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Background: In-hospital mortality and complication rates after partial and radical nephrectomy in patients with history of heart-valve replacement are unknown., Patients and Methods: Relying on the National Inpatient Sample (2000-2019), kidney cancer patients undergoing partial or radical nephrectomy were stratified according to presence or absence of heart-valve replacement. Multivariable logistic and Poisson regression models addressed adverse hospital outcomes., Results: Overall, 39,673 patients underwent partial nephrectomy versus 94,890 radical nephrectomy. Of those, 248 (0.6%) and 676 (0.7%) had a history of heart-valve replacement. Heart-valve replacement patients were older (median partial nephrectomy 69 versus 60 years; radical nephrectomy 71 versus 63 years), and more frequently exhibited Charlson comorbidity index ≥ 3 (partial nephrectomy 22 versus 12%; radical nephrectomy 32 versus 23%). In partial nephrectomy patients, history of heart-valve replacement increased the risk of cardiac complications [odds ratio (OR) 4.33; p < 0.001), blood transfusions (OR 2.00; p < 0.001), intraoperative complications (OR 1.53; p = 0.03), and longer hospital stay [rate ratio (RR) 1.25; p < 0.001], but not in-hospital mortality (p = 0.5). In radical nephrectomy patients, history of heart-valve replacement increased risk of postoperative bleeding (OR 4.13; p < 0.001), cardiac complications (OR 2.72; p < 0.001), intraoperative complications (OR 1.53; p < 0.001), blood transfusions (OR 1.27; p = 0.02), and longer hospital stay (RR 1.12; p < 0.001), but not in-hospital mortality (p = 0.5)., Conclusions: History of heart-valve replacement independently predicted four of twelve adverse outcomes in partial nephrectomy and five of twelve adverse outcomes in radical nephrectomy patients including intraoperative and cardiac complications, blood transfusions, and longer hospital stay. Conversely, no statistically significant differences were observed in in-hospital mortality., (© 2024. The Author(s).)

Background: Identifying those of patients with metastatic renal cell carcinoma (mRCC) who are most likely to benefit from cytoreductive nephrectomy (CN) is challenging. We tested the association between preoperative value of Systemic Immune-Inflammation Index (SII) and overall survival (OS) as well as cancer-specific survival (CSS) in mRCC patients treated with CN., Methods: mRCC patients treated with CN at different institutions were included. After assessing for the optimal pretreatment SII cut‑off value, we found 710 to have the maximum Youden Index value. The overall population was therefore divided into two SII groups using this cut‑off (low, <710 vs. high, ≥710). Univariable and multivariable Cox regression analyses tested the association SII and OS as well as CSS. The discrimination of the model was evaluated with the Harrel's Concordance Index (C-Index). The clinical value of the SII was evaluated with decision curve analysis (DCA)., Results: Among 613 mRCC patients, 298 (49%) patients had a SII≥710. Median follow-up was 31 (IQR 16-58) months. On univariable analysis, high preoperative serum SII was significantly associated with worse OS (HR: 1.28, 95% CI: 1.07-1.54, P=0.01) and CSS (HR: 1.29, 95% CI: 1.08-1.55, P=0.01). On multivariable analysis, which adjusted for the effect of established clinicopathologic features, SII≥710 was associated with OS (HR: 1.25, 95% CI: 1.04-1.50, P=0.02) and CSS (HR: 1.26, 95% CI: 1.05-1.52, P=0.01). The addition of SII only slightly improved the discrimination of a base model that included established clinicopathologic features (C-index: 0.637 vs. 0.629). On DCA, the inclusion of SII did not improve the net-benefit of the prognostic model. On multivariable analyses, SII≥710 remained independently associated with the worse OS and CSS in IMDC intermediate risk group (both: HR: 1.31, 95% CI: 1.02-1.67, P=0.03). In the subgroup analyses based on the BMI, among patients with BMI ≥ 25, SII was significantly associated with OS (HR: 1.29, 95% CI: 1.04-1.61, P=0.02) and CSS (HR: 1.31, 95% CI: 1.05-1.63, P=0.02)., Conclusions: We found an independent association of high SII prior to CN with unfavorable clinical outcomes, particularly in patients with intermediate risk mRCC and patients with increased BMI. Despite these results, it does not seem to add any prognostic or clinical benefit beyond that obtained by currently available clinicopathologic characteristics as sole worker.

Background: To compare the effect of robot-assisted (RAPN) vs. open (OPN) partial nephrectomy on short-term postoperative outcomes and total hospital charges in frail patients with non-metastatic renal cell carcinoma (RCC)., Methods: Within the National Inpatient Sample database we identified 2745 RCC patients treated with either RAPN or OPN between 2008 and 2015, who met the Johns Hopkins Adjusted Clinical Groups frailty-defining indicator criteria. We examined the rates of RAPN vs. OPN over time. Moreover, we compared the effect of RAPN vs. OPN on short-term postoperative outcomes and total hospital charges. Time trends and multivariable logistic, Poisson and linear regression models were applied., Results: Overall, 1109 (40.4%) frail patients were treated with RAPN. Rates of RAPN increased over time, from 16.3% to 54.7% (p < 0.001). Frail RAPN patients exhibited lower rates (all p < 0.001) of overall complications (35.3 vs. 48.3%), major complications (12.4 vs. 20.4%), blood transfusions (8.0 vs. 13.5%), non-home-based discharge (9.6 vs. 15.2%), shorter length of stay (3 vs. 4 days), but higher total hospital charges ($50,060 vs. $45,699). Moreover, RAPN independently predicted (all p < 0.001) lower risk of overall complications (OR: 0.58), major complications (OR: 0.55), blood transfusions (OR: 0.60) and non-home-based discharge (OR: 0.51), as well as shorter LOS (RR: 0.77) but also higher total hospital charges (RR: +$7682), relative to OPN., Conclusions: In frail patients, RAPN is associated with lower rates of short-term postoperative complications, blood transfusions and non-home-based discharge, as well as with shorter LOS than OPN. However, RAPN use also results in higher total hospital charges., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To determine factors associated with performing inadvertent radical nephrectomy (RN) for upper tract urothelial carcinoma (UTUC), and to assess the impact of radical nephrectomy on overall survival (OS) compared to radical nephroureterectomy (NU)., Methods: Using the National Cancer Database (NCDB), patients with UTUC of the renal pelvis who were diagnosed with renal cortical tumors and underwent RN (n = 820) with subsequent surgical pathology demonstrating urothelial carcinoma were identified. These patients were compared to those diagnosed with renal pelvis tumors who appropriately underwent NU (n = 16,464) between 2005 and 2015. Multivariable logistic regression was used to determine patient, facility and tumor-related factors associated with undergoing RN. The impact of surgery (RN vs NU) on OS was determined by Cox-regression after propensity score matching., Results: A total of 4.7% patients with UTUC underwent inadvertent RN. Black race (adjusted odds ratio [aOR] 1.62, 95%CI 1.23-2.13), larger tumors, advanced tumor stage, and high-grade tumors (P < 0.0001) were associated with RN. However, surgery at a facility performing a higher volume of NU/year was associated with lower odds of having RN performed (aOR 0.85, 95%CI 0.75-0.97). After propensity score matching, the 5-year OS was 39.9% for those undergoing RN vs 49.9% for those undergoing NU (hazard ratio 1.45, 95%CI 1.30-1.62)., Conclusion: Inadvertent RN is not uncommon, occurring in almost 5% of patients with UTUC in the NCDB. Patients who underwent RN had significantly worse OS as compared to those treated with NU. These data highlight that accurate diagnosis of UTUC is paramount and clinicians should not hesitate to perform further workup when imaging findings are equivocal., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Predictive markers can help tailor treatment to the individual in metastatic renal cell carcinoma (mRCC). De Ritis ratio (DRR) is associated with oncologic outcomes in various solid tumors., Objective: To assess the value of DRR in prognosticating survival in mRCC patients treated with tyrosine-kinase inhibitors (TKI)., Methods: Overall, 220 mRCC patients treated with TKI first-line therapy were analyzed. An optimal cut-off point for DRR was determined with Youden's J. We used multiple strata for DRR, performed descriptive, Kaplan-Meier and multivariable Cox-regression analyses to assess associations of DRR with progression-free (PFS) and overall survival (OS)., Results: Patients above the optimal cut-off point for DRR of ≥ 1.58 had fewer liver metastases (p = 0.01). There was no difference in PFS (p > 0.05) between DRR groups. DRR above the median of 1.08 (HR 1.42; p = 0.03), DRR ≥ 1.1(HR 1.44; p = 0.02), ≥ 1.8 (HR 1.56; p = 0.03), ≥ 1.9 (HR 1.59; p = 0.02) and ≥ 2.0 (HR 1.63; p = 0.047) were associated with worse OS. These associations did not remain after multivariable adjustment. In the intermediate MSKCC group, DRR was associated with inferior OS at cut-offs ≥ 1.0 (HR 1.78; p = 0.02), ≥ 1.1 (HR 1.81; p = 0.01) and above median (HR 1.88; p = 0.007) in multivariable analyses. In patients with clear-cell histology, DRR above median (HR 1.54; p = 0.029) and DRR ≥ 1.1 (HR 1.53; p = 0.029) were associated with OS in multivariable analyses., Conclusion: There was no independent association between DRR and survival of mRCC patients treated with TKI in the entire cohort. However, OS of patients with intermediate risk and clear-cell histology were affected by DRR. DRR could be used for tailored decision-making in these subgroups., (© 2021. The Author(s).)

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

Background: The NCCN guidelines recommend active surveillance (AS) as an option for the initial management of cT1a 0-2 cm renal lesions. However, data about comparison between renal cell carcinoma (RCC) 0-2 cm vs. 2.1-4 cm are scarce., Methods: Within the Surveillance, Epidemiology, and End Results database (2002-2016), 46,630 T1a N any M any stage patients treated with nephrectomy were identified. Data were tabulated according to histological subtype, tumor grade (low [LG] vs. high [HG]), as well as age category and gender. Additionally, rates of synchronous metastases were quantified., Results: Overall, 69.3 vs. 74.1% clear cell, 21.4 vs. 17.6% papillary, 6.9 vs. 6.8% chromophobe, 2.0 vs. 1.1% sarcomatoid dedifferentiation, 0.2 vs. 0.2% collecting duct histological subtype were identified for respectively 0-2 cm and 2.1-4 cm RCCs. In both groups, advanced age was associated with higher rate of HG clear cell and HG papillary histological subtype. In 0-2 cm vs. 2.1-4 cm RCCs, 13.8% vs. 20.2% individuals operated on harbored HG tumors and were more prevalent in males. Lower synchronous metastases rates were recorded in 0-2 cm RCC and ranged from 0 in respectively multilocular cystic to 0.9% in HG papillary histological subtype. The highest synchronous metastases rates were recorded in sarcomatoid dedifferentiation histological subtype (13.8% and 9.7%) in both groups., Conclusions: Relative to 2.1-4 cm RCCs, 0-2 cm RCCs harbored lower rates of HG tumors, lower rates of aggressive variant histology and lower rates of synchronous metastases. The indications and demographics of patients selected for AS may be expanded in the future to include younger and healthier patients., (Copyright © 2021. Published by Elsevier Inc.)

Objectives: To test contemporary rates and predictors of open conversion at minimally invasive partial nephrectomy (MIPN: laparoscopic or robotic partial nephrectomy)., Materials and Methods: Within the National Inpatient Sample database (2008-2015) we identified all MIPN patients and patients that underwent open conversion at MIPN. First, estimated annual percentage changes (EAPC) tested temporal trends of open conversion. Second, univariable and multivariable logistic regression models predicted open conversion at MIPN. All models were weighted and adjusted for clustering, as well as all available patient and hospital characteristics., Results: Of 7649 MIPN patients, 287 (3.8%) underwent open conversion. The rates of open conversion decreased over time (from 12 to 2.4%; EAPC: 24.8%; p = 0.004). In multivariable logistic regression models predicting open conversion, patient obesity achieved independent predictor status (OR:1.80; p < 0.001). Moreover, compared to high volume hospitals, medium volume (OR:1.48; p = 0.02) and low volume hospitals (OR:2.11; p < 0.001) were associated with higher rates of open conversion. Last but not least, when the effect of obesity was tested according to hospital volume, the rates of open conversion ranged from 2.2 (non obese patients treated at high volume hospitals) to 9.8% (obese patients treated at low volume hospitals)., Conclusion: Overall contemporary (2008-2015) rate of open conversion at MIPN was 3.8% and it was strongly associated with patient obesity and hospital surgical volume. In consequence, these two parameters should be taken into account during preoperative patients counselling, as well as in clinical and administrative decision making., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: Identifying which patients are likely to benefit from cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) is important. We tested the association between preoperative serum De Ritis ratio (DRR, Aspartate Aminotransferase/Alanine Aminotransferase) and overall survival (OS) as well as cancer-specific survival (CSS) in mRCC patients treated with CN., Material and Methods: mRCC patients treated with CN at different institutions were included. After assessing for the optimal pretreatment DRR cut-off value, we found 1.2 to have the maximum Youden index value. The overall population was therefore divided into 2 DRR groups using this cut-off (low, <1.2 vs. high, ≥1.2). Univariable and multivariable Cox regression analyses tested the association between DRR and OS as well as CSS. The discrimination of the model was evaluated with the Harrel's concordance index (C-index). The clinical value of the DRR was evaluated with decision curve analysis., Results: Among 613 mRCC patients, 239 (39%) patients had a DRR ≥1.2. Median follow-up was 31 (IQR 16-58) months. On univariable analysis, high DRR was significantly associated with OS (hazard ratios [HR]: 1.22, 95% confidence interval [CI]: 1.01-1.46, P = 0.04) and CSS (HR: 1.23, 95% CI: 1.02-1.47, P = 0.03). On multivariable analysis, which adjusted for the effect of established clinicopathologic features, high DRR remained significantly associated with both OS (HR: 1.26, 95% CI: 1.04-1.52, P = 0.02) and CSS (HR: 1.26, 95% CI: 1.05-1.53, P = 0.01). The addition of DRR only minimally improved the discrimination of a base model that included established clinicopathologic features (C-index = 0.633 vs. C-index = 0.629). On decision curve analysis, the inclusion of DRR did not improve the net-benefit beyond that obtained by established subgroup analyses stratified by IMDC risk groups, type of systemic therapy, body mass index and sarcomatoid features, did not reveal any prognostic value to DRR., Conclusion: Despite the statistically significant association between DRR and OS as well as CSS in mRCC patients treated with CN, DRR does not seem to add any further prognostic value beyond that obtained by currently available features., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: We evaluated stage at presentation and cancer specific mortality according to variant histology relative to clear cell renal cell carcinoma., Materials and Methods: Within the Surveillance, Epidemiology, and End Results registry (2001-2016) we identified variant histology and clear cell renal cell carcinoma cases. Cumulative incidence plots, multivariate Cox regression models matched for stage, grade and other patient characteristics addressed cancer specific mortality. Subgroup analyses relied on inverse probability treatment weighting according to nephrectomy type., Results: Of all 69,785 patients with renal cell carcinoma 2,495 harbored variant histology (3.6%). Of patients with variant histology 70.1% (1,748) harbored sarcomatoid vs 11.2% (280) collecting duct vs 7.6% (190) mesenchymal vs 3.8% (94) neuroendocrine vs 2.9% (72) renal medullary vs 2.5% (62) mucinous tubular and spindle cell, and 2.0% (49) rhabdoid tumors. All patients with variant histology exhibited more advanced TNM stage at diagnosis than clear cell renal cell carcinoma, except for mucinous tubular and spindle cell. After matching with G4 clear cell renal cell carcinoma, collecting duct (multivariate HR 1.6, p <0.01), sarcomatoid (HR 1.8, p <0.01), renal medullary (HR 1.7, p=0.1) and rhabdoid variant histology (HR 1.5, p=0.1) showed higher cancer specific mortality than clear cell renal cell carcinoma. No cancer specific mortality differences were recorded for mesenchymal, neuroendocrine and mucinous tubular and spindle cell variant histology. In nephrectomy subgroup higher cancer specific mortality was recorded after partial nephrectomy than radical nephrectomy in sarcomatoid variant histology after inverse probability treatment weighting and multivariate adjustment (HR 1.2, p=0.02)., Conclusions: TNM stage at diagnosis is universally more advanced in patients with variant histology, except for mucinous tubular and spindle cell. Cancer specific mortality is higher in collecting duct, sarcomatoid, rhabdoid and renal medullary variant histology, but not in other variant histology. Partial nephrectomy is associated with worse survival in sarcomatoid variant histology but could not be assessed in other variant histology due to small sample size.

Background: Tyrosine kinase inhibitor therapy (TKI) has changed the treatment paradigm of metastatic renal cell carcinoma (mRCC). The recent CARMENA and SURTIME trials challenged the role of the cytoreductive nephrectomy (CN)., Objective: To assess the impact of CN prior to TKI therapy in patients with mRCC in a real-world setting., Methods: Overall, 262 consecutive patients with mRCC were treated with CN plus TKI or TKI only at our institution between 2000 and 2016. Patients with prior immunotherapy or metastasectomy were excluded. Multiple imputation and inverse probability of treatment weighting (IPTW) were performed to account for missing values and imbalances between the treatment groups, respectively. Unadjusted and adjusted Kaplan-Meier estimates were used to determine differences in progression-free (PFS), overall (OS), and cancer-specific survival (CSS)., Results: Overall, 104 (40%) patients received CN before TKI treatment. Most frequent first line therapy was Sunitinib (66%), followed by Sorafenib (20%) and Pazopanib (10%). After adjustment with IPTW, there was no difference in PFS, CSS, and OS (all P > 0.05) between the treatment groups. In subgroup analyses, CSS was improved when CN was performed in patients with sarcomatoid features and clear cell histology (P = 0.04 and P = 0.03) and PFS was improved in patients with clear cell histology when CN was performed [0.04]). CN did not improve OS in any subgroup analysis., Conclusion: The role of CN remains controversial. We found no difference in survival outcomes between patients treated with and without CN before TKI therapy. However, CN was associated with improved survival in specific patient subgroups. Tailored, individualized treatment is key to further improve oncological outcomes for mRCC., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To test the association between metabolic syndrome (MetS) and its components (high blood pressure, body mass index [BMI]  ≥ 30, altered fasting glucose, low high-density lipoprotein cholesterol and high triglycerides) on perioperative outcomes after partial nephrectomy (PN)., Methods: Within the National Inpatient Sample database (2000-2015) we identified all PN patients. First, temporal trends of MetS were reported. Second, the effect of MetS components was tested in multivariable logistic regression models predicting overall and specific perioperative complications. Third, we tested for dose-response from the concomitant effect of multiple MetS components. All models were weighted and adjusted for clustering, as well as all available patient and hospital characteristics., Results: Of 25,875 patients: (1) 59.3% had high blood pressure, (2) 14.7% had BMI  ≥ 30, (3) 21.7% had altered fasting glucose, (4) 20.2% had high triglycerides, and (5) <0.01% had low high-density lipoprotein cholesterol. One vs 2 vs 3 vs 4 MetS components were recorded in 34.9% vs 22.9% vs 8.9% vs 2.2% patients. Of all, 11.1% exhibited  ≥ 3 components and qualified for MetS. The rates of MetS increased over time (estimated annual percentage changes: +12.0%;P <.001). The 4 tested MetS components (high blood pressure, BMI  ≥ 30, altered fasting glucose, and high triglycerides) achieved independent predictor status in multivariable models predicting overall, cardiac, miscellaneous medical, vascular, and respiratory complications, as well as transfusions. Moreover, a statistically significant dose-response was confirmed for the same endpoints., Conclusion: MetS and its components consistently and strongly predict perioperative complications after PN. Moreover, the strength of the effect was directly proportional to the number of MetS components exhibited by each individual patient, even if formal MetS diagnosis of  ≥ 3 components has not been met., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: The impact of preoperative chemotherapy in patients with upper urinary tract urothelial carcinoma remains poorly investigated. We assessed the rates of pathological complete response (pT0N0/X) and downstaging (pT1N0/X or less) at radical nephroureterectomy after preoperative chemotherapy and evaluated their impact on survival., Materials and Methods: This was an international observational study of patients who underwent preoperative chemotherapy and radical nephroureterectomy for high risk upper tract urothelial carcinoma between 2005 and 2017. Multiple imputation of chained equations was applied to account for missing values. Logistic regression analyses were performed to identify predictors of pathological response. Cox proportional hazard regression models were used to estimate recurrence-free survival, cancer specific survival and overall survival., Results: A total of 267 patients met our inclusion criteria. Among included patients 82 (31%) received methotrexate, vinblastine, doxorubicin and cisplatin; 123 (46%) gemcitabine and cisplatin; 25 (9%) gemcitabine and carboplatin; and 32 (12%) other regimens. The overall rates of pathological complete response and pathological downstaging were 10.1% and 44.9%, respectively. On multivariable analysis the use of gemcitabine and cisplatin, and gemcitabine and carboplatin was not statistically different from methotrexate, vinblastine, doxorubicin and cisplatin in achieving pathological complete response and pathological downstaging, respectively. The number of administered cycles did not appear to have an effect on pathological responses. Pathological downstaging was the strongest prognostic factor for recurrence-free survival (HR 0.2, p <0.001), cancer specific survival (HR 0.19, p <0.001) and overall survival (HR 0.40, p <0.001)., Conclusions: Pathological downstaging after preoperative chemotherapy is a robust prognostic factor at radical nephroureterectomy and is associated with improved survival outcomes. Although preoperative chemotherapy appears to be effective, well designed prospective studies are still needed.

Background: Local tumor ablation (LTA) and non-interventional management (NIM) emerged as alternative management options for T1a renal cell carcinoma (RCC). We investigated trends and cancer-specific mortality (CSM) after LTA and NIM, compared to partial nephrectomy (PN)., Methods: Within the Surveillance, Epidemiology, and End Results database (2004-2015), T1a RCC patients treated with PN, LTA or NIM were identified. Estimated annual proportion change methodology (EAPC), 1:1 ratio propensity score (PS) matching, cumulative incidence plots and multivariable competing risks regression models (CRR) were used to compare LTA vs. PN and NIM vs. PN. Subgroup analyses focused on patients <65 and ≥65 years., Results: Overall 4524 patients underwent LTA vs. 1654 NIM vs. 25,435 PN. Annuals rates increased for NIM (EAPC: +3.3%, P<0.001), but not for either LTA or PN. After PS-matching in multivariable CCR, LTA (HR 1.9, P<0.001) and NIM (HR 3.0, P<0.001) showed worse 5-year CSM, relative to PN. In subgroup analyses, LTA showed no CSM disadvantage relative to PN in younger patients (HR 2.0, P=0.07). In older patients 1.64-fold CSM increase was recorded. Conversely, NIM younger (HR 3.1, P=0.001) and older (HR 3.1, P<0.001) patients exhibited higher CSM relative to PN., Conclusions: In T1a RCC patients, NIM rates showed a modest but significant increase, while LTA and PN rates remained stable. In survival analyses, LTA exhibited higher CSM rates only for elderly patients. Conversely, NIM exhibited higher CSM rates in both younger and older patients.

Background: Lymph node invasion (LNI) at nephrectomy is one of the most important predictors of mortality in patients with nonmetastatic renal cell carcinoma (RCC). We analyzed the effect of histology on lymph node metastases at nephrectomy and its effect on survival in a contemporary cohort of patients with nonmetastatic RCC., Methods: Within the Surveillance, Epidemiology, and End Results database (2004-2015), we identified 100,060 patients with clear-cell, papillary, chromophobe, sarcomatoid, and collecting duct RCC, who underwent nephrectomy with or without lymph node dissection for nonmetastatic RCC. Logistic regression models, cumulative incidence plots, and competing-risks regression models were performed., Results: Overall, 10,590 patients underwent lymph node dissection for nonmetastatic RCC. Of these, LNI was recorded in 52 (7.0%), 615 (8.7%), 282 (13.9%), 316 (25.1%), 129 (38.3%), 45 (71.4%) patients with chromophobe, clear-cell, nonotherwise specified RCC, papillary, sarcomatoid, and collecting duct RCC histological subtypes, respectively. In logistic regression models, relative to clear-cell, papillary Odds ratio (OR 3.9), sarcomatoid (OR 6.3), collecting duct (OR 14.6) but not chromophobe RCC (OR 0.9; P = 0.5) independently predicted LNI at surgery. Moreover, in competing-risks regression models, LNI increased the risk of CSM 1.8-fold for sarcomatoid, 3.6-fold for clear-cell, 4.1-fold for papillary, and 6.7-fold for chromophobe histological subtype., Conclusions: Histology is an independent predictor of increased risk of LNI at nephrectomy. Moreover, the effect of pathological nodal stage on survival differs according to different histology., Competing Interests: Conflict of interest All authors declare no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Conditional survival (CS) may reveal important differences in cancer-specific mortality (CSM) among patients with nonmetastatic renal cell carcinoma (nmRCC). This study assessed CS according to T and N stages in patients treated surgically for nmRCC., Patients and Methods: Within the SEER database (2001-2015), all patients with nmRCC treated with either partial or radical nephrectomy were identified. CSM-free estimates according to T and N stage and substage groupings (pT1aN0-pT4N0 and pTanyN1) and multivariable Cox regression models with adjustment for Fuhrman grade and histologic subtype were assessed., Results: According to T and N stage and substage groupings, the following patients were included in the study: 35,966 (46.2%) with pT1aN0 disease; 18,858 (24.2%) with pT1bN0; 5,977 (7.7%) with pT2aN0; 2,511 (3.2%) with pT2bN0; 11,839 (15.2%) with pT3aN0; 1,037 (1.3%) with pT3b-cN0; 402 (0.5%) with pT4N0; and 1,302 (1.7%) with pTanyN1. Conditional CSM-free survival estimates were 98.2% at 1 year versus 98.0% at 10 years of event-free follow-up for patients with pT1aN0 disease, relative to baseline. Conversely, pT4N0/pTanyN1 conditional CSM-free survival estimates were 55.8% at 1 year versus 77.9% at 8 years of event-free follow-up. Attrition due to mortality was highest in patients with pT4N0/pTanyN1 disease. In multivariable Cox regression analyses, T stage, tumor grade, and histologic subtype represented independent predictors, but no interactions were identified., Conclusions: Tumor stage and its substages represent extremely important determinants of prognosis after lengthy event-free follow-up. The recorded observations have critical importance for physicians regarding patient follow-up and counseling.

Purpose: Cryoablation is done in select patients with pT1b nonmetastatic renal cell carcinoma without convincing proof of efficacy. Our aim was to test for differences in the cancer specific mortality rate for cryoablation and partial nephrectomy in T1b nonmetastatic renal cell carcinoma cases., Materials and Methods: In the 2004 to 2015 SEER (Surveillance, Epidemiology, and End Results) database we identified 5,763 patients with a T1b tumor treated with cryoablation or partial nephrectomy. Modeling relied on multivariable logistic regression models predicting cryoablation vs partial nephrectomy. After 1:2 ratio propensity score matching between patients treated with cryoablation vs partial nephrectomy we used cumulative incidence plot and competing risks regression to test differences in cancer specific mortality and other cause mortality rates., Results: Relative to the 5,521 patients who underwent partial nephrectomy the 242 treated with cryoablation were older, had smaller tumors and more frequently harbored unclassified renal cell carcinoma of low or unknown grade. Median followup was 38 months. In multivariable logistic regression models predicting cryoablation vs partial nephrectomy more advanced patient age was an independent predictor (OR 1.03; p=0.007). After propensity score matching and other cause mortality adjustment the 5-year cancer specific mortality rate was 2.5-fold higher after cryoablation than after partial nephrectomy (p=0.03). Conversely after propensity score matching and cancer specific mortality adjustment the 5-year other cause mortality rate was similar to that of partial nephrectomy after cryoablation (HR 1.45, p=0.12). The major limitation of this study was the lack of recurrence and metastatic progression data., Conclusions: The current findings demonstrated a 2.5-fold increase in cancer specific mortality when cryoablation was performed in patients with pT1b renal cell carcinoma. This observation should be interpreted as a contraindication to cryoablation outside clinical trials or institutional protocols.

Objectives: Our aim was to determine whether using an organ transplant-based(TB) approach reduces postoperative complications(PCs) following radical nephrectomy(RN) and tumor thrombectomy(TT) in renal cell carcinoma(RCC) patients with level II-IV thrombi., Methods: A total of 390(292 non-TB/98 TB) IRCC-VT Consortium patients who received no preoperative embolization/IVC filter were included. Stepwise linear/logistic regression analyses were performed to determine significant multivariable predictors of intraoperative estimated blood loss(IEBL), number blood transfusions received, and overall/major PC development within 30days following surgery. Propensity to receive the TB approach was controlled., Results: The TB approach was clearly superior in limiting IEBL, blood transfusions, and PC development, even after controlling for other significant prognosticators/propensity score(P < .000001 in each case). Median IEBL for non-TB/TB approaches was 1000 cc/300 cc and 1500 cc/500 cc for tumor thrombus Level II-III patients, respectively, with no notable differences for Level IV patients(2000 cc each). In comparing PC outcomes between non-TB/TB patients with a non-Right-Atrium Cranial Limit, the observed percentage developing a: i) PC was 65.8%(133/202) vs. 4.3%(3/69) for ECOG Performance Status(ECOG-PS) 0-1, and 84.8%(28/33) vs. 25.0%(4/16) for ECOG-PS 2-4, and ii) major PC was 16.8%(34/202) vs. 1.4%(1/69) for ECOG-PS 0-1, and 27.3%(9/33) vs. 12.5%(2/16) for ECOG-PS 2-4. Major study limitation was the fact that all TB patients were treated by a single, experienced, high volume surgeon from one center (non-TB patients were treated by various surgeons at 13 other centers)., Conclusions: Despite this major study limitation, the observed dramatic differences in PC outcomes suggest that the TB approach offers a major breakthrough in limiting operative morbidity in RCC patients receiving RN and TT., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Historically, partial nephrectomy (PN) showed no benefit on other-cause mortality (OCM) in elderly patients with small renal masses., Objective: To test the effect of PN versus radical nephrectomy (RN) on OCM, cancer-specific mortality (CSM), as well as 30-d mortality in patients with nonmetastatic T1a renal cell carcinoma (RCC), aged ≥75 yr old., Design, Setting, and Participants: Within the Surveillance, Epidemiology and End Results registry (2004-2014), we identified surgically treated patients with nonmetastatic pT1a RCC aged ≥75 yr., Outcome Measurements and Statistical Analysis: We relied on propensity score (PS) matching to reduce the effect of inherent differences between PN and RN. After PS matching, cumulative incidence, multivariable competing-risks regression (CRR) and logistic regression models were used. LOESS plots graphically depicted the relation between nephrectomy type and OCM after adjustment for all the covariates. Landmark analyses at 6 mo tested for immortal time bias., Results and Limitations: Of all 4541 patients, 41.6% underwent PN. After 1:1 PS matching, 2826 patients remained. In multivariable CRR models, lower OCM rates were recorded in PN patients (hazard ratio [HR]: 0.67, confidence interval [CI]: 0.54-0.84; p<0.001). LOESS plots showed lower OCM rates after PN across all examined ages. Lower CSM rates were also recorded in PN patients (HR: 0.64, CI=0.44-0.92; p=0.02). Landmark analyses rejected the hypothesis of immortal time bias. Finally, PN did not result in different 30-d mortality rates (odds ratio: 1.87; CI: 0.79-4.47; p=0.2) versus RN. Data are retrospective., Conclusions: PN results in lower OCM in elderly patients with pT1a RCC. Moreover, PN does not contribute to higher CSM or 30-d mortality in patients aged ≥75 yr. In consequence, PN should be given strong consideration, even in elderly patients., Patient Summary: Partial nephrectomy (PN) may protect from renal insufficiency, hypertension, and other unfavorable health outcomes, even in elderly patients. This protective effect results in lower other-cause mortality. Moreover, PN benefits are not undermined by higher cancer-specific mortality or 30-d mortality., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: The benefit of cytoreductive nephrectomy (CNT) for cancer-specific mortality (CSM)-free survival is unclear in contemporary metastatic non-clear cell renal cell carcinoma (non-ccmRCC) patients., Objective: To assess the role of CNT in non-ccmRCC patients., Design, Setting, and Participants: Within Surveillance, Epidemiology, and End Results registry (2001-2014), we identified patients with non-ccmRCC., Intervention: CNT versus no CNT in non-ccmRCC patients., Outcome Measurements and Statistical Analysis: Multivariable logistic regression, cumulative incidence, competing-risks regression models, incremental survival benefit (ISB), conditional survival, and landmark analyses were performed. Sensitivity analyses focused on histological subtypes and most contemporary patients (2010-2014)., Results and Limitations: Of 851 patients with non-ccmRCC, 67.6% underwent CNT. In multivariable logistic regression, year of diagnosis in contemporary (p<0.001) and intermediate (p=0.008) tertiles, as well as age ≥75 yr (p<0.001) yielded lower CNT rates. Cumulative incidence showed 2-yr CSM of 52.6% versus 77.7%, respectively, after CNT versus no CNT. CSM after CNT versus no CNT was invariably lower in all histologic subtypes and in contemporary patients. Multivariable competing-risks regression models predicting CSM favored CNT (hazard ratio [HR]: 0.38, confidence interval: 0.30-0.47, p<0.001) in all patients and in all subgroups defined by histologic subtypes (HR: 0.14-0.43, all p≤0.02), as well as in contemporary patients (HR: 0.32, p<0.001). The ISB analyses yielded statistically significant and clinically meaningful CSM-free survival benefit of +3 mo after CNT versus no CNT in individuals with observed CSM-free survival ≤24 mo. The 2-yr CSM-free survival increased from baseline of 46.1% versus 19.4% (Δ=26.7%, p<0.001) to 70.3% versus 54.4% (Δ=15.9%, p=0.005) after CNT versus no CNT, in patients that survived 12 mo, respectively. Landmark analyses rejected bias favoring CNT. Data were retrospective., Conclusions: CSM is lower after CNT for non-ccmRCC in all histologic subtypes and in contemporary patients except for unproven ISB in collecting duct patients. This observation should encourage greater CNT consideration in non-ccmRCC., Patient Summary: Cytoreductive nephrectomy appears to improve survival in metastatic non-clear cell renal cell carcinoma, but it is used infrequently., (Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Aim: To investigate the association of perioperative blood transfusion (PBT) with oncologic outcomes in patients with renal cell carcinoma (RCC), we conducted a systematic review and meta-analysis of the literature to clarify the long-term oncologic effect of PBT in patients undergoing nephrectomy for RCC., Materials and Methods: We searched the MEDLINE, Web of Science, Cochrane Library and Scopus on 15th April 2018 to identify studies that compared patients who received PBT undergoing radical or partial nephrectomy for RCC to patients who did not with the aim of evaluating its impact on overall mortality (OM), cancer-specific mortality (CSM) and disease recurrence using multivariable cox regression analysis., Results: A total of 19,681 patients in 7 studies matched the selection criteria for the systematic review and meta-analysis. All 7 studies were retrospective design and published between 1994 and 2018. Our study included low quality of eligible studies due to their retrospective design and showed a significant heterogeneity. PBT was associated with OM (pooled hazard ratio [HR], 1.49, 1.24-1.78), CSM (pooled HR, 1.46, 1.20-1.77), and disease recurrence (pooled HR, 1.80, 1.03-3.12). In a subgroup analysis of 3,664 patients with nonmetastatic RCC, PBT was remained associated with OM (pooled HR, 1.91; 1.06-3.41), but not anymore with CSM (pooled HR, 1.92, 0.94-3.91) or disease recurrence (pooled HR, 2.18, 0.86-5.55)., Conclusions: PBT in patients undergoing nephrectomy for RCC is associated with worse overall survival. While PBT may be reflective of the underlying aggressiveness of the disease, it could be that its detrimental effect on outcomes is caused by its negative effect on the host's resilience., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Partial nephrectomy (PN) is technically feasible in patients with metastatic renal cell carcinoma (mRCC). We tested the contemporary effect of PN on cancer-specific mortality (CSM), other-cause mortality (OCM) and early postoperative outcomes compared to radical nephrectomy (RN) in mRCC patients., Materials and Methods: In the first part, we identified surgically treated mRCC patients within the SEER database (2004-2013). After propensity-score (PS) matching, cumulative incidence plots and multivariable competing-risks regression (CRR) models were used. In the second part, we identified surgically treated mRCC patients within the NIS database (2004-2013). After PS matching, multivariable logistic regression (MLR) and multivariable Poisson regression (MPR) models were used., Results: Within the SEER database, 217 (4.2%) of 5171 mRCC patients underwent PN. After 4:1 PS matching, multivariable CRR models showed lower OCM rates in PN patients (hazard ratio [HR]: 0.23, p = 0.01). No difference in CSM was reported in PN vs. RN patients (p = 0.08). Within the NIS database, 226 (4.4%) of 5138 patients underwent PN. After 4:1 PS matching, MLR showed lower rates of transfusions (odds ratio [OR]: 0.46, P < 0.001), intraoperative (OR: 0.33, p = 0.02) and miscellaneous surgical complications (OR: 0.42, p = 0.009) in PN vs. RN patients. No difference in overall complications (OR: 1.00, p = 0.9) and in-hospital mortality (OR: 1.2, p = 0.8) was observed. In MPR, PN did not affect LOS (OR: 0.94, p = 0.3)., Conclusions: We demonstrate that PN is associated with lower OCM in the setting of mRCC, but not with differences in other examined endpoints. In consequence, PN merits greater consideration in the context of mRCC., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: A few studies addressed predictive factors of cancer-specific mortality (CSM) in patients with recurrent renal cell carcinoma (RCC) following surgery. Time to recurrence (TTR) is an important predictor of CSM in various types of cancers. The aim of our study was to describe the course of RCC following disease recurrence and to identify prognostic factors that influence CSM with a special focus on TTR., Materials and Methods: Retrospective analysis of 331 patients who experienced disease recurrence after radical nephrectomy (n = 307) or partial nephrectomy (n = 24) with curative intent. A Cox proportional hazards regression model addressed the association between various clinicopathologic features and CSM after disease recurrence. TTR was defined as time from surgery to occurrence of disease recurrence., Results: Of the 331 patients, 232 (70%) were male, and 99 (30%) were female. The median age at surgery was 62 years (interquartile range, 53-69 years). Median time from nephrectomy to disease recurrence was 1.2 years (interquartile range, 0.5-3.3 years). Of the recurrences, 63 (19%) were local, and 268 (81%) were distant. Shorter time to recurrence (P = .0008), female gender (P = .035), and distant versus local recurrence location (P < .0001) were found to be independently associated with CSM following disease recurrence., Conclusions: In patients experiencing disease recurrence after nephrectomy for presumably localized RCC, shorter TTR, female gender, and distant recurrence were found to be associated with worse CSM. The inclusion of these factors into risk-stratification tools may help patient counseling and decision-making regarding type and regimen of salvage treatment., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: To test rates over time of robotic partial and radical nephrectomy (RPN and RRN) at teaching vs nonteaching institutions and to examine associated complication rates and length of stay., Materials and Methods: Within the National Inpatient Sample (2008-2013), after stratification according to institutional teaching status, we examined the rates of robotic, open, and laparoscopic PN and RN. Subsequently, we tested complication rates and length of stay associated with RPN or RRN according to institutional teaching status. We relied on estimated annual percentage change (EAPC) with the least squares linear regression to test temporal trends and on multivariable logistic regression (MLR) and Poisson regression models to test complication rates and length of stay., Results: Overall, 4070 and 1683 RPN and RRN were identified. In MLR, RPN rates were lower at teaching vs nonteaching institutions (odds ratio [OR]: 0.79, p < 0.001). RPN increased at similar rates over time at teaching and nonteaching institutions (EAPC: +32.1% and +30.1%, all p < 0.05). In MLR, RRN rates were similar at teaching and nonteaching institutions (p: 0.4). RRN rate increase over time was of similar magnitude at teaching vs nonteaching institutions (EAPC: +35.5% and +43.0%, all p < 0.05). RPN at teaching institutions yielded higher genitourinary complication rates (OR: 1.46, p: 0.01). RRN at teaching institutions resulted in lower respiratory complications (OR: 0.66, p: 0.04) and shorter length of stay (rate ratio [RR]: 0.93, p: 0.01), but higher intraoperative complication rates (OR: 3.39, p: 0.04)., Conclusion: Despite statistically significant differences in rates of RPN use, according to the institutional teaching status and despite statistically significant difference in selected complications, no meaningful differences distinguish teaching vs nonteaching institution when RPN and RRN are considered.

Aim: To test the effect of African-American race on cancer specific mortality (CSM) in clear cell metastatic renal cell carcinoma (ccmRCC) and non-ccmRCC., Patients and Methods: Within Surveillance, Epidemiology and End Results registry (2001-2014), we identified patients with ccmRCC and non-ccmRCC. We relied on propensity score (PS) matching to reduce the effect of inherent differences between African-American vs. Caucasian patients. After PS matching that included access to cytoreductive nephrectomy (CNT), cumulative incidence, competing-risks regression (CRR) models and landmark analyses tested the effect of race on CSM., Results: Before PS matching, African-American patients accounted for 7.0 and 24.5% of respectively ccmRCC (N = 6742) and non-ccmRCC patients (N = 766). After PS matching, African-American patients accounted for 22.3 and 33.5% of respectively ccmRCC (N = 2050) and non-ccmRCC (N = 391) matched cohorts. In multivariable CRR models focusing on ccmRCC, higher CSM was recorded in African-Americans (HR:1.27, p < 0.001). Conversely, in non-ccmRCC, lower CSM was recorded in African-Americans (HR:0.54, p < 0.001). Landmark analyses rejected the hypothesis of immortal time bias., Conclusion: African-Americans experienced higher CSM in ccmRCC. Conversely, African-Americans experienced lower CSM, when diagnosed with non-ccmRCC. These differences are independent of access to CNT and warrant further study since they may have an impact on efficacy or access to systemic therapies., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose of Review: Various ischemia type during partial nephrectomy for renal cell cancer (RCC) resulted in different postoperative functional outcomes. Our objective was to systematically review the contemporary literature on robot-assisted partial nephrectomy (RPN) and investigate the association of ischemia type and tumor complexity with postoperative functional outcomes of the operated kidney and overall., Recent Findings: Forty-five of the 99 reports identified were selected for qualitative analysis. All included studies were observational and nonrandomized. Overall, we found that patients undergoing RPN with zero ischemia and selective artery clamping had a lower decrease in glomerular filtration rates of the operated kidney in comparison to both warm and cold ischemia. This association seems also to play a role in patients with bilateral kidneys harboring complex tumors., Summary: Zero ischemia and selective artery clamping provide the best functional outcomes following robotic partial nephrectomy. This seems to be of particular relevance in patients with single kidney or tumors of high complexity. Whether these changes are statistically or clinically significant cannot be determined within this systematic review.

Purpose of Review: To evaluate current literature reporting oncologic outcomes after robot-assisted partial nephrectomy (RAPN) and laparoscopic partial nephrectomy (LPN)., Recent Findings: Recently, there have been published first mid-term results after RAPN (5 years). To date, there are no randomized trials to guide decision-making regarding LPN or robotic partial nephrectomy (RPN), and such trials are unlikely to be forthcoming, given the rapid adoption of RAPN worldwide. We performed a literature search according to Cochrane guidelines up to 1 September 2017, including studies that had more than 40 months of oncologic follow-up., Summary: A total of 2933 patients were included from 14 studies (1498 RAPN, 1525 LPN). RAPN had similar mid-term (5 years) oncologic outcomes as LPN. Large collaborative efforts are still necessary to provide solid long-term oncologic outcomes of open, laparoscopic, and RPN.

Objectives: To study the effect of lymph node dissection (LND) at the time of nephrectomy and tumor thrombectomy on oncological outcomes in patients with renal cell carcinoma (RCC) and tumor thrombus., Patients and Methods: The records of 1,978 patients with RCC and tumor thrombus who underwent radical nephrectomy and tumor thrombectomy from 1985 to 2014 at 24 centers were analyzed. None of the patients had distant metastases. Extent and pathologic results of LND were compared with respect to cancer-specific survival (CSS). Multivariable Cox regression models were used to quantify the effect of multiple covariates., Results: LND was performed in 1,026 patients. In multivariable analysis, the presence of LN metastasis, the number of positive LNs, and LN density were independently associated with cancer-specific mortality (CSM). Clinical node-negative (cN-) disease was documented in 573 patients, 447 of them underwent LND with 43 cN- patients (9.6%) revealing positive LNs at pathology. LN positive cN- patients showed significantly better CSS when compared to LN positive cN+ patients. In multivariable analysis, positive cN status in LN positive patients was a significant predictor of CSM (HR, 2.923; P = 0.015)., Conclusions: The number of positive nodes harvested during LND and LN density was strong prognostic indicators of CSS, while number of removed LNs did not have a significant effect on CSS. The rate of pN1 patients among clinically node-negative patients was relatively high, and LND in these patients suggested a survival benefit. However, only a randomized trial can determine the absolute benefit of LND in this setting., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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.)

Purpose: Because the prognostic impact of the clinical and pathological features on cancer-specific survival (CSS) and overall survival (OS) in patients with papillary renal cell carcinoma (papRCC) is still controversial, we want to assess the impact of clinicopathological features, including Fuhrman grade and age, on survival in surgically treated papRCC patients in a large multi-institutional series., Methods: We established a comprehensive multi-institutional database of surgically treated papRCC patients. Histopathological data collected from 2189 patients with papRCC after radical nephrectomy or nephron-sparing surgery were pooled from 18 centres in Europe and North America. OS and CSS probabilities were estimated using the Kaplan-Meier method. Multivariable competing risks analyses were used to assess the impact of Fuhrman grade (FG1-FG4) and age groups (<50 years, 50-75 years, >75 years) on cancer-specific mortality (CSM)., Results: CSS and OS rates for patients were 89 and 81% at 3 years, 86 and 75% at 5 years and 78 and 41% at 10 years after surgery, respectively. CSM differed significantly between FG 3 (hazard ratio [HR] 4.22, 95% confidence interval [CI] 2.17-8.22; p < 0.001) and FG 4 (HR 8.93, 95% CI 4.25-18.79; p < 0.001) in comparison to FG 1. CSM was significantly worse in patients aged >75 (HR 2.85, 95% CI 2.06-3.95; p < 0.001) compared to <50 years., Conclusions: FG is a strong prognostic factor for CSS in papRCC patients. In addition, patients older than 75 have worse CSM than patients younger than 50 years. These findings should be considered for clinical decision making.

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.)

Aim of this study was to analyse the association between the use of diagnostic ureteroscopy (URS) and the development of intravesical recurrence (IVR) in patients undergoing radical nephroureterectomy (RNU) for high-risk upper tract urothelial carcinoma. A systematic review of the published data was performed up to December 2016, using multiple search engines to identify eligible studies. A formal meta-analysis was conducted of studies comparing patients who underwent URS before RNU with those who did not. Hazard ratios (HRs), with their 95% confidence intervals (CIs), from each study were used to calculate pooled HRs. Pooled estimates were calculated using a fixed-effects or random-effects model according to heterogeneity. Statistical analyses were performed using RevMan, version 5. Seven studies were included in the systematic review, but only six of these were deemed fully eligible for meta-analysis. Among the 2 382 patients included in the meta-analysis, 765 underwent diagnostic URS prior to RNU. All examined studies were retrospective, and the majority examined Asian populations. The IVR rate ranged from 39.2% to 60.7% and from 16.7% to 46% in patients with and without prior URS, respectively. In the pooled analysis, a statistically significant association was found between performance of URS prior to RNU and IVR (HR 1.56, 95% CI 1.33-1.88; P < 0.001). There was no heterogeneity in the observed outcomes, according to the I 2 statistic of 2% (P = 0.40). Within the intrinsic limitations of this type of analysis, these findings suggest a significant association between the use of diagnostic URS and higher risk of developing IVR after RNU. Further research in this area should be encouraged to further investigate the possible causality behind this association and it potential clinical implications., (© 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.)

Purpose: To review the contemporary data on the role of lymph node dissection (LND) at the time of radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC)., Methods: A computerized bibliographic search using the following protocol ("Nephroureterectomy") AND ("Lymphadenectomy" OR "Lymph node" OR "Lymphatic") was performed in MEDLINE to identify all original and review articles that addressed the role of LND for UTUC., Results: Regional lymph node (LN) boundaries of UTUC have been recently investigated in mapping studies to propose anatomic templates of LND according to the laterality and location of primary tumor. Although these anatomic templates remained poorly described, most reports supported the staging benefit of LND that allowed for risk stratification of patients with (pN+) or without (pN0) LN metastases from those who did not undergo such a procedure (pNx). In addition, the therapeutic benefit of LND at the time of RNU was supported by better oncological outcomes obtained after complete LND when compared to incomplete or no LND, especially in the group of patients with advanced disease. The number of LNs removed was also correlated with both, more accurate staging and greater cancer-specific survival after LND, whose feasibility and safety have been validated in prospective studies., Conclusions: Despite mostly based on data with level of evidence 3, our comprehensive review of the literature supports the staging and therapeutic benefits of LND at the time of RNU for UTUC, which are particularly significant for patients with muscle-invasive or locally advanced disease.

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: Several retrospective studies with small cohorts reported neutrophil-to-lymphocyte ratio (NLR) as a prognostic marker in upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy (RNU). We aimed at validating the predictive and prognostic role of NLR in a large multi-institutional cohort., Methods: Preoperative NLR was assessed in a multi-institutional cohort of 2477 patients with UTUC treated with RNU. Altered NLR was defined by a ratio >2.7. Logistic regression analyses were performed to assess the association between NLR and lymph node metastasis, muscle-invasive and non-organ-confined disease. The association of altered NLR with recurrence-free survival (RFS) and cancer-specific survival (CSS) was evaluated using Cox proportional hazards regression models., Results: Altered NLR was observed in 1428 (62.8 %) patients and associated with more advanced pathological tumor stage, lymph node metastasis, lymphovascular invasion, tumor necrosis and sessile tumor architecture. In a preoperative model that included age, gender, tumor location and architecture, NLR was an independent predictive factor for the presence of lymph node metastasis, muscle-invasive and non-organ-confined disease (p < 0.001). Within a median follow-up of 40 months (IQR 20-76 months), 548 (24.1 %) patients experienced disease recurrence and 453 patients (19.9 %) died from their cancer. Compared to patients with normal NLR, those with altered NLR had worse RFS (0.003) and CSS (p = 0.002). In multivariable analyses that adjusted for the effects of standard clinicopathologic features, altered NLR did not retain an independent value. In the subgroup of patients treated with lymphadenectomy in addition to RNU, NLR was independently associated with CSS (p = 0.03)., Conclusion: In UTUC, preoperative NLR is associated with adverse clinicopathologic features and independently predicts features of biologically and clinically aggressive UTUC such as lymph node metastasis, muscle-invasive or non-organ-confined status. NLR may help better risk stratify patients with regard to lymphadenectomy and conservative therapy., Competing Interests: The authors declare that they have no conflict of interest. Ethical standards This study has been approved by the appropriate ethics committee.

Objectives: To examine, using competing risks regression, differences in cancer-specific mortality (CSM) that might distinguish between local tumour ablation (LTA) and observation (OBS) for patients with kidney cancer., Patients and Methods: The study focused on 1 860 patients with cT1a kidney cancer treated with either LTA or OBS between 2000 and 2009 in the Surveillance Epidemiology and End Results-Medicare database. Propensity-score matching was used. The study outcome was CSM. Multivariable competing risks regression analyses, adjusting for other-cause mortality as well as patient (including comorbidities) and tumour characteristics, were fitted., Results: Overall, fewer patients underwent LTA than OBS (30 vs 70%; n = 553 vs n = 1 307). Compared with patients in the OBS group, those in the LTA group were younger (median age 77 vs 78 years; P < 0.001), more likely to be white (84 vs 78%; P = 0.005), more frequently married (59 vs 52%; P = 0.02) and more frequently of high socio-economic status (54 vs 45%; P = 0.001). After propensity-score matching, 553 patients who underwent LTA and 553 who underwent OBS remained for subsequent analyses. The mean standardized differences of patient characteristics between the two groups were <10%, indicating a high degree of similarity. After LTA or OBS, the 5-year CSM estimates from Poisson regression-derived smoothed plots were 3.5 and 9.1%, respectively. In multivariable competing risks regression analyses, LTA use was found to have a protective effect on CSM (hazard ratio 0.47 [95% confidence interval 0.25-0.89]; P = 0.02)., Conclusions: After adjustment for comorbidity and tumour characteristics in elderly patients with kidney cancer, LTA was associated with a clinically and statistically significant protective effect on CSM, compared with OBS. This advantage of LTA deserves consideration when obtaining informed consent., (© 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.)

Background: Sarcomatoid renal cell carcinoma (sRCC) is a rare histological subtype that is associated with unfavorable prognosis. We sought to examine the effect of sRCC on cancer-specific mortality (CSM) relative to clear cell renal cell carcinoma (ccRCC), after adjusting for other variables, as well as other-cause mortality (OCM)., Methods: We relied on the Surveillance, Epidemiology, and End Results-Medicare database from 2000 to 2009 to identify a cohort of 7916 patients with either sRCC (n = 234) or ccRCC (n = 7682) who received surgery as primary treatment. Patient, tumor, and treatment characteristics were evaluated. Then, 5-year smoothed Poisson regression CSM and OCM estimates were generated for stage-by-stage comparisons between sRCC and ccRCC. A multivariable competing-risks regression model predicting CSM and adjusting for several patient and tumor characteristics, as well as OCM, was finally fitted., Results: Compared to ccRCC patients, sRCC patients had more advanced and more aggressive disease at diagnosis. Specifically, 48 and 7 % of sRCC and ccRCC patients presented with stage IV disease, respectively (p < 0.001). Overall, 5-year CSM and OCM estimates were 67 and 17 % for sRCC patients and 14 and 19 % for ccRCC patients. In stage-by-stage analyses, sRCC was invariably associated with worse CSM. After adjusting for several characteristics as well as OCM, sRCC was associated with a 3.2 higher risk of CSM compared with ccRCC., Conclusions: Patients with sRCC are present with more advanced disease. Moreover, sRCC is associated with a higher rate of CSM, even after adjusting for several characteristics and OCM.

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.)

Objective: To evaluate potential differences in local tumor ablation (LTA) perioperative outcomes between the percutaneous LTA (pLTA) and the laparoscopic LTA (lapLTA) approaches., Methods: Using the Surveillance, Epidemiology, and End Results-Medicare, we identified all patients diagnosed with T1a renal cell carcinoma (RCC) who underwent either pLTA or lapLTA between 2000 and 2009. Overall complications at 30 days and mortality at 90 days were examined for both groups. A multivariable logistic regression model was fitted to evaluate the effect of the approach on perioperative complications. A second model was fitted to test for associations between patient or tumor characteristics and type of LTA approach., Results: Overall, 516 patients diagnosed with T1a RCC were identified. Of those, 289 (56%) were treated with pLTA and 227 (44%) were treated with lapLTA. LapLTA-treated patients were younger (median 76 vs 78, P < .001) and healthier (median Charlson comorbidity index 2.1 vs 2.7, P = .03) than their counterpart. After pLTA and lapLTA, overall complication rates were 21% and 25%, respectively (P = .3). Similarly, 90-day mortality rates did not differ between the two groups (P = 1). After adjusting for patient and tumor characteristics, LTA approach was not associated with perioperative complications (odds ratio: 1.38, P = .1). However, older and sicker patients were less likely to be treated with lapLTA (both ≤ 0.04)., Conclusion: No differences in 30-day overall complications or 90-day mortality rates were detected between lapLTA and pLTA for T1a RCC. pLTA was more frequently used in older and sicker individuals. Further prospective studies comparing both procedures should be undertaken., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To describe renal functional outcomes after partial nephrectomy (PN) for a tumor in a solitary kidney using the estimated glomerular filtration rate eGFR (MDRD equation)., Patients and Methods: A retrospective review of 103 cases of PN in a solitary kidney at Memorial Sloan-Kettering Cancer Center from December 1989 to July 2010 was conducted. The postoperative eGFR measurements were broken into three timeframes: 1-10 days after PN, 10 days-8 weeks after PN, and 4-12 months after PN. Several factors were analyzed for their impact on postoperative eGFR on univariate and multivariable analyses. To illustrate the change in eGFR after surgery over time, a univariate generalized estimating equation (GEE) model was constructed., Results: Median preoperative eGFR was 47 ml/min/1.72 m(2) (IQR 39, 58). Higher preoperative eGFR, younger age at the time of PN, less estimated blood loss during PN, increased time between PN and previous radical nephrectomy, and decreased arterial clamp (ischemia) time were all significantly associated with increased postoperative eGFR in the early postoperative period on multivariable analysis. Younger age and higher preoperative eGFR were the only variables significantly associated with increased postoperative eGFR at all three time points. From the GEE model, postoperative eGFR continues to rise after PN until it reaches a plateau approximately 1 month after PN without attaining preoperative levels., Conclusion: PN for tumors in a solitary kidney is feasible and safe. In our model, non-modifiable factors predict the long-term postoperative eGFR: Young patients with healthy kidneys have superior renal functional results.

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: We created a prognostic tool for the prediction of oncologic outcomes after radical nephroureterectomy (RNU) for high-grade non-metastatic upper tract urothelial carcinoma (UTUC)., Methods: UTUC collaboration was utilized to include 586 patients who underwent RNU for non-metastatic high-grade UTUC. Survival outcomes were compared according to a score defined based on the sum of the independent prognostic variables., Results: The study included 382 males with a median age 70 years (range 28-97). Independent prognostic factors included: T (t stage), A (architecture), LVI (lympho-vascular invasion) and L (lymphadenectomy). TALL score (1-7) was the sum of T (≤T1 = 1, T2 = 2, T3 = 3 and T4 = 4), A (papillary = 0 and sessile = 1), LVI (absent = 0 and present = 1) and L (lymphadenectomy = 0 and no lymphadenectomy = 1). Five-year disease-free survival (DFS) and cancer-specific survival (CSS) were stratified into four risk categories according to the TALL score: low (TALL 0-2; 86 % DFS and 90 % CSS), intermediate (TALL = 3; 71 % DFS and 75 % CSS), high (TALL = 4; 57 % DFS and 58 % CSS) and very high risk (TALL ≥ 5; 34 % DFS and 38 % CSS) using Kaplan-Meier survival analyses. TALL score was externally validated in a single-center cohort of 85 UTUC patients., Conclusions: We developed a multivariable prognostic tool for the prediction of oncological outcomes after RNU for high-grade UTUC. The score can be used for patient counseling, selection for adjuvant systemic therapies and design of clinical trials.

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.

Context: The European Association of Urology (EAU) guidelines panel on upper urinary tract urothelial cell carcinoma (UTUC) has prepared updated guidelines to aid clinicians in the current evidence-based management of UTUC and to incorporate recommendations into clinical practice., Objective: To provide a brief overview of the EAU guidelines on UTUC as an aid to clinicians., Evidence Acquisition: The recommendations provided in the current guidelines are based on a thorough review of available UTUC guidelines and articles identified following a systematic search of Medline. Data on urothelial malignancies and UTUC were searched using these keywords: urinary tract cancer; urothelial carcinomas; upper urinary tract, carcinoma; renal pelvis; ureter; bladder cancer; chemotherapy; nephroureterectomy; adjuvant treatment; instillation; neoadjuvant treatment; recurrence; risk factors; and survival. References were weighted by a panel of experts., Evidence Synthesis: Due to the rarity of UTUC, there are insufficient data to provide strong recommendations (ie, grade A). However, the results of recent multicentre studies are now available, and there is a growing interest in UTUC. The 2009 TNM classification is recommended. Recommendations are given for diagnosis and risk stratification as well as radical and conservative treatment, and prognostic factors are discussed. A single postoperative dose of intravesical mitomycin after nephroureterectomy reduces the risk of bladder tumour recurrence. Recommendations are also provided for patient follow-up after different therapeutic strategies., Conclusions: These guidelines contain information on the management of individual patients according to a current standardised approach. Urologists should take into account the specific clinical characteristics of each patient when determining the optimal treatment regimen, based on the proposed risk stratification of these tumours., Patient Summary: Urothelial carcinoma of the upper urinary tract is rare, but because 60% of these tumours are invasive at diagnosis, an appropriate diagnosis is most important. A number of known risk factors exist., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: The impact of cardiopulmonary bypass in level III-IV tumor thrombectomy on surgical and oncologic outcomes is unknown. We determine the impact of cardiopulmonary bypass on overall and cancer specific survival, as well as surgical complication rates and immediate outcomes in patients undergoing nephrectomy and level III-IV tumor thrombectomy with or without cardiopulmonary bypass., Materials and Methods: We retrospectively analyzed 362 patients with renal cell cancer and with level III or IV tumor thrombus from 1992 to 2012 at 22 U.S. and European centers. Cox proportional hazards models were used to compare overall and cancer specific survival between patients with and without cardiopulmonary bypass. Perioperative mortality and complication rates were assessed using logistic regression analyses., Results: Median overall survival was 24.6 months in noncardiopulmonary bypass cases and 26.6 months in cardiopulmonary bypass cases. Overall survival and cancer specific survival did not differ significantly in both groups on univariate analysis or when adjusting for known risk factors. On multivariate analysis no significant differences were seen in hospital length of stay, Clavien 1-4 complication rate, intraoperative or 30-day mortality and cancer specific survival. Limitations include the retrospective nature of the study., Conclusions: In our multi-institutional analysis the use of cardiopulmonary bypass did not significantly impact cancer specific survival or overall survival in patients undergoing nephrectomy and level III or IV tumor thrombectomy. Neither approach was independently associated with increased mortality on multivariate analysis. Greater surgical complications were not independently associated with the use of cardiopulmonary bypass., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Context: There is an ongoing debate about the factors that influence intravesical recurrence (IVR) after radical nephrouretectomy (RNU) to treat upper tract urothelial carcinoma (UTUC)., Objective: To assess significant predictors of IVR after RNU from a systematic review of the literature and meta-analysis., Evidence Acquisition: A computerized bibliographic search of the Medline, Embase, and Cochrane databases was performed for all reports that included detailed results of multivariate analyses on the predictors of IVR. According to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, we selected 18 retrospective studies that each included more than 100 patients treated exclusively with RNU between 2007 and 2014. Cumulative analyses of available hazard ratios (HRs) and their corresponding 95% confidence intervals were conducted using R software to assess the potential predictors of IVR., Evidence Synthesis: Among the 8275 patients included, 2402 (29%) were diagnosed with IVR within a median time of 22.2 mo (range 6.7-56.5). Patient-specific predictors were as follows: male gender (HR 1.37; p<0.001), previous bladder cancer (HR 1.96; p<0.001), and preoperative chronic kidney disease (HR 1.87; p=0.002). Tumor-specific predictors were as follows: positive preoperative urinary cytology (HR 1.56; p<0.001), ureteral location (HR 1.27; p<0.001), multifocality (HR 1.61; p=0.002), invasive pT stage (HR 1.38; p<0.001), and necrosis (HR 2.17; p=0.02). Treatment-specific predictors were as follows: a laparoscopic approach (HR 1.62; p=0.003), extravesical bladder cuff removal (HR 1.22; p=0.02), and positive surgical margins (HR 1.90; p=0.004)., Conclusions: A meta-analysis of available data identified significant predictors of IVR that should be systematically assessed to propose a risk-adapted approach to adjuvant intravesical instillation of chemotherapy and cystoscopic surveillance after RNU., Patient Summary: In this report, we looked at the factors linked to intravesical recurrence after radical nephroureterectomy to treat upper urinary tract urothelial carcinoma. We identified patient-, tumor- and treatment-specific characteristics that should be systematically assessed to guide postoperative decision-making., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Conditional survival (CS) provides better estimates of the survival probability at each follow-up time, and its usefulness has been proven in several solid malignancies., Objective: To assess the changes in 5-yr CS rates after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) and to determine how well-established prognostic factors evolve over time., Design, Setting, and Participants: We analysed data from 3544 patients treated with RNU at 15 international academic centres between 1989 and 2012., Intervention: RNU., Outcomes Measurements and Statistical Analysis: Conditional intravesical recurrence-free (IVRFS), cancer-specific survival (CSS), and overall survival (OS) estimates were calculated using the Kaplan-Meier method. A multivariable Cox regression model was used to calculate proportional hazard ratios for the prediction of mortality., Results and Limitations: The 5-yr bladder cancer recurrence-free survival, CSS, and OS rates were 54.9%, 72.2%, and 62.6%, respectively. Given a 1-, 2-, 3-, and 4-yr survivorship, the 5-yr conditional OS rates improved to 65.2%, 69.3%, 71.5%, and 73.0%, respectively. The 5-yr CS improvement was primarily noted among surviving patients with advanced-stage disease. The impact of pathologic parameters on CS estimates decreased over time for both CSS and OS, whereas the impact of age and gender increased with survivorship. No survival benefit was noted regarding the adjuvant chemotherapy status. Findings were confirmed upon multivariable analyses. Tumour location, the presence of carcinoma in situ, and the type of bladder cuff excision were continuously predictive for IVRFS whatever the survivorship. A limitation is the retrospective design., Conclusions: CS analysis demonstrates that the patient risk profile evolves during the post-RNU follow-up. The probability of survival markedly increases over time in patients having high-stage disease. The impact of prognostic pathologic features decreases over time and can disappear for long-term CS., Patient Summary: In this study, we found that the risk of intravesical recurrence, cancer-specific survival, and overall mortality evolves over the follow-up after surgery. Taking into account the survivorship provides better estimates of the survival probability at each follow-up time., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: Metastatic renal cell carcinoma can be clinically diverse in terms of the pattern of metastatic disease and response to treatment. We studied the impact of metastasis and location on cancer specific survival., Materials and Methods: The records of 2,017 patients with renal cell cancer and tumor thrombus who underwent radical nephrectomy and tumor thrombectomy from 1971 to 2012 at 22 centers in the United States and Europe were analyzed. Number and location of synchronous metastases were compared with respect to patient cancer specific survival. Multivariable Cox regression models were used to quantify the impact of covariates., Results: Lymph node metastasis (155) or distant metastasis (725) was present in 880 (44%) patients. Of the patients with distant disease 385 (53%) had an isolated metastasis. The 5-year cancer specific survival was 51.3% (95% CI 48.6-53.9) for the entire group. On univariable analysis patients with isolated lymph node metastasis had a significantly worse cancer specific survival than those with a solitary distant metastasis. The location of distant metastasis did not have any significant effect on cancer specific survival. On multivariable analysis the presence of lymph node metastasis, isolated distant metastasis and multiple distant metastases were independently associated with cancer specific survival. Moreover higher tumor thrombus level, papillary histology and the use of postoperative systemic therapy were independently associated with worse cancer specific survival., Conclusions: In our multi-institutional series of patients with renal cell cancer who underwent radical nephrectomy and tumor thrombectomy, almost half of the patients had synchronous lymph node or distant organ metastasis. Survival was superior in patients with solitary distant metastasis compared to isolated lymph node disease., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)