follow-up duration was shorter (each p<0.001). Following LCA and PN, 8.5% and 1.9% developed local tumor progression, respectively (p<0.001). In multivariable analysis, the relative risk for local tumor progression of LCA versus PN was 5.24-fold increased (p<0.001); the risk of metastatic progression was similar. The overall complication rate was higher following PN (23.5% vs 17.0%; p<0.001), especially the rate of major complications (19.2% vs 10.2%; p<0.001). In multivariable analysis, the total risk for complications and major complications for PN versus LCA was 4.6-fold (p=0.004) and 9.71-fold (p<0.001) increased, respectively. Limitations of this analysis include follow-up and selection bias, and lack of standardization reporting complications and outcomes., Conclusions: Both PN and LCA are viable options for the management of SRMs. Compared with PN, LCA results in a higher risk of local tumor progression. The risk of perioperative complications appears to be lower following LCA; however, this difference is strongly influenced by selection bias, and thus limited conclusions can be made regarding true differences in complications. Therefore, PN is the gold standard for SRMs, but LCA may be indicated in selected patients with significant comorbidity., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: To directly compare perioperative, oncologic, and functional outcomes of laparoscopic renal cryoablation and open partial nephrectomy using a matched pair analysis., Patients and Methods: A total of 41 patients who underwent laparoscopic cryoablation for an incidental, solid clinical T(1a)N(0)M(0) renal tumor were matched with 82 patients who received partial nephrectomy in cold ischemia, using optimal matching based on propensity scores, which were created on the basis of preoperative aspects and dimensions used for an anatomic classification of renal tumors (PADUA) score, preoperative glomerular filtration rate, age-adjusted Charlson comorbidity index, and sex. Median follow-up was 33.6 months., Results: No differences in the overall incidence of complications (cryoablation, 20%; partial nephrectomy, 17%; P=0.739) and grade of complications (P=0.424) were observed. After cryoablation, local recurrence developed in four patients with renal-cell carcinoma (n=35) after a median duration of 14 months (range 6-18  mos), but none after partial nephrectomy. The 3-year recurrence-free survival probabilities after laparoscopic renal cryoablation vs open partial nephrectomy were 83% vs 100%, respectively (P=0.015). The average decrease of estimated glomerular filtration rate during follow-up was 7.8±3.1  mL/min/1.73  m(2) after laparoscopic cryoablation and 9.8±2.3  mL/min/1.73  m(2) after open partial nephrectomy, which was not statistically significant (P=0.602)., Conclusions: Perioperative complications and renal functional outcomes of laparoscopic cryoablation and open partial nephrectomy are similar; however, laparoscopic cryoablation confers a substantially higher local recurrence risk of about 17% after 3 years. Therefore, laparoscopic renal cryoablation should be reserved for high-risk patients with decreased life expectancy. Careful patient counseling is advocated. Study limitations include the small sample size, the lack of randomization, and the short follow-up.

Objectives: To define the preoperative independent predictors indicating that renal mass has benign histologic features., Methods: A total of 1664 patients with Stage T1-T2N0M0 with a unilateral renal mass underwent nephrectomy. The endpoint at multivariate analysis was benign versus malignant histologic features., Results: The surgical approach (odds ratio [OR] 2.9, P = .0001), sex (OR 1.97, P = .0001), and age (OR 1.01, P = .007) were independent predictors for the malignant-benign distinction. Malignant tumors were more likely to occur in men (878 of 1009, 87%) versus women (515 of 651, 79%; P <.001). A weak relationship was found between an increasing tumor size and malignancy risk in men only. High-grade renal cell carcinoma was more prevalent in men (31% versus 21%, P = .001). The histologic tumor types were distributed differently between the 2 sexes: 8% papillary renal cell carcinoma in women versus 16% in men, 86% and 78% clear cell renal cell carcinoma, 33% and 57% oncocytoma, and 40% versus 12% angiomyolipoma, respectively. The physician's preoperative judgment regarding tumor amenability for nephron-sparing surgery resulted in patient selection: 10% benign tumors for radical nephrectomy versus 25% for partial nephrectomy (P = .001) and 31% versus 20% high-grade tumors, respectively (P = .0001)., Conclusions: Renal tumors were consistently benign in 20% of women, regardless of size. In contrast, in men, the malignancy risk increased slightly with tumor size. The surgeons' preoperative decision regarding nephron-sparing surgery caused a selection bias in favor of benign lesions, regardless of sex. Our findings support the possibility of basing treatment decisions on the preoperative biopsy findings. Such changes could alter current practice and limit treatment of histologically proven benign lesions to surveillance or ablation only., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Purpose: We developed and externally validated a prognostic nomogram specifically for papillary renal cell carcinoma., Materials and Methods: We retrospectively studied 435 patients who underwent radical or partial nephrectomy for papillary renal cell carcinoma at 3 institutions. Slides were reviewed by 1 uropathologist per institution. We constructed a nomogram predicting 5-year disease specific survival as a graphic representation of significant variables on multivariate Cox proportional hazards regression analysis using data on 258 patients from 2 of the 3 institutions. Nomogram discrimination and calibration were assessed by bootstrapping to obtain relatively unbiased estimates. External validation was done in 177 patients from a third institution., Results: At a median 50.8-month followup 77 papillary renal cell carcinoma related deaths had occurred. In the multivariate Cox proportional hazards model incidental detection, T classification, M classification, vascular invasion and tumor necrosis extent were retained as independent prognostic factors of disease specific survival and formed the basis of the nomogram. The nomogram predicted well with a 93.6% bootstrapped corrected concordance index and showed good calibration. External independent validation revealed 94.2% predictive accuracy., Conclusions: We developed a highly accurate tool specifically for papillary renal cell carcinoma using basic clinical and pathological information to predict disease specific survival. This tool should be helpful to identify papillary renal cell carcinoma with aggressive clinical behavior and may contribute to the ability to individualize postoperative surveillance and therapy., (Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Cytoreductive nephrectomy has a survival advantage in select patients. Patients with sarcomatoid features are known to have poor outcomes. We reviewed the role of surgery in this population to see if these patients could be identified preoperatively., Materials and Methods: Cytoreductive nephrectomy cases identified as having sarcomatoid features or spindle cells were reviewed. The histology, grade, and the presence and percentage of sarcomatoid elements were recorded. Clinicopathological characteristics, survival and systemic therapy were compared to cases without sarcomatoid histology., Results: A total of 62 tumors with sarcomatoid histology were identified, accounting for 14.9% of the 417 patients undergoing cytoreductive nephrectomy. The percentage of sarcomatoid transformation widely varied with a range of 2% to 100% and a mean/median of 49.8%/50%. An increased percentage of sarcomatoid features is associated with a worse prognosis. Patients with and those without sarcomatoid features had similar clinical characteristics. In the sarcomatoid group a higher T stage (p <0.001) and increased incidence of nonclear cell histology (p <0.001) were noted. Median survival of patients with sarcomatoid features was 4.9 vs 17.7 months for nonsarcomatoid histology (p <0.001). Use of postoperative therapy was significantly worse for patients with sarcomatoid histology., Conclusions: Patients with sarcomatoid histology undergoing cytoreductive nephrectomy have a dire prognosis despite aggressive surgery and postoperative therapy. The variability in the sarcomatoid component and the lack of specific clinical features make preoperative identification challenging. Research should focus on identifying biomarkers for this subset of tumors that may allow up-front systemic therapy with surgery reserved for responding patients.

Background: An Eastern Cooperative Oncology Group performance status (ECOG PS) of 2/3 can quantify cancer patients' well being and may be used to select patients for treatment. The objective of the current study was to investigate the outcomes of cytoreductive nephrectomy (CN) for patients who have an impaired performance status (ECOG PS 2/3)., Methods: Patients who underwent CN for renal cell carcinoma (RCC) between 1989 and 2006 were identified. Patient records were reviewed for age, symptoms, ECOG PS, tumor size, stage, grade, histology, sarcomatoid features, lymph node metastasis, site of metastasis, and the presence of bone metastases (BM) in weight-bearing structures. The relation of ECOG PS to outcome variables was evaluated., Results: Four hundred eighteen patients underwent CN, including 117 patients who had an ECOG PS of 0, 274 patients who had an ECOG PS of 1, and 27 patients who had an ECOG PS of 2/3. Patients who had a worse ECOG PS were younger, had higher tumor classification and grade, and more frequently demonstrated anemia and BM. Only 37.5% of patients who had an ECOG PS of 2/3 experienced an improvement in performance in the postoperative period, and only 57.5% went on to receive systemic therapy, of whom none attained an objective responses. The median disease-specific survival for patients who had an ECOG PS of 0, 1, and 2/3 was 27 months, 13.8 months, and 6.6 months, respectively (P<.001). Patients who had an ECOG PS of 2/3 could be stratified further by the presence or absence of BM into 2 groups (median disease-specific survival: 17.7 months and 2.1 months, respectively; P = .006)., Conclusions: Surgery in patients who have a poor performance may serve a palliative function but should be performed with caution because of the poor outcome of such patients. ECOG PS is influenced strongly by BM. A subset of patients with an ECOG PS of 2/3 that are symptomatic specifically from BM may derive greater benefit from CN than patients who hare symptomatic because of visceral metastases., ((c) 2008 American Cancer Society.)

Purpose: Through its binding with interferon inducible angiostatic chemokines the chemokine receptor CXCR3 has an important role in regulating tumor mediating immunity, angiogenesis and metastatic spread. To evaluate its role in the biology of clear cell renal cell carcinoma we performed a tissue microarray based study., Materials and Methods: The tissue microarray comprised 154 patients who underwent nephrectomy for localized (N0M0) clear cell renal cell carcinoma at UCLA from 1989 to 2000. Immunohistochemical staining was evaluated by 2 anatomical pathologists who were blinded to outcome. The end point of this study was disease-free survival. Median followup was 5.9 years., Results: A total of 96% of the tumor specimens stained positive for CXCR3. The mean percent of cells staining positive was 68% (range 0 to 100%). CXCR3 expression was not associated with other common clinicopathological features, such as Eastern Cooperative Oncology Group performance status, T stage, Fuhrman grade, vascular invasion or sarcomatoid features. Patients with low CXCR3 expression (less than 30%) had a significantly worse prognosis than patients with high CXCR3 expression with a 5-year disease-free survival rate of 57% vs 82% (p = 0.009). Multivariate Cox regression analysis retained T stage, Eastern Cooperative Oncology Group performance status, sarcomatoid features and CXCR3 as independent prognostic factors., Conclusions: CXCR3 is a novel molecular marker in patients with clear cell renal cell carcinoma. Its higher expression is an independent predictor of improved disease-free survival following nephrectomy for localized disease. Since CXCR3 is not associated with other clinicopathological prognostic factors, it may represent an ideal complementary molecular marker for identifying patients who are at higher risk for recurrence after nephrectomy.

The treatment of renal tumors with the technique of partial nephrectomy continues to evolve. The relevant literature reviewed confirmed the excellent oncological outcomes associated with partial nephrectomy in properly selected patients. In addition, much data is being accumulated regarding the safety and efficacy of this technique via a laparoscopic approach. With either approach, the chance for renal preservation would appear to be a major benefit while "non-hilar" clamping techniques during the open approach may maximize the likelihood for maintenance of long-term renal function.

Objectives: To compare cancer-specific mortality in patients with unclassified renal cell carcinoma (URCC) vs clear cell RCC (CRCC) after nephrectomy, as URCC is a rare but very aggressive histological subtype., Patients and Methods: Eighty-five patients with URCC and 4322 with CRCC were identified within 6530 patients treated with either radical or partial nephrectomy at 18 institutions. Of 85 patients with URCC, 55 were matched with 166 of 4322 for grade, tumour size, and Tumour, Node and Metastasis stages. Kaplan-Meier and life-table analyses were used to address RCC-specific survival. Subsequently, multivariate Cox regression analyses were used to test for differences in RCC-specific survival in unmatched samples., Results: Of patients with URCC, 80% had Fuhrman grades III or IV, vs 37.8% for CRCC. Moreover, 36.5% of patients with URCC had pathologically confirmed nodal metastases, vs 8.6% with CRCC. Finally, 54.1% of patients with URCC had distant metastases at the time of nephrectomy, vs 16.8% with CRCC. Despite these differences in the overall analyses, after matching for tumour characteristics, the URCC-specific mortality rate was 1.6 times higher (P = 0.04) in matched analyses and 1.7 times higher (P = 0.001) in multivariate analyses., Conclusions: These findings indicate that URCC presents with a higher stage and grade, and even after controlling for the stage and grade differences, predisposes patients to 1.6-1.7 times the mortality of CRCC.

Objective: To define the prognostic relevance of capsular involvement (invasion with no penetration) and collecting-system invasion in patients with stage I (pT1N0M0) and stage II (pT2N0M0) renal cell carcinoma (RCC), by evaluating the outcome of patients treated with nephrectomy., Patients and Methods: In all, 519 patients from a kidney cancer database treated with nephrectomy for stage I and II RCC between 1985 and 2005 were assessed retrospectively. The primary endpoint was recurrence-free survival time. The prognostic relevance of capsular involvement and collecting-system invasion were examined using univariate and multivariate survival analysis., Results: Capsular involvement and collecting-system invasion were evident in 112 (21.6%) and 39 (7.5%) patients, respectively. Capsular involvement was associated with higher Fuhrman grades and larger tumours. The incidence of collecting-system invasion was higher in patients with microvascular invasion. The median follow-up was 49 months. In univariate analysis, patients with capsular involvement and collecting-system invasion had a worse prognosis than patients without (P = 0.007 and <0.001, respectively). In multivariate analysis, capsular involvement (hazard ratio 1.84, P = 0.036) and collecting-system invasion (3.78, P < 0.001) were independent prognostic factors of recurrence-free survival. Interestingly, there was no survival difference between patients with capsular involvement in stage I/II and patients with invasion of perinephric tissue (pT3aN0M0)., Conclusions: These findings suggest that capsular involvement and collecting-system invasion are poor prognostic findings in stage I and II RCC. They should both be considered when planning the follow-up. A revised pT3a stage including patients with capsular involvement could improve its prognostic validity.

Background: To explore predictors of positive surgical margins (PSM) after robotic partial nephrectomy (PN) in a large multicenter international observational project, harnessing the Surface-Intermediate-Base (SIB) margin score to report the resection technique after PN in a standardized way. Methods: Data from consecutive patients with cT1-2N0M0 renal masses treated with PN from September 2014 to March 2015 at 16 tertiary referral centers and included in the SIB margin score International Consortium were prospectively collected. For the present study, only patients treated with robotic PN were included. Uni- and multivariable analysis were fitted to explore clinical and surgical predictors of PSMs after PN. Results: Overall, 289 patients were enrolled. Median (IQR) preoperative tumor size was 3.0 (2.3–4.2) cm and median (IQR) PADUA score was 8 (7–9). SIB scores of 0–2 (enucleation), 3–4 (enucleoresection) and 5 (resection) were reported in 53.3%, 27.3% and 19.4% of cases, respectively. A PSM was recorded in 18 (6.2%) patients. PSM rate was 4.5%, 11.4% and 3.6% in case of enucleation, enucleoresection and resection, respectively. Patients with PSMs had tumors with a higher rate of contact with the urinary collecting system (55.6% vs. 27.3%; p < 0.001) and a longer median warm ischemia time (22 vs. 16 min; p = 0.02) compared with patients with negative surgical margins, while no differences emerged between the two groups in terms of other tumor features (i.e., pathological diameter, PADUA score). In multivariable analysis, only enucleoresection (SIB score 3–4) versus enucleation (SIB score 0–2) was found to be an independent predictor of PSM at final pathology (HR: 2.68; 95% CI: 1.25–7.63; p = 0.04), while resection (SIB score 5) was not. Conclusions: In our experience, enucleoresection led to a higher risk of PSMs as compared to enucleation. Further studies are needed to assess the differential impacts of resection technique and surgeon's experience on margin status after robotic PN. [ABSTRACT FROM AUTHOR]

We aimed to compare the outcomes of open vs robotic partial nephrectomy (PN), focusing on predictors of Trifecta failure in patients with highly complex renal masses. We queried the prospectively collected database from the SIB International Consortium, including 507 consecutive patients with cT1-2N0M0 renal masses treated at 16 high-volume referral centres, to select those with highly complex (PADUA score ≥10) tumors undergoing PN. RT was classified as enucleation, enucleoresection or resection according to the SIB score. Trifecta was defined as achievement of negative surgical margins, no acute kidney injury and no Clavien-Dindo grade ≥2 postoperative surgical complications. Multivariable logistic regression analysis was used to assess independent predictors of Trifecta failure. 113 patients were included. Patients undergoing open PN (n = 47, 41.6%) and robotic PN (n = 66, 58.4%) were comparable in baseline characteristics. RT was classified as enucleation, enucleoresection and resection in 46.9%, 34.0% and 19.1% of open PN, and in 50.0%, 40.9% and 9.1% of robotic PN (p = 0.28). Trifecta was achieved in significantly more patients after robotic PN (69.7% vs. 42.6%, p = 0.004). On multivariable analysis, surgical approach (open vs robotic, OR: 2.62; 95%CI: 1.11–6.15, p = 0.027) and tumor complexity (OR for each additional unit of the PADUA score: 2.27; 95%CI: 1.27–4.06, p = 0.006) were significant predictors of Trifecta failure, while RT was not. The study is limited by lack of randomization; as such, selection bias and confounding cannot be entirely ruled out. Tumor complexity and surgical approach were independent predictors of Trifecta failure after PN for highly complex renal masses. [ABSTRACT FROM AUTHOR]

Purpose: Currently there are no specific guidelines for the post-operative follow-up of chromophobe renal cell carcinoma (chRCC). We aimed to evaluate the pattern, location and timing of recurrence after surgery for non-metastatic chRCC and establish predictors of recurrence and cancer-specific death. Methods: Retrospective analysis of consecutive surgically treated non-metastatic chRCC cases from the Royal Free London NHS Foundation Trust (UK, 2015–2019) and the international collaborative database RECUR (15 institutes, 2006–2011). Kaplan–Meier curves were plotted. The association between variables of interest and outcomes were analysed using univariate and multivariate Cox proportional hazards regression models with shared frailty for data source. Results: 295 patients were identified. Median follow-up was 58 months. The five and ten-year recurrence-free survival rates were 94.3% and 89.2%. Seventeen patients (5.7%) developed recurrent disease, 13 (76.5%) with distant metastases. 54% of metastatic disease diagnoses involved a single organ, most commonly the bone. Early recurrence (< 24 months) was observed in 8 cases, all staged ≥ pT2b. 30 deaths occurred, of which 11 were attributed to chRCC. Sarcomatoid differentiation was rare (n = 4) but associated with recurrence and cancer-specific death on univariate analysis. On multivariate analysis, UICC/AJCC T-stage ≥ pT2b, presence of coagulative necrosis, and positive surgical margins were predictors of recurrence and cancer-specific death. Conclusion: Recurrence and death after surgically resected chRCC are rare. For completely excised lesions ≤ pT2a without coagulative necrosis or sarcomatoid features, prognosis is excellent. These patients should be reassured and follow-up intensity curtailed. [ABSTRACT FROM AUTHOR]

Using a European database of contemporary patients with renal cell carcinoma (RCC), we provided estimated survival time benchmarks for placebo arms of studies using immunotherapy after nephrectomy for patients with high-risk RCC. This data can be directly used to better select patients for RCC-adjuvant studies and optimize the design of future trials. Introduction: Designing adjuvant trials is challenging because of uncertainties of prevalence and outcome of high-risk renal cell cancer (RCC) despite use of validated risk scores. Our objective is to investigate how differences in eligibility criteria may impact on potential study results in RCC adjuvant trials. Patients and Methods: RECUR is a multicenter European database capturing patient and tumor characteristics, recurrence patterns, and survival of those curatively treated for non-metastatic RCC from 2006 to 2011 without any adjuvant therapy. We used RECUR to evaluate prevalence, disease-free survival (DFS), and overall survival (OS) according to eligibility criteria of immunotherapybased adjuvant trials IMMotion 010 (NCT03024996), Checkmate 914 (NCT03138512), Keynote-564 (NCT03142334), RAMPART (NCT03288532), and PROSPER (NCT03055013). Results: Of 3024 relevant patients in RECUR, 408 (13.5%), 725 (24%), 609 (20.1%), 1363 (45.1%), and 1071 (35.4%) met eligibility criteria for IMMotion-010, CheckMate-914, Keynote-564, RAMPART, and PROSPER, respectively. The median and 5-year DFS Kaplan-Meier estimates in RECUR corresponding to each trial eligibility criteria were: not reached and 69.6% for RAMPART; not reached and 64.5% for PROSPER; 109.3 months (95% confidence interval [CI], 83.9-134.6 months) and 57% for CheckMate-914; 75.8 months (95% CI, 52.7-98.8 months) and 54.3% for Keynote-564; and 43.6 months (95% CI, 30.8-56.4 months) and 45% for IMMotion-010. Our analysis may be limited by the retrospective design. Conclusions: RECUR provides estimated DFS and OS benchmarks for placebo arms of adjuvant checkpoint inhibitor studies and hence likely time to trial reporting. Well-documented contemporary registries rather than past risk models should be used to design future adjuvant trials. [ABSTRACT FROM AUTHOR]

Context A detailed understanding of renal surgical anatomy is necessary to optimize preoperative planning and operative technique and provide a basis for improved outcomes. Objective To evaluate the literature regarding pertinent surgical anatomy of the kidney and related structures, nephrometry scoring systems, and current surgical strategies for partial nephrectomy (PN). Evidence acquisition A literature review was conducted. Evidence synthesis Surgical renal anatomy fundamentally impacts PN surgery. The renal artery divides into anterior and posterior divisions, from which approximately five segmental terminal arteries originate. The renal veins are not terminal. Variations in the vascular and lymphatic channels are common; thus, concurrent lymphadenectomy is not routinely indicated during PN for cT1 renal masses in the setting of clinically negative lymph nodes. Renal-protocol contrast-enhanced computed tomography or magnetic resonance imaging is used for standard imaging. Anatomy-based nephrometry scoring systems allow standardized academic reporting of tumor characteristics and predict PN outcomes (complications, remnant function, possibly histology). Anatomy-based novel surgical approaches may reduce ischemic time during PN; these include early unclamping, segmental clamping, tumor-specific clamping (zero ischemia), and unclamped PN. Cancer cure after PN relies on complete resection, which can be achieved by thin margins. Post-PN renal function is impacted by kidney quality, remnant quantity, and ischemia type and duration. Conclusions Surgical renal anatomy underpins imaging, nephrometry scoring systems, and vascular control techniques that reduce global renal ischemia and may impact post-PN function. A contemporary ideal PN excises the tumor with a thin negative margin, delicately secures the tumor bed to maximize vascularized remnant parenchyma, and minimizes global ischemia to the renal remnant with minimal complications. Patient summary In this report we review renal surgical anatomy. Renal mass imaging allows detailed delineation of the anatomy and vasculature and permits nephrometry scoring, and thus precise, patient-specific surgical planning. Novel off-clamp techniques have been developed that may lead to improved outcomes. [ABSTRACT FROM AUTHOR]

Objective To validate high-sensitivity C-reactive protein (hs- CRP) serum levels as an independent marker for disease-free survival ( DFS) in clinically localised clear cell renal cell carcinoma ( ccRCC)., Patients and Methods In all, 403 consecutive patients with clinically localised ( T1-3N0M0) ccRCC treated by radical or partial nephrectomy were enrolled., Preoperative serum levels of hs- CRP were evaluated as both a continuous and categorical variables., Associations with clinical (age, gender) and pathological variables ( T classification, grade, tumour necrosis) were assessed with the chi-square and Kruskal- Wallis tests., Univariable and multivariable Cox proportional hazards models were fitted. The prognostic accuracy ( PA) was assessed with Harrell's C-index., Results The mean hs- CRP level was 1.32 mg/dL. The hs- CRP levels were associated with T classification ( P = 0.05), high-grade disease (P < 0.001) and tumour necrosis ( P = 0.003)., After a median follow-up of 43 months, 41 patients (10.1%) had developed disease recurrence. With each unit increase in hs- CRP levels, the risk of recurrence increased by 10% (hazard ratio 1.10, P = 0.015)., The thresholds of 0.5 and 0.75 mg/dL showed the best discrimination for stratification of patients according to the probability of recurrence., These categorically coded hs- CRP levels were identified as independent prognostic factors in multivariable analyses ( P < 0.001) and led to a significant increase in the PA of a multivariable base model containing the variables of the 'Stage, Size, Grade and Necrosis' ( SSIGN) score., Conclusions This study validates preoperative serum hs- CRP levels as independent prognostic factor after surgery for localised ccRCC., Hs-CRP may be included in standard prognostic modelling after surgery and may guide surveillance and inclusion in adjuvant clinical trials. [ABSTRACT FROM AUTHOR]