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Background: Careful patient selection is critical when considering cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) but few studies have investigated the prognostic value of radiologic features that measure tumor burden., Objective: To develop a prognostic model to improve CN selection with integration of common radiologic features with known prognostic factors associated with mortality in the first year following surgery., Design, Settings, and Participants: Data were analyzed for consecutive patients with mRCC treated with upfront CN at five institutions from 2006 to 2017. Univariable and multivariable models were used to evaluate radiographic features and known risk factors for associations with overall survival. Relevant factors were used to create the SCREEN model and compared to the International mRCC Database Consortium (IMDC) model for predictive accuracy and clinical usefulness., Results and Limitations: A total of 914 patients with mRCC were treated with upfront CN during the study period. Seven independently predictive variables were used in the SCREEN score: three or more metastatic sites, total metastatic tumor burden ≥5 cm, bone metastasis, systemic symptoms, low serum hemoglobin, low serum albumin, and neutrophil/lymphocyte ratio ≥4. Predictive accuracy measured as the area under the receiver operating characteristic curves was 0.76 for the SCREEN score and 0.55 for the IMDC model. Decision curve analysis showed that the SCREEN model was useful beyond the IMDC classifier for threshold first-year mortality probabilities between 15% and 70%., Conclusions: The SCREEN score had higher predictive accuracy for first-year mortality compared to the IMDC scheme in a multi-institutional cohort and may be used to improve CN selection., Patient Summary: This study provides a model to improve selection of patients with metastatic kidney cancer who may benefit from surgical removal of the primary kidney tumor. We found that radiographic measurements of the tumor burden predicted the risk of death in the first year after surgery. The model can be used to improve decision-making by these patients and their physicians., (Copyright © 2023. Published by Elsevier B.V.)

Objective: UGN-101 has been approved for the chemoablation of low-grade upper tract urothelial cancer (UTUC) involving the renal pelvis and calyces. Herein is the first reported cohort of patients with ureteral tumors treated with UGN-101., Patients and Methods: We performed a retrospective review of patients treated with UGN-101 for UTUC at 15 high-volume academic and community centers focusing on outcomes of patients treated for ureteral disease. Patients received UGN-101 with either adjuvant or chemo-ablative intent. Response rates are reported for patients receiving chemo-ablative intent. Adverse outcomes were characterized with a focus on the rate of ureteral stenosis., Results: In a cohort of 132 patients and 136 renal units, 47 cases had tumor involvement of the ureter, with 12 cases of ureteral tumor only (8.8%) and 35 cases of ureteral plus renal pelvic tumors (25.7%). Of the 23 patients with ureteral involvement who received UGN-101 induction with chemo-ablative intent, the complete response was 47.8%, which did not differ significantly from outcomes in patients without ureteral involvement. Fourteen patients (37.8%) with ureteral tumors had significant ureteral stenosis at first post-treatment evaluation, however, when excluding those with pre-existing hydronephrosis or ureteral stenosis, only 5.4% of patients developed new clinically significant stenosis., Conclusions: UGN-101 appears to be safe and may have similar efficacy in treating low-grade urothelial carcinoma of the ureter as compared to renal pelvic tumors., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Solomon Woldu receives honoraria for consulting for UroGen Pharma Ltd. Yair Lotan is involved in research with Pacific Edge Inc., Cepheid Inc., MDx Health and received honoraria for consulting for Nanorobotics, C2I genomics, Photocure, Astra-Zeneca, Merck, Fergene, Abbvie, Nucleix, Ambu, Seattle Genetics, Hitachi, Ferring Research, Verity Pharmaceutics, Virtuoso Surgical, Stimit, Urogen Pharma Ltd, Vessi medical, CAPs medical, Xcures, BMS, Nonagen, Aura Biosciences, Inc., Convergent Genomics, Pacific Edge, Pfizer, Phinomics Inc, CG oncology, Uroviu, On target lab., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To evaluate factors associated with perioperative outcomes in a multi-institutional cohort of patients treated with cytoreductive nephrectomy (CN)., Methods: Data were analyzed for metastatic renal cell carcinoma patients treated with CN at 6 tertiary academic centers from 2005 to 2019. Outcomes included: Clavien-Dindo complications, mortality, length of hospitalization, 30-day readmission rate, and time to systemic therapy. Univariate and multivariable models evaluated associations between outcomes and prognostic variables including the year of surgery., Results: A total of 1272 consecutive patients were treated with CN. Patients treated in 2015-2019 vs 2005-2009 had better performance status (P<.001), higher pathologic N stage (P = .04), more frequent lymph node dissections (P<.001), and less frequent presurgical therapy (P = .02). Patients treated in 2015-2019 vs 2005-2009 had lower overall and major complications from surgery, 22% vs 39%, P<.001% and 10% vs 16%, P = .03. Mortality at 90days was higher for patients treated 2005-2009 vs 2015-2019; 10% vs 5%, P = .02. After multivariable analysis, surgical time period was an independent predictor of major complications and 90-day mortality following cytoreductive surgery., Conclusion: Postoperative major complications and mortality rates following CN are significantly lower in patients treated within the most recent time period., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2023. Published by Elsevier Inc.)

Background: Intracavitary UGN-101 is approved for the treatment of low-grade noninvasive upper tract urothelial carcinoma (UTUC). Post-commercialization studies underscore the benefit of UGN-101 administration for patients with imperative indications for whom radical nephroureterectomy (RNU) is not a viable option., Objective: To describe the use, efficacy, and safety of UGN-101 in patients with UTUC with imperative indications for renal preservation, including high-grade disease., Design, Setting, and Participants: Patients receiving UGN-101 with imperative indications were retrospectively analyzed using a multicenter centralized registry from 15 high-volume academic and community centers., Outcome Measurements and Statistical Analysis: We defined imperative indications as patients with a solitary kidney, the presence of chronic kidney disease (CKD) with a glomerular filtration rate <30 ml/min, bilateral UTUC, and patients unfit for or unwilling to undergo surgical extirpation. Tumor characteristics, disease progression/recurrence, and adverse events were recorded on a per-renal-unit basis., Results and Limitations: UGN-101 was instilled into 52 renal units (38%) in 48 patients for imperative indications, including 29 patients (56%) with a solitary kidney, 11 kidneys (21%) in the setting of bilateral UTUC, six patients (12%) with CKD, and six patients (12%) who were unfit for or unwilling to undergo RNU. Twelve renal units had biopsy-proven high-grade papillary disease. Tumors were completely ablated before induction therapy in 34% of cases, while 66% had tumor present. Following induction therapy, 17 patients (40%) had no evidence of disease (NED) on ureteroscopy, 88% of whom maintained this status at median follow-up of 10.8 mo. In the cohort with high-grade disease, five patients (45%) had NED at initial post-induction primary disease evaluation. Adverse events included pyelonephritis (8%), ureteral stenosis (8%), anemia (6%), and acute renal failure (4%). Limitations include the retrospective study design, the lack of long-term follow up, and patient selection bias., Conclusions: Intracavitary therapy with UGN-101 in patients with UTUC and imperative indications shows promise as a kidney-sparing treatment modality. While long-term follow-up is needed, this intracavitary treatment may help in prolonging time to RNU and delaying the morbidity of hemodialysis in this comorbid population., Patient Summary: We reviewed results for patients with cancer in the upper urinary tract and an additional condition that would not allow kidney removal who received treatment with a gel called UGN-101. Our results suggest that UGN-101 shows promise as a kidney-sparing treatment. It may delay the time until kidney removal is needed in these patients and avoid the negative effects associated with dialysis., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Importance: Level I evidence has failed to demonstrate an overall survival (OS) advantage for cytoreductive nephrectomy in patients with metastatic clear cell renal cell carcinoma (ccRCC) in the modern era, which is at odds with observational studies reporting a marked OS benefit associated with these operations. These observational studies were not designed to adjust for unmeasured confounding., Objective: To assess whether cytoreductive nephrectomy is associated with improved OS in patients with metastatic ccRCC., Design, Setting, and Participants: This cohort study identified patients with metastatic ccRCC in the National Cancer Database from January 1, 2006, to December 31, 2016, who received systemic targeted therapy. The analysis was finalized on July 23, 2021., Exposures: Receipt of cytoreductive nephrectomy., Main Outcomes and Measures: The primary outcome was OS from the date of diagnosis to death or censoring at last follow-up. Distance from the patients' zip code of residence to the treating facility was identified as a valid instrument and was used in a 2-stage residual inclusion instrumental variable analysis. Conventional adjustments for selection bias, multivariable Cox proportional hazards regression, and propensity score matching were performed for comparison. Measured covariates adjusted for in all analyses included age, sex, race, Charlson-Deyo score, facility type, year of diagnosis, clinical T stage, and clinical N stage., Results: The final study population included 12 766 patients (median age, 63 years; IQR, 56-70 years; 8744 [68%] male; 11 206 [88%] White). Cytoreductive nephrectomy was performed in 5005 patients (39%). Conventional adjustments for selection bias demonstrated a significant OS benefit associated with cytoreductive nephrectomy (multivariable Cox proportional hazards regression: hazard ratio [HR], 0.49; 95% CI, 0.47-0.51; propensity score matching: HR, 0.48; 95% CI, 0.46-0.50). Instrumental variable estimates did not demonstrate an association between cytoreductive nephrectomy and OS (HR, 0.92; 95% CI, 0.78-1.09)., Conclusions and Relevance: Instrumental variable analysis did not demonstrate a survival advantage associated with cytoreductive nephrectomy for patients with metastatic ccRCC. This discrepancy likely reflects the fact that surgical indication for cytoreductive nephrectomy is primarily driven by factors that are not commonly measured or available in observational data sets.

A clearer understanding of the tumor immune microenvironment (TIME) in metastatic clear cell renal cell carcinoma (ccRCC) may help to inform precision treatment strategies. We sought to identify clinically meaningful TIME signatures in ccRCC. We studied tumors from 39 patients with metastatic ccRCC using quantitative multiplexed immunofluorescence and relevant immune marker panels. Cell densities were analyzed in three regions of interest (ROIs): tumor core, tumor-stroma interface and stroma. Patients were stratified into low- and high-marker density groups using median values as thresholds. Log-rank and Cox regression analyses while controlling for clinical variables were used to compare survival outcomes to patterns of immune cell distributions. There were significant associations with increased macrophage (CD68 + CD163 + CD206 + ) density and poor outcomes across multiple ROIs in primary and metastatic tumors. In primary tumors, T-bet + T helper type 1 (Th1) cell density was highest at the tumor-stromal interface (P = 0·0021), and increased co-expression of CD3 and T-bet was associated with improved overall survival (P = 0·015) and survival after immunotherapy (P = 0·014). In metastatic tumor samples, decreased forkhead box protein 3 (FoxP3) + T regulatory cell density correlated with improved survival after immunotherapy (P = 0·016). Increased macrophage markers and decreased Th1 T cell markers within the TIME correlated with poor overall survival and treatment outcomes. Immune markers such as FoxP3 showed consistent levels across the TIME, whereas others, such as T-bet, demonstrated significant variance across the distinct ROIs. These findings suggest that TIME profiling outside the tumor core may identify clinically relevant associations for patients with metastatic ccRCC., (© 2021 British Society for Immunology.)

Approximately 10%-20% of patients with clinically localized clear cell renal cell carcinoma (ccRCC) at time of surgery will subsequently experience metastatic progression. Although considerable progression was seen in the systemic treatment of metastatic ccRCC in last 20 years, once ccRCC spreads beyond the confines of the kidney, 5-year survival is less than 10%. Therefore, significant clinical advances are urgently needed to improve overall survival and patient care to manage the growing number of patients with localized ccRCC. We comprehensively evaluated expression of 388 candidate genes related with survival of ccRCC by using TCGA RNAseq (n = 515), Total Cancer Care (TCC) expression array data (n = 298), and a well characterized Moffitt RCC cohort (n = 248). We initially evaluated all 388 genes for association with overall survival using TCGA and TCC data. Eighty-one genes were selected for further analysis and tested on Moffitt RCC cohort using NanoString expression analysis. Expression of nine genes (AURKA, AURKB, BIRC5, CCNE1, MK167, MMP9, PLOD2, SAA1, and TOP2A) was validated as being associated with poor survival. Survival prognostic models showed that expression of the nine genes and clinical factors predicted the survival in ccRCC patients with AUC value: 0.776, 0.821 and 0.873 for TCGA, TCC and Moffitt data set, respectively. Some of these genes have not been previously implicated in ccRCC survival and thus potentially offer insight into novel therapeutic targets. Future studies are warranted to validate these identified genes, determine their biological mechanisms and evaluate their therapeutic potential in preclinical studies., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: Interteam performance and Clavien-Dindo (C-D) complications in renal cell carcinoma with inferior vena cava thrombectomy (RCC-IVCT) have not been reported. We aimed to describe complications by the degree of complexity and surgical teams in a collaborative effort between a National Cancer Institute-designated Comprehensive Cancer Center and a Quaternary Care Teaching Hospital., Methods: Between January 2011 and May 2019, 73 consecutive RCC-IVCT were included. C-D grades III or higher were captured. Teams involved were urologic-oncology, vascular, hepatobiliary/transplant, and cardiothoracic. The Mayo Clinic tumor thrombus classification was used., Results: Overall complication rate was 42% (n = 31). Nineteen percent had grade III, 18% had grade IV, and 6% had grade V complications. Patients with level IV thrombus had the highest in-hospital mortality rate (75%). Thrombus level did not show a correlation to complication rates (14% level I, 45% level II, 32% level III, 42% level IV). A positive correlation found between the number of teams involved and complication rates (35% with 2-team, 59% with 3-team, P = .059). Thromboembolic events (6% vs 24%, P = .02) and disposition other than home (22% vs 48%, P = .01) were statistically lower for the 2-team groups. Two-team in-hospital mortality was 1/51 (2%) versus 3-team (3/22,14%, ( P = .07). No statistical differences were found in infections, thromboembolic events, and grades of complications between surgical teams., Conclusions: Despite similar interteam performance, the consistency of surgeons in high complexity cases could improve outcomes further. Complexity was higher for hepatobiliary/transplant and cardiothoracic teams. A combination of intraoperative events and patient selection (comorbidities and age) contributed to death. Overall, in-hospital mortality was lower than in most reported series.

Introduction: To describe the incidence, contemporary management, risk factors and outcomes of urinary leak following open and robotic partial nephrectomy at a tertiary care, comprehensive cancer center., Materials and Methods: We reviewed 975 patients who underwent partial nephrectomy at Moffitt Cancer Center from January 2009 to May 2017. Patient demographic, perioperative and follow up data was recorded and compared stratified for postoperative urine leak. Fisher's exact and Wilcoxon sum-rank testing were performed for categorical and continuous variables as indicated., Results: Twenty-three of 975 (2.3%) patients experienced a urine leak after partial nephrectomy. Median nephrometry score for urine leak patients was 8 (SD +/- 1.3). Median postoperative days to detection was 3.5 and most leaks were discovered due to high drain output. Operative factors associated with urinary leak included open surgery, estimated blood loss, and not using a sliding-clip renorrhaphy (p < 0.05). Ten (44%) were managed conservatively, 9 (39%) patients required ureteral stent placement, 3 (13%) needed a percutaneous nephrostomy tube, one patient (4%) required percutaneous drainage for urinoma (4%). One patient ultimately failed conservative management and required nephrectomy 45 days after the original surgery. Mean time to stent and drain removal was 40 +/- 17 and 24 +/- 7 days, respectively. Five patients with symptomatic leaks were readmitted with a mean length of stay of 3.2 +/- 1.8 days., Conclusions: The overall incidence of urinary leak after partial nephrectomy remains low regardless of surgical approach. Perioperative characteristics such as tumor complexity and high blood loss, in addition to open surgery and not using a sliding-clip bolstered renorrhaphy are associated with urine leak.

Background: The neutrophil-lymphocyte ratio (NLR) is an established signature of inflammation used for evaluating renal cell carcinoma (RCC)., Objective: To determine the utility of NLR and its relationship with known risk factors associated with poor survival in patients with metastatic RCC and tumor thrombus undergoing cytoreductive nephrectomy (CN)., Design, Setting, and Participants: Prognostic variables were reviewed for patients undergoing CN with thrombectomy between 2000 and 2014 from six different institutions. Patients were stratified for NLR >4.0 based on cut point analysis., Outcome Measurements and Statistical Analysis: Kaplan-Meier curves compared overall survival of the total cohort and established risk models (Memorial Sloan Kettering Cancer Center [MSKCC], International Metastatic Renal-Cell Carcinoma Database Consortium [IMDC], and M.D. Anderson Cancer Center [MDACC]) stratified by NLR. Multivariable Cox regression determined predictors of overall survival. Receiver operator characteristic curves tested the predictive accuracy of survival ≥12 mo, and area under the curve (AUC) was compared between models., Results and Limitations: In total, 332 patients were identified. Patients with NLR ≤4.0 had longer median survival (24.7 vs 15.2 mo, p=0.004). NLR >4.0 distinguished patients with significantly shorter survival for non-poor-risk groups defined by MSKCC, IMDC, and MDACC criteria. Systemic symptoms, low hemoglobin, elevated lactate dehydrogenase, retroperitoneal adenopathy, level IV thrombus, elevated absolute neutrophil count, and NLR >4 were independent predictors of decreased survival (p<0.05). These factors had higher predictive accuracy for survival at 12 mo (AUC=0.755) than MKSCC, IMDC, and MSKCC models., Conclusions: NLR >4.0 independently predicts poor survival and further distinguishes established risk model survival curves. We identified seven preoperative risk factors related to poor survival for patients with metastatic RCC with tumor thrombus undergoing CN., Patient Summary: The neutrophil-lymphocyte ratio and six additional preoperative variables can be used to better council patients regarding survival after surgery for metastatic renal cell carcinoma with tumor thrombus., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate whether incidental pathologic T3a (pT3a) upstaging after partial nephrectomy (PN) for clinical T1 disease results in inferior oncologic outcomes compared to pT1a-b disease., Materials and Methods: Retrospective chart review was completed at the University of Michigan and Moffitt Cancer Center to identify patients undergoing PN for clinical T1 masses between 1995 and 2015. A total of 1955 patients were identified, of which 95 had pT3a upstaging. Median follow-up was 38.2 months. Patients with pT3a disease were individually matched by clinicopathologic features with patients undergoing PN with pT1a-b disease in a 1:2 ratio. Kaplan-Meier analysis and univariate and multivariable Cox proportional hazards regression analysis were performed. Primary endpoint was recurrence-free survival (RFS). Secondary endpoints were all-cause mortality, cancer-specific survival (CSS), and rates of local and distant recurrence., Results: Recurrence rates were significantly higher in pT3a disease compared to pT1a-b controls (P <.01). In those patients with pT3a upstaging, 3- and 5-year RFS were 81% and 58%, compared to 86% and 75% in pT1a-b controls (P = .01). CSS at 3 and 5 years were 91% and 90% in pT3a disease and 100% and 97% in pT1a-b controls (P <.01). All-cause mortality at 3 and 5 years were 82% and 71% in pT3a disease and 93% and 80% in pT1a-b controls (P = .04). Univariate and multivariable analysis of pT3a disease demonstrated no association between demographic or pathologic characteristics and RCC recurrence., Conclusion: Patients with pT3a upstaging following PN experience a significantly reduced RFS and CSS when compared to pT1 disease., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To determine the therapeutic value of lymph node dissection (LND) during cytoreductive nephrectomy (CN) and assess predictors of cancer-specific survival (CSS) in metastatic renal-cell carcinoma., Patients and Methods: We identified 293 consecutive patients treated with CN at 4 academic institutions from March 2000 to May 2015. LND was performed in 187 patients (63.8%). CSS was estimated by the Kaplan-Meier method for the entire cohort and for a propensity score-matched cohort. Cox proportional hazards regression was used to evaluate CSS in a multivariate model and in an inverse probability weighting-adjusted model for patients who underwent dissection., Results: Median follow-up was 12.6 months (interquartile range, 4.47, 30.3), and median survival was 15.9 months. Of the 293 patients, 187 (63.8%) underwent LND. One hundred six patients had nodal involvement (pN+) with a median CSS of 11.3 months (95% confidence interval [CI], 6.6, 15.9) versus 24.2 months (95% confidence interval, 14.1, 34.3) for pN- patients (log-rank P = .002). The hazard ratio for LND was 1.325 (95% CI, 1.002, 1.75) for the whole cohort and 1.024 (95% CI, 0.682, 1.537) in the propensity score-matched cohort. Multivariate analysis revealed that number of positive lymph nodes (P < .001) was a significant predictor of worse CSS., Conclusion: For patients with metastatic renal-cell carcinoma undergoing CN with lymphadenectomy, the number of nodes positive was predictive of survival at short-term follow-up. However, nonstandardized lymphadenectomy only provided prognostic information without therapeutic benefit. Prospective studies with standardized templates are required to further ascertain the therapeutic value of LND., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: We reviewed the outcomes for an octogenarian population to investigate whether active surveillance (AS) provides comparable survival to partial nephrectomy (PN) or radical nephrectomy (RN)., Patients and Methods: Data were collected from 115 octogenarian patients referred for management of renal masses at Moffitt Cancer Center from 2000 to 2013. Patients were treated with AS, PN, or RN. Univariable and multivariable Cox regression models measured the association between management modality and survival. Kaplan-Meier survival analysis was used to calculate survival, and log-rank tests were used to compare survival curves., Results: The median age was 82 years (interquartile range, 81-85 years). The median follow-up period was 51 months (interquartile range, 23-81 months). Of the 115 patients, 31 (27%) underwent AS, 31 (27%) underwent PN, and 53 (46%) underwent RN. The patients who underwent RN had a larger mean tumor size at 5.5 cm, with 19 patients (36%) having stage ≥ pT3 (P < .001). We found no difference in overall survival or disease-specific survival among the 3 management strategies on univariable analysis (P = .39 and P = .1, respectively). On multivariable analysis for overall survival, only the Charlson comorbidity index was associated with worse survival (hazard ratio, 1.2; 95% confidence interval, 1.1-1.3; P = .002). In a subgroup analysis of cT1a patients, we also found no difference in overall or disease-specific survival among the treatment arms on univariable analysis (P = .74 and P = .9, respectively)., Conclusion: Active treatment with PN and RN might not provide a survival advantage compared with AS in the octogenarian population with a small renal mass. However, larger renal masses should undergo active treatment in appropriately selected patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Careful selection is critical to identify those with metastatic renal cell carcinoma who are most likely to benefit from cytoreductive nephrectomy. Surgery in patients who have metastatic renal cell carcinoma with tumor thrombus is complex and may not benefit some patients with poor overall survival. We evaluated whether preoperative variables or risk stratification systems could predict overall survival following cytoreductive nephrectomy., Materials and Methods: Prognostic factors for overall survival after surgery were evaluated in patients who had metastatic renal cell carcinoma with venous tumor thrombus at 5 institutions from 2000 to 2014. Prognostic variables, including metastatic renal cell carcinoma risk models, were evaluated for associations with overall survival. Multivariable analysis was used to determine independent associations of preoperative variables with overall survival., Results: A total of 427 patients with metastatic renal cell carcinoma were identified with tumor thrombus. Patients with inferior vena cava thrombus above the diaphragm had shorter median overall survival vs those with renal vein only thrombus (9.2 months, IQR 4.2-30.8, vs 21.7, IQR 7.7-42.8, p = 0.0165). Individual risk factors from prognostic models were evaluated among other preoperative characteristics for associations with overall survival in 122 patients (32%) who died within 270 days of surgery. Independent predictors of overall survival included lactate dehydrogenase greater than the upper limit of normal (p = 0.003), systemic symptoms (p = 0.003), inferior vena cava thrombus above the diaphragm (p = 0.02) and sarcomatoid features (p = 0.005)., Conclusions: Poor overall survival following cytoreductive nephrectomy in patients with metastatic renal cell carcinoma with tumor thrombus is associated with inferior vena cava thrombus above the diaphragm, poor risk group, systemic symptoms or sarcomatoid dedifferentiation. Patients with expected poor overall survival should be considered for preoperative systemic therapy clinical trials., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The goal was to assess the natural history and management of patients with pathologically proven bilateral (synchronous) RO after undergoing initial partial nephrectomy (PN)., Methods: All patients underwent either robotic/laparoscopic or open PN by two experienced genitourinary oncologists from 2005-2013. Final pathology was determined by surgical excision, CT-guided percutaneous core biopsy (CT-biopsy) or fine needle aspiration (FNA). Patient demographics, tumor characteristics (pathologic data, location, size) type of surgery, pre/post estimated glomerular filtration rate (eGFR) and surgical complications were recorded., Results: Twelve patients were identified with bilateral RO. Median age at the time of surgery was 68 years (46-77) (Table 1). The median size of the largest tumor(s) resected was 2.75 cm (1.5-5.5 cm) and second largest tumor(s) was 1.75 cm (1.0-4.0 cm). Four patients underwent bilateral staged PN and one patient underwent simultaneous bilateral PN (horseshoe kidney). Two patients underwent RFA at the time of biopsy of the contralateral mass after PN. Five patients underwent CT-bx/FNA (5/5) of the contralateral mass followed by active surveillance. Mean follow up was 34 months. There was no significant change in median creatinine pre- and post-operatively. One patient was lost to follow up and one patient died of unknown causes 5 years post-operatively. eGFR decreased an average of 16.96% post-operatively, including a single patient whose eGFR increased by 7.8% after surgery and a single patient whose eGFR did not change (Table 2)., Conclusions: Patients with bilateral renal masses and pathologically proven RO can be safely managed with active surveillance after biopsy confirmation of the contralateral mass.

Bochdalek hernia is a congenital defect in the diaphragm posterolaterally that allows abdominal contents to enter the thorax. Herniation and development of an intrathoracic kidney associated with this condition are uncommon, with an incidence less than 0.25%. Intrathoracic kidney is also the rarest form of renal ectopia, consisting of less than 5% of cases. We present a series of images from a case of a 55-year-old female with a right renal mass suspicious for malignancy in a solitary right intrathoracic kidney within Bochdalek hernia, who underwent an open right partial nephrectomy for definitive diagnosis and treatment., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To evaluate the outcome of patients after surgical resection of isolated retroperitoneal lymph node (RPLN) recurrence of renal cell carcinoma (RCC) using a multicentre international cohort., Patients and Methods: In all, 50 patients were identified who underwent resection of isolated RPLN recurrence of RCC at four institutions after nephrectomy for pTany Nany M0 disease. Progression-free (PFS) and cancer-specific survival (CSS) were estimated using the Kaplan-Meier method. Cox proportional hazards regression models were used to assess the association of clinicopathological characteristics with disease progression., Results: The median (interquartile range, IQR) age at resection was 57.0 (50.0-62.5) years. The median (IQR) time to RPLN recurrence after nephrectomy was 12.6 (6.9-39.5) months, with no significant difference in median time to RPLN recurrence between patients with N+ disease at nephrectomy (10.7 [6.5-24.6] months) and those with Nx/pN0 disease at nephrectomy (13.7 [8.7-44.2] months) (P = 0.66). The median (IQR) size of the RPLN recurrence before resection was 2.6 (1.9-5) cm. The most common site for RPLN recurrence was within the interaortocaval region (34%). The median (IQR) follow-up after RPLN resection for patients alive at last follow-up was 28.0 (13.7-51.2) months. During follow-up, 26 patients developed RCC recurrence, at a median (IQR) of 9.9 (4.0-18.5) months after RPLN resection. Of those who developed a secondary recurrence, disease was again isolated to the retroperitoneum in seven patients. In all, 11 patients subsequently died, including 10 who died from disease. The median PFS after RPLN resection was 19.5 months, with a 3- and 5-year PFS of 40.5% and 35.4%, respectively. We also found that RPLN recurrence at ≤12 months after nephrectomy was associated with a significantly inferior median PFS (12.3 months) compared with RPLN recurrence at >12 months after nephrectomy (47.6 months; P = 0.003). Moreover, on multivariate analysis, a shorter time to recurrence remained associated with a significantly increased risk for subsequent disease progression (hazard ratio 3.51; P = 0.005)., Conclusion: Surgical resection of isolated RPLN recurrence from RCC may result in durable cancer control in appropriately selected patients. Recurrence at ≤12 months after nephrectomy was associated with a significantly increased risk of progression after resection, underscoring the importance of this variable for risk stratification. Thus, we recommend that, in the setting of isolated RPLN recurrence of RCC (in patients without precluding comorbidities), careful consideration with the patients and medical oncology colleagues be undertaken about the relative and individualised benefits of surgical resection, systemic therapy, and surveillance., (© 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.)

Background: Renal-cell carcinoma is highly vascular, and proliferates primarily through dysregulation of the vascular endothelial growth factor (VEGF) pathway. We tested sunitinib and sorafenib, two oral anti-angiogenic agents that are effective in advanced renal-cell carcinoma, in patients with resected local disease at high risk for recurrence., Methods: In this double-blind, placebo-controlled, randomised, phase 3 trial, we enrolled patients at 226 study centres in the USA and Canada. Eligible patients had pathological stage high-grade T1b or greater with completely resected non-metastatic renal-cell carcinoma and adequate cardiac, renal, and hepatic function. Patients were stratified by recurrence risk, histology, Eastern Cooperative Oncology Group (ECOG) performance status, and surgical approach, and computerised double-blind randomisation was done centrally with permuted blocks. Patients were randomly assigned (1:1:1) to receive 54 weeks of sunitinib 50 mg per day orally throughout the first 4 weeks of each 6 week cycle, sorafenib 400 mg twice per day orally throughout each cycle, or placebo. Placebo could be sunitinib placebo given continuously for 4 weeks of every 6 week cycle or sorafenib placebo given twice per day throughout the study. The primary objective was to compare disease-free survival between each experimental group and placebo in the intention-to-treat population. All treated patients with at least one follow-up assessment were included in the safety analysis. This trial is registered with ClinicalTrials.gov, number NCT00326898., Findings: Between April 24, 2006, and Sept 1, 2010, 1943 patients from the National Clinical Trials Network were randomly assigned to sunitinib (n=647), sorafenib (n=649), or placebo (n=647). Following high rates of toxicity-related discontinuation after 1323 patients had enrolled (treatment discontinued by 193 [44%] of 438 patients on sunitinib, 199 [45%] of 441 patients on sorafenib), the starting dose of each drug was reduced and then individually titrated up to the original full doses. On Oct 16, 2014, because of low conditional power for the primary endpoint, the ECOG-ACRIN Data Safety Monitoring Committee recommended that blinded follow-up cease and the results be released. The primary analysis showed no significant differences in disease-free survival. Median disease-free survival was 5·8 years (IQR 1·6-8·2) for sunitinib (hazard ratio [HR] 1·02, 97·5% CI 0·85-1·23, p=0·8038), 6·1 years (IQR 1·7-not estimable [NE]) for sorafenib (HR 0·97, 97·5% CI 0·80-1·17, p=0·7184), and 6·6 years (IQR 1·5-NE) for placebo. The most common grade 3 or worse adverse events were hypertension (105 [17%] patients on sunitinib and 102 [16%] patients on sorafenib), hand-foot syndrome (94 [15%] patients on sunitinib and 208 [33%] patients on sorafenib), rash (15 [2%] patients on sunitinib and 95 [15%] patients on sorafenib), and fatigue 110 [18%] patients on sunitinib [corrected]. There were five deaths related to treatment or occurring within 30 days of the end of treatment; one patient receiving sorafenib died from infectious colitis while on treatment and four patients receiving sunitinib died, with one death due to each of neurological sequelae, sequelae of gastric perforation, pulmonary embolus, and disease progression. Revised dosing still resulted in high toxicity., Interpretation: Adjuvant treatment with the VEGF receptor tyrosine kinase inhibitors sorafenib or sunitinib showed no survival benefit relative to placebo in a definitive phase 3 study. Furthermore, substantial treatment discontinuation occurred because of excessive toxicity, despite dose reductions. These results provide a strong rationale against the use of these drugs for high-risk kidney cancer in the adjuvant setting and suggest that the biology of cancer recurrence might be independent of angiogenesis., Funding: US National Cancer Institute and ECOG-ACRIN Cancer Research Group, Pfizer, and Bayer., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Unlabelled: In an analysis of a large single-institution experience in the surgical management of renal cell carcinoma (RCC) and inferior vena cava (IVC) thrombus, the authors present the effect of RCC characteristics on survival, and aim to identify potential preoperative variables predictive of intraoperative complexity with regard to estimated blood loss, transfusion volume, surgical time, length of stay, and postoperative complication rates. Age, American Society of Anesthesiologists score, Charlson Comorbidity Index, preoperative calcium, preoperative creatinine, and IVC wall invasion were significantly related to complication rates., Introduction: Preoperative laboratory values are commonly used as markers of health and potential disease burden, however, their effect on perioperative complexity has not previously been assessed. The authors aimed to evaluate the effect of renal cell carcinoma and inferior vena cava (IVC) thrombus characteristics on cancer-specific survival (CSS), and identify potential preoperative variables predictive of intraoperative complexity., Materials and Methods: In a retrospective chart review we identified 144 patients who underwent nephrectomy and IVC thrombectomy. Univariate and multivariate analyses were used to assess the effect of disease characteristics on CSS and postoperative complications. Linear regression analysis was used to determine the association between preoperative laboratory values and intraoperative complexity characterized by estimated blood loss (EBL), transfusion volume (TV), operative time, and length of hospital stay (LOS)., Results: Analysis of intraoperative complexity revealed a significant correlation between preoperative creatinine (Cr) and EBL (P = .022), TV (P = .041), and LOS (P = .005), and preoperative hemoglobin (Hgb) was associated with increased EBL (P < .001) and TV (P < .001). Multivariate analyses showed a significant relationship between overall complication rates and preoperative calcium (Ca; P = .012), American Society of Anesthesiologists (ASA) score (P = .003), and IVC wall invasion (P = .005), and a significant association between major complications and preoperative Ca (P = .011), preoperative Cr (P = .041), age (P = .050), and Charlson Comorbidity Index (CCI; P = .002)., Conclusion: With regard to intraoperative complexity and postoperative complications, preoperative Cr and Hgb were significantly associated with increased EBL, TV, and LOS, and ASA score, preoperative Ca, preoperative Cr, IVC wall invasion, age, and CCI were found to have significant relationships with complication rates., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Management of renal cell carcinoma (RCC) with inferior vena cava thrombus (IVCT) is associated with high morbidity. Chronic kidney disease (CKD) is a known risk factor for perioperative complications in many surgical procedures. The objective of this study was to review the association between preoperative CKD (eGFR < 60 mL/min) and post-operative outcomes in patients with RCC and IVCT undergoing radical nephrectomy (RN) and tumour thrombectomy (TT)., Methods: A retrospective review of patients with RCC and IVCT treated with RN and TT was carried out. Complications were recorded according to the Clavien-Dindo classification. Multivariable models were fitted using logistic regression analyses for high-grade complications and salvage therapies and linear-regression for intraoperative blood loss (IBL)., Results: One hundred and one patients with RCC and IVCT, treated with RN and TT, were identified. Forty per cent of patients had preoperative CKD. Median IBL was higher in CKD arm (2.5 versus 1.6 L, P = 0.04). In a multivariate linear regression analysis, CKD (beta 1.34, P = 0.01) remained an independent predictor of IBL. High-grade complications were more frequent in the CKD group (34% versus 16%, P = 0.09) and in logistic regression analysis, CKD was an independent predictor of high-grade complications (OR 3.33, 95% CI 1.01-10.9). Furthermore, CKD patients were less likely to be considered for salvage therapies (62% versus 38%, P = 0.02)., Conclusions: In patients treated with RN and TT, CKD is an independent predictor of perioperative morbidity. This clinical variable should be considered when selecting patients and subsequent efforts should be made to optimize other competing risk factors in order to reduce the incidence of perioperative adverse events in this patient population., (© 2015 Royal Australasian College of Surgeons.)

PAX8 is a transcription factor involved in the regulation of organogenesis of the thyroid gland, kidney, and Müllerian system. It is commonly expressed in epithelial tumors of thyroid and parathyroid glands, kidney, thymus, and female genital tract. PAX8 is increasingly used in the establishment of tissue of origin in carcinomas and has recently been identified in a subset of small blue round cell tumors including Ewing sarcomas/PNETs. However, it is unclear if this association in ES/PNETs is due to renal origin or is PNET specific. In this study we investigated the PAX8 staining pattern of primary renal and extra-renal ES/PNETs to explore its potential diagnostic and prognostic role. A tissue microarray (TMA) of 22 cases of extra-renal Ewing/PNETs and two separate cases of primary renal PNET whole slide sections were immunohistochemically stained with rabbit polyclonal PAX8 antibody. PAX8 was positive in 2 of 2 primary renal PNETs and in 14 (64 %) cases of the extra renal PNETs. The association between PAX8 immunoreactivity and Ewing/PNET was identified in both primary renal and extra-renal Ewing/PNETs for the first time. Further studies are warranted to verify these findings and to shed light in the tumorigenesis of Ewing/PNET. However, PAX8 is not useful in establishing a diagnosis of Ewing/PNET due to its presence in different tumors like carcinomas, lymphomas and sarcomas. PAX8 does not seem to have prognostic value.

Purpose: To determine if patients with renal cell carcinoma (RCC) with levels III and IV tumor thrombi are receive any reduction in complication rate utilizing veno-venous bypass (VVB) over cardiopulmonary bypass (CPB) for high level (III/IV) inferior vena cava (IVC) tumor thrombectomy and concomitant radical nephrectomy., Materials and Methods: From May 1990 to August 2011, we reviewed 21 patients that had been treated for RCC with radical nephrectomy and concomitant IVC thrombectomy employing either CPB (n =16) or VVB (n=5). We retrospectively reviewed our study population for complication rates and perioperative characteristics., Results: Our results are reported using the validated Dindo-Clavien Classification system comparing the VVB and CPB cohorts. No significant difference was noted in minor complication rate (60.0% versus 68.7%, P=1.0), major complication rate (40.0% versus 31.3%, P=1.0), or overall complication rate (60.0% versus 62.5%, P=1.0) comparing VVB versus CPB. We also demonstrated a trend towards decreased time on bypass (P=0.09) in the VVB cohort., Conclusion: The use of VVB over CPB provides no decrease in minor, major, or overall complication rate. The use of VVB however, can be employed on an individualized basis with final decision on vascular bypass selection left to the discretion of the surgeon based on specifics of the individual case.

Objective: To assess the pattern of renal cell carcinoma (RCC) recurrences in nephron-sparing surgery (NSS) patients, and to determine whether current guidelines for surveillance could be modified based on such patterns., Methods: Retrospective review of a single-institution NSS database. Pattern of RCC recurrences and factors associated with recurrence were analyzed using univariate and multivariable competing risk regression analyses. Cost of surveillance was estimated based on Medicare charges., Results: A total of 505 patients underwent elective NSS for RCC. Pathologic T stage included 394 pT1a and 79 pT1b lesions. Median follow-up was 38.3 (6-88) months. Recurrence was detected in 26 patients (5.1%) at a median of 18.9 months (2.7% pT1a and 12.7% pT1b). The estimated 5-year cumulative incidence of recurrence for unifocal pT1a lesions was 2.7%. On multivariable analysis, stage higher than pT1a (HR, 5.56 [CI. 2.57-12.0]) and the presence of multifocal or bilateral tumors (HR, 3.32 [CI, 1.45-7.61]) were independent predictors of disease recurrence. For the entire cohort, recurrence was observed in only 10 patients beyond 24 months including only 2 cases with pT1a., Conclusion: Current guidelines adequately capture most clinically significant recurrences, and with longer follow-up, it may be possible to confirm that routine surveillance beyond 2 years may have little clinical significance for patients with asymptomatic unifocal pT1a., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: Cytoreductive nephrectomy (CN) is a therapeutic consideration in patients with metastatic renal cell carcinoma (mRCC). We hypothesized that sarcopenia, a novel marker of nutritional status, is a predictor of survival after CN., Materials and Methods: Of 105 patients who underwent CN at our institution for mRCC, 93 had preoperative imaging available for analysis. Skeletal muscle index was calculated on axial images at the third lumbar vertebrae, and a threshold skeletal muscle index of<43 cm(2)/m(2) in men with a body mass index (BMI)<25 kg/m(2),<53 cm(2)/m(2) in men with a BMI>25 kg/m(2), and<41 cm(2)/m(2) in women was used to classify patients as sarcopenic vs. nonsarcopenic. This classification was then retrospectively correlated with overall survival (OS)., Results: Overall, 27 patients (29.0%) had sarcopenia before surgery. Sarcopenic patients received neoadjuvant systemic therapy more often (P = 0.022), had lower BMI (P = 0.001), had a higher incidence of hypoalbuminemia before surgery (P = 0.035), received more blood transfusions perioperatively (P = 0.006) owing to lower preoperative hemoglobin levels (P = 0.001), and had longer length of stay after surgery (P = 0.02). Median OS in sarcopenic patients was 7 months (95% CI: 0.8-13.2) vs. 23 months (95% CI: 12.4-33.6) in nonsarcopenic patients. On multivariate analysis, sarcopenia was an independent predictor of OS (hazard ratio = 2.13, 95% CI: 1.15-3.92; P = 0.016) in addition to number of metastatic sites>2 (hazard ratio = 2.09, 95% CI: 1.24-3.53; P = 0.006)., Conclusions: Sarcopenia can be an important prognostic factor associated with worse OS after CN for mRCC., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Minimally invasive surgical techniques have revolutionized the surgical management of kidney cancer. Current evidence suggests that the surgical developments gained by traditional laparoscopy have been advanced by the robotic platform, particularly as it has been applied to techniques for nephron preservation., Methods: The medical literature from peer-reviewed journals was reviewed to evaluate the feasibility and efficacy of robotic-assisted surgery in the management of renal cell carcinoma. Particular attention was paid to studies comparing robotic-assisted surgery with more traditional surgical techniques. In this review, we have highlighted the evolution of robotic assistance for renal surgery as it pertains to renal oncology. The differing approaches to standard surgeries are discussed as well as current trends to improve perioperative outcomes.In addition, we have reviewed the application of robotic assistance to more complex cases and highlight technological advancements that have pushed the boundaries of surgical care., Results: Robotic-assisted renal surgery is effective for appropriately selected patients. Robotic-assisted radical nephrectomy provides equivalent outcomes to traditional open and laparoscopic approaches, albeit with added financial burden. Robotic-assisted partial nephrectomy - through either transperitoneal or retroperitoneal access - can provide superior outcomes to laparoscopic approaches due to several technical advantages,including improved instrument articulation., Conclusions: Robotic assistance has transformed the delivery of surgical care to the patient with renal cell carcinoma. For renal surgery, morbidity and patient satisfaction are potentially improved when using robotic platforms compared with open and traditional laparoscopic approaches without compromising oncological control, and this is particularly true for nephron-sparing surgery.

Background: The objective of this study was to determine if the percentage of sarcomatoid differentiation (%Sarc) in renal cell carcinoma (RCC) can be used for prognostic risk stratification, because sarcomatoid RCC (sRCC) is an aggressive variant of kidney cancer., Patients and Methods: We performed a retrospective analysis of patients who underwent surgery for RCC at our institution between 1999 and 2012. Pathology slides for all sRCC cases were reexamined by a single pathologist and %Sarc was calculated. %Sarc was analyzed as a continuous variable and as a categorical variable at cut points of 5%, 10%, and 25%. Potential prognostic factors associated with overall survival (OS) were determined using the Cox regression model. OS curves were generated using Kaplan-Meier methods and survival differences compared using the log-rank test., Results: One thousand three hundred seven consecutive cases of RCC were identified, of which 59 patients had sRCC (4.5%). As a continuous variable %Sarc was inversely associated with OS (P = .023). Predictors of survival on multivariable analysis included pathologic (p) T status, tumor size, clinical (c) M status and %Sarc at the 25% level. OS was most dependent on the presence of metastatic disease (4 months vs. 21.2 months; P = .001). In cM0 patients with locally advanced (≥ pT3) tumors, OS was significantly diminished in patients with > 25 %Sarc (P = .045). However, %Sarc did not influence OS in patients with cM1 disease., Conclusion: Patients with sRCC have a poor overall outcome as evidenced by high rates of recurrence and death, indicating the need for more effective systemic therapies. In nonmetastatic patients, the incorporation of %Sarc in predictive nomograms might further improve risk stratification., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: Surgery for renal cell carcinoma with tumor thrombus has a high potential morbidity rate, and the current classification system based on proximal tumor thrombus level (TTL) has not been shown to consistently predict outcomes., Aim: To assess the prognostic value of inferior vena cava tumor thrombus volume (IVC-TV) for determining the perioperative complications as well as with survival end points., Methods: From June 2001 to June 2012, we identified 147 patients who underwent radical nephrectomy with venous thrombi. In total, 66 patients had IVC involvement and available imaging for review. IVC-TV was measured by cross-sectional area and height measurement for each axial slice. Linear, logistic models and Cox proportional hazard was used for analysis., Results: Median IVC-TV was 16.5 cm(3), and 18 patients had TTL≥III. In total, 57 Clavien I-V complications were documented in 32 patients including 3 deaths. On multivariate analysis, age>65 years, American Society of Anesthesiologists>3, and IVC-TV>15 cm(3) were independent predictors for perioperative complications. Disease progression (PoD) occurred in 78% of patients, and metastatic disease (hazard ratio [HR] = 3.33, P<0.01) and non-clear cell histology (HR = 2.98, P = 0.02) were independent predictors of PoD. Median time to death was 16 months (interquartile range: 5.2-42.9). On Cox regression analysis, metastatic disease, non-clear cell histology, IVC-TV>15 cm(3), and TTL III/IV were significantly associated with overall survival. As a preoperative variable, IVC-TV>15 cm(3) was shown to be an independent predictor of PoD (HR = 2.3, P = 0.01) and overall survival (HR = 2.21, P = 0.03)., Conclusion: IVC-TV has value as a prognostic indicator, which is superior to TTL in the setting of renal cell carcinoma with IVC venous thrombus., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To assess the oncologic and functional outcomes of salvage renal surgery following failed primary intervention for RCC., Materials and Methods: We performed a retrospective review of patients who underwent surgery for suspected RCC during 2004-2012. We identified 839 patients, 13 of whom required salvage renal surgery. Demographic data was collected for all patients. Intraoperative and postoperative data included ischemic duration, blood loss and perioperative complications. Preoperative and postoperative assessments included abdominal CT or magnetic resonance imaging, chest CT and routine laboratory work. Estimated glomerular filtration rate (eGFR) was calculated according to the Modification of Diet in Renal Disease equation., Results: The majority (85%) of the patients were male, with an average age of 64 years. Ten patients underwent salvage partial nephrectomy while 3 underwent salvage radical nephrectomy. Cryotherapy was the predominant primary failed treatment modality, with 31% of patients undergoing primary open surgery. Pre-operatively, three patients were projected to require permanent post-operative dialysis. In the remaining 10 patients, mean pre- and postoperative serum creatinine and eGFR levels were 1.35 mg/dL and 53.8 mL/min/1.73 m2 compared to 1.43 mg/dL and 46.6 mL/min/1.73 m2, respectively. Mean warm ischemia time in 10 patients was 17.4 min and for all patients, the mean blood loss was 647 mL. The predominant pathological stage was pT1a (8/13; 62%). Negative surgical margins were achieved in all cases. The mean follow-up was 32.9 months (3.5-88 months)., Conclusion: While salvage renal surgery can be challenging, it is feasible and has adequate surgical, functional and oncological outcomes.

Purpose: To compare retrograde dye injection through an externalized ureteral catheter with direct needle injection of dye into proximal ureter for identification of unrecognized collecting system disruption and integrity of subsequent repair during open partial nephrectomy., Materials and Methods: We retrospectively reviewed the records of 259 consecutive patients who underwent open partial nephrectomy. Externalized ureteral catheters were placed preoperatively in 110 patients (Group 1); needle injection of methylene blue directly into proximal ureter was used in 120 patients (Group 2). No assessment of the collecting system was performed in 29 patients (Group 3). We compared intraoperative parameters, tumor characteristics, collecting system entry and incidence of urine leaks among the three groups., Results: The mean tumor diameter was 3.1 cm in Group 1, 3.6cm in Group 2, and 3.8 cm in Group 3 (p = 0.04); mean EBL 320cc, 351 cc and 376cc (p = 0.5); mean operative time 193.5 minutes, 221 minutes and 290 minutes (p < 0.001). Collecting system entry was recognized in 63%, 76% and 38% of cases in Groups 1, 2 and 3 respectively. (p = 0.07). Postoperative urine leaks requiring some form of management occurred in 11 patients from group 1 and 6 from group 2. (p = 0.2). No patient in Group 3 developed a urinary leak., Conclusions: Identification of unrecognized collecting system disruption as well as postoperative urine leak rate in patients undergoing partial nephrectomy were not influenced by the intraoperative technique of identifying unrecognized collecting system entry. Postoperative urine leaks are uncommon despite recognized collecting system disruption in the majority of patients.

Purpose: We report a multicenter international cohort representing what is to our knowledge the largest surgical experience with managing isolated retroperitoneal nodal recurrence of renal cell carcinoma, a unique subset of locoregional disease, yet to be described in detail., Materials and Methods: Patients with isolated nodal recurrence of pTanyN+M0 disease after nephrectomy were identified by retrospective chart review at 3 independent institutions. Progression-free survival was estimated by the Kaplan-Meier method and used to compare survival outcomes between primary T(1-2)N(any)M0 and T3N(any)M0 tumors as well as clear cell and nonclear cell histology renal cell carcinoma., Results: A total of 22 patients met study inclusion criteria. Median time to local postoperative recurrence was 31.5 months (IQR 12.9-43.3). After resection of isolated nodal recurrence 10 patients (46%) had a secondary recurrence at a median of 11.2 months (IQR 8.1-18.4), of whom 2 (9%) died of the disease. Overall median progression-free survival was 12.7 months, including 24.8 months for T(1-2)N(any)M0 tumors, 9.9 months for T3N(any)M0 tumors, and 13.4 and 17.6 months for clear and nonclear cell renal cell carcinoma, respectively., Conclusions: Surgical resection represents the best curative option for patients who present with isolated retroperitoneal lymph node recurrence of renal cell carcinoma. Durable postoperative progression-free survival is attainable in many patients regardless of histology or clinical TNM stage. In addition, our cohort showed a lower renal cell carcinoma related mortality rate than in previous series of local metastasis. As such, all patients free of precluding comorbidities should be considered candidates for complete surgical resection performed by an experienced genitourinary surgeon., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Since the advent of the first standardized renal tumor complexity system, many subsequent scoring systems have been introduced, many of which are complicated and can make it difficult to accurately measure data end points. In light of these limitations, we introduce the new zonal NePhRO scoring system., Patients and Methods: The zonal NePhRO score is based on 4 anatomical components that are assigned a score of 1, 2, or 3, and their sum is used to classify renal tumors. The zonal NePhRO scoring system is made up of the (Ne)arness to collecting system, (Ph)ysical location of the tumor in the kidney, (R)adius of the tumor, and (O)rganization of the tumor. In this retrospective study, we evaluated patients exhibiting clinical stage T1a or T1b who underwent open partial nephrectomy performed by 2 genitourinary surgeons. Each renal unit was assigned both a zonal NePhRO score and a RENAL (radius, exophytic/endophytic properties, nearness of tumor to the collecting system or sinus in millimeters, anterior/posterior, location relative to polar lines) score, and a blinded reviewer used the same preoperative imaging study to obtain both scores. Additional data points gathered included age, clamp time, complication rate, urine leak rate, intraoperative blood loss, and pathologic tumor size., Results: One hundred sixty-six patients underwent open partial nephrectomy. There were 37 perioperative complications quantitated using the validated Clavien-Dindo system; their occurrence was predicted by the NePhRO score on both univariate and multivariate analyses (P = .0008). Clinical stage, intraoperative blood loss, and tumor diameter were all correlated with the zonal NePhRO score on univariate analysis only., Conclusion: The zonal NePhRO scoring system is a simpler tool that accurately predicts the surgical complexity of a renal lesion., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Unlabelled: Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Little is known about the prognostic impact of body mass index (BMI) and obesity on patients with locally advanced kidney cancer. Previous studies suggest that clinical/pathological stage, the proximal extent of the tumour thrombus, direct vascular wall invasion, and preoperative performance status may all constitute important prognostic factors within this patient population. The present study shows that a patient's metastatic status, higher level of tumour thrombus, and lower BMI all constitute adverse predictors of overall survival in patients who have RCC with inferior vena cava tumour thrombus., Objective: •  To determine which clinical variables, including body mass index (BMI), predict overall survival (OS) after nephrectomy with inferior vena cava (IVC) thrombectomy for renal cell carcinoma (RCC) with tumour thrombus., Patients and Methods: •  After institutional review board approval, a retrospective analysis of all patients (N= 100) undergoing nephrectomy and IVC thrombectomy for RCC from 1989 to 2010 were reviewed. One patient was excluded owing to missing clinical information leaving 99 patients in the study cohort. •  Patients were placed into one of two subgroups, based on their preoperative BMI (BMI ≤30 kg/m(2) or BMI >30 kg/m(2) ). •  Complications, blood loss, level of tumour thrombus, side of tumour and follow-up data were tabulated., Results: •  Fifty-six patients had a BMI ≤30 kg/m(2) and 43 patients had a BMI >30 kg/m(2) . Intraoperative complications occurred in 14% of those with BMI >30 kg/m(2) and 5.4% of those with a BMI ≤30 kg/m(2) (P= 0.171). •  On multivariate analysis, a higher thrombus level (III/IV vs I/II) and the presence of metastatic disease at time of diagnosis was associated with a worse OS (P= 0.041 and P < 0.001, respectively). •  The subgroup with a higher preoperative BMI had a significantly better OS (hazard ratio 0.42; 95% confidence interval 0.22-0.80, P= 0.009). •  Similarly, our Kaplan-Meier survival analysis showed an improved OS in the patient cohort with a BMI >30 kg/m(2) (P= 0.016)., Conclusion: •  Important predictors of outcome in patients undergoing nephrectomy with IVC thrombectomy for RCC with tumour thrombus include preoperative BMI, level of IVC tumour thrombus, and metastatic status at time of surgery., (© 2012 BJU INTERNATIONAL.)

Unlabelled: What's known on the subject? and What does the study add? Historically, the surgical management of renal tumours with intravascular tumour thrombus has been associated with high morbidity and mortality. In addition, few cases are treated, and typically at tertiary care referral centres, hence little is known and published about the ideal surgical management of such complex cases. The present comprehensive review details how a multidisciplinary surgical approach to renal tumours with intravascular tumour thrombus can optimise patient outcomes. Similarly, we have developed a treatment algorithm in this review that can be used in the surgical planning of such cases., Objectives: To detail the perioperative and technical considerations essential to the surgical management of renal cell carcinoma (RCC) with inferior vena cava (IVC) tumour thrombus, as historically patients with RCC and IVC tumour thrombus have had an adverse clinical outcome. • Recent surgical and perioperative advances have for the most part optimized the clinical outcome of such patients., Materials and Methods: A comprehensive review of the scientific literature was conducted using MEDLINE from 1990 to present using as the keywords 'renal cell carcinoma' and 'IVC tumor thrombus'. • In all, 62 manuscripts were reviewed, 58 of which were in English. Of these, 25 peer-reviewed articles were deemed of scientific merit and were assessed in detail as part of this comprehensive review. • These articles consist of medium to large (≥25 patients) peer-reviewed studies containing contemporary data pertaining to the surgical management of RCC and IVC tumour thrombus. • Many of these studies highlight important surgical techniques and considerations in the management of such patients and report on their respective clinical outcomes., Results: Careful preoperative planning is essential to optimising the outcomes within this patient cohort. High quality and detailed preoperative imaging studies help delineate the proximal extension of the IVC tumour thrombus and possible caval wall direct invasion while determining the potential necessity for intraoperative vascular bypass. • The surgical management of RCC and IVC tumour thrombus (particularly for level III or IV) often requires the commitment of a multidisciplinary surgical team to optimise patient surgical outcomes. • Despite significant improvements in surgical techniques and perioperative care, the 5-year overall survival remains only between 32% and 69%, highlighting the adverse prognosis of such locally advanced tumours. • Important prognostic factors within this patient cohort include pathological stage, nuclear grade, tumour histology, lymph node and distant metastatic status, preoperative performance status, Charlson comorbidity index, and nutritional status., Conclusions: The multidisciplinary surgical care of RCC and IVC tumour thrombus (particularly high level thrombi) is pivotal to optimising the surgical outcome of such patients. • Similarly, important preoperative, perioperative, and postoperative considerations can improve the surgical outcome of patients., (© 2012 BJU INTERNATIONAL.)

Objective: To determine the reliability of the RENAL nephrometry scoring system by studying its reproducibility among different observers., Methods: We reviewed computed tomography or magnetic resonance imaging scans from 51 patients who underwent partial nephrectomy at our cancer center. Digitized axial and coronal images were available for all patients. Three surgeons independently scored the renal tumors using the RENAL nephrometry system. The scoring system had 5 components: R (tumor diameter), E (exophytic/endophytic), N (nearness to collecting system), A (anterior/posterior), and L (location in relation to polar lines). Interobserver variability was calculated for each of the 5 components using a frequency procedure and Kappa statistics., Results: The reliability assessed by frequency procedure showed concordance among 3 observers in 94%, 76%, 66%, 80%, and 54% for the R, E, N, A, and L components, respectively. The corresponding kappa values for each of these 5 components were 0.95, 0.86, 0.76, 0.84, and 0.73, respectively., Conclusion: The RENAL nephrometry scoring system has good interobserver reliability. Quantifying the tumor location (L) was more challenging and the least reliable of the 5 components. This variation might affect the total nephrometry score and should be considered when using the system to compare different series of patients undergoing partial nephrectomy., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objectives: Patients with genitourinary tumors and inferior vena cava thrombus often have large lesions and significant neovascularity. Early division of the renal vein with the in situ thrombus is desirable; however, concerns have been raised regarding tumor spillage and thrombus migration. We describe a novel technique using a stapling device to secure the renal vein during resection of renal tumors associated with an inferior vena cava thrombus., Methods: Since 2005, 38 patients have undergone surgery for genitourinary tumors and inferior vena cava tumor thrombus by a single surgeon. We examined the utility of an endovascular stapler (Endo-GIA) to transect the renal vein and the in situ thrombus. The renal vein containing the tumor thrombus was divided with an endovascular stapler in 14 of 38 patients. The outcomes of this technique were assessed., Results: The stapled group included more level III-IV thrombi than the nonstapled group. The tumors removed in the stapled group were larger (median 11.5 versus 9 cm), and the median intraoperative transfusion requirements were greater (9.5 versus 3 U). One patient developed an intraoperative pulmonary embolus, and another experienced hemodynamic changes suggestive of an embolus. Local recurrence developed in 1 and 2 patients in the stapled and conventional groups, respectively, during a median follow-up period of 3 months., Conclusions: The Endo-GIA stapler is a safe and effective instrument for division of the in situ renal vein component of the tumor thrombus, allowing the surgeon to complete the nephrectomy, achieve hemostasis, and, subsequently, concentrate on the vena cava and tumor thrombus aspects of the procedure., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To report the functional and oncological outcome of nephron-sparing surgery (NSS) for pathological stage pT3bNxMx (2002 Tumour-Node-Metastasis staging) renal cell carcinoma (RCC) with tumour thrombus confined to the renal vein., Patients and Methods: Of the 305 patients who underwent NSS at our institute from October 2004 to July 2009, seven (2%) were found to have stage T3bNxMx RCC on final pathology. Their charts were reviewed to identify demographic, operative and pathology details of these patients, in addition to obtaining functional and oncological outcome data., Results: All seven patients had centrally located endophytic tumours. There were absolute indications for NSS in six patients (solitary kidney in five, renal insufficiency in one). The clinical stage was T1a in five and T3b in two patients; in those with cT1a, thrombus was first identified with intraoperative ultrasonography in two and by palpation of the renal vein or during the NSS in the remaining three. Renal surface hypothermia was applied in four cases (mean 77 min) and warm ischaemia in three (mean 38 min). The mean (range) tumour size was 3.9 (2.5-6) cm and all the tumours were clear cell RCC on histology, and all had negative surgical margins. The mean estimated glomerular filtration rate (eGFR) decreased by 24% after surgery. One patient developed new-onset renal failure (eGFR < 30 mL/min/1.73 m(2) ). Postoperative urine leak occurred in one patient successfully managed with a JJ stent. One patient developed a local recurrence with level III inferior vena caval (IVC) tumour thrombus 9 months after NSS and was managed with radical excision and IVC thrombectomy followed by postoperative dialysis. Six other patients were free of recurrence with no need for dialysis at a mean follow-up of 30 months., Conclusions: In selected patients with pathological stage T3b RCC and tumour thrombus confined to the renal vein, NSS is a feasible treatment option with acceptable oncological and renal functional outcomes., (© 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.)

Background: Renal cell carcinoma accounts for approximately 3% of adult malignancies and over 90% of primary renal tumors. Recurrence rates for patients with locally advanced renal cell carcinoma (LARCC) remain high., Methods: The authors review literature regarding prognostic factors, potential biomarkers, surgical strategies, and adjuvant therapy trials for patients with LARCC., Results: Molecular tumor markers may improve existing staging systems for predicting prognosis. Surgery is the best initial treatment for most patients with clinically localized renal tumors, although complete surgical resection can be challenging for patients with large tumors, bulky regional lymph node involvement, or inferior vena cava tumor thrombus. Significant recurrence rates for patients with LARCC undergoing nephrectomy indicate the presence of undetected micrometastases at the time of surgery. Adjuvant radiation, chemotherapy, and immunotherapy have been ineffective. Other trials of adjuvant therapy are ongoing., Conclusions: Aggressive surgical resection alone for LARCC is not sufficient to prevent disease recurrence in a significant number of patients. Adjuvant therapies are needed to improve cancer-specific survival.

Renal cell carcinoma metastatic to the prostate is a rare entity. We report a delayed (9 years) metachronous solitary metastasis presentation of renal cell carcinoma to the prostate. Including our patient, only 5 cases of metastatic renal cell carcinoma to the prostate have been reported. Four patients presented with hematuria and two with bladder outlet obstruction; one had an incidental finding after prostate biopsy. Radical prostatectomy could be considered for patients with the prostate as the only site of disease.