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In locally advanced RCC, 6 phase 3 randomized controlled trials (RCTs) were designed in the perioperative setting with immune checkpoint inhibitor (ICI) monotherapy or combinations. Adjuvant trials with atezolizumab, pembrolizumab, and nivolumab with ipilimumab reported results, as did the only perioperative trial with nivolumab. Of these, only 1 year of adjuvant pembrolizumab improved disease-free survival (DFS) versus placebo, with the other trials showing no improvement in DFS. In the purely neoadjuvant setting, phase 1 b/2 ICI trials have demonstrated safety, efficacy, and dynamic changes of immune infiltrates, and provide a rationale for randomized trial concepts., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In KEYNOTE-564, adjuvant pembrolizumab, a PD-1 antibody, significantly improved disease-free survival (DFS) in localised clear-cell renal cell carcinoma (ccRCC) with a high risk of relapse. In 2021, the European Association of Urology RCC Guidelines Panel issued a weak recommendation for adjuvant pembrolizumab for high-risk ccRCC as defined by the trial until final overall survival data and results from other trials were available. Meanwhile, the primary DFS endpoints were not met for adjuvant atezolizumab (PD-L1 inhibitor; IMmotion010), adjuvant nivolumab plus ipilimumab (CheckMate 914), or perioperative nivolumab (PROSPER). Owing to heterogeneity, a meta-analysis is not recommended. Pembrolizumab remains the only immune checkpoint inhibitor currently recommended in this setting. Overall survival data are immature and biomarkers to predict outcome are lacking. Uncertainty exists and overtreatment is occurring. Treatment decisions should be made with caution and with the involvement of each patient. PATIENT SUMMARY: New results from three trials of immunotherapy after surgery for kidney cancer to reduce the risk of recurrence showed no improvement with these treatments. These results are in contrast to an earlier study that showed that the antibody pembrolizumab did extend the time before kidney cancer recurrence, even though it is not yet clear if overall survival is longer. Thus, we cautiously recommend pembrolizumab as additional treatment in high-risk kidney cancer after surgery, but patient preference should be carefully considered and the risk of overtreatment should be discussed., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Retrospective comparative studies suggest a survival benefit after complete local treatment of recurrence (LTR) in renal cell carcinoma (RCC), which may be largely due to an indication bias., Objective: To determine the role of LTR in a homogeneous population characterised by limited and potentially resectable recurrence., Design Setting and Participants: RECUR is a protocol-based multicentre European registry capturing patient and tumour characteristics, risk of recurrence (RoR), recurrence patterns, and survival of those curatively treated for nonmetastatic RCC from 2006 to 2011. Per-protocol resectable disease (RD) recurrence was defined as (1) solitary metastases, (2) oligometastases, or (3) renal fossa or renal recurrence after radical or partial nephrectomy, respectively., Intervention: Local treatment of recurrence., Outcome Measurements and Statistical Analysis: Overall survival (OS) and cancer-specific survival was compared in the RD population that underwent LTR versus no LTR. We constructed a multivariate model to predict risk factors for overall mortality and analysed the effect of LTR across RoR groups., Results and Limitations: Of 3039 patients with localised RCC treated with curative intent, 505 presented with recurrence, including 176 with RD. Of these patients, 97 underwent LTR and 79 no LTR. Patients in the LTR group were younger (64.3 [40-80] vs 69.2 [45-87] yr; p  = 0.001). The median OS was 70.3 mo (95% confidence interval [CI] 58-82.6) versus 27.4 mo (95% CI 23.6-31.15) in the LTR versus no-LTR group ( p  < 0.001). After a multivariate analysis, having LTR (hazard ratio [HR] 0.37 [95% CI 0.2-0.6]), having low- versus high-risk RoR (HR 0.42 [95% CI [0.20-0.83]), and not having extra-abdominal/thoracic metastasis (HR 1.96 [95% CI 1.02-3.77]) were prognostic factors of longer OS. The LTR effect on survival was consistent across risk groups. OS HR for high, intermediate, and low risks were 0.36 (0.2-0.64), 0.27 (0.11-0.65), and 0.26 (0.08-0.8), respectively. Limitations include retrospective design., Conclusions: This is the first study assessing the effectiveness of LTR in RCC in a comparable population with RD. This study supports the role of LTR across all RoR groups., Patient Summary: We assessed the effectiveness of local treatment of resectable recurrent renal cell carcinoma after surgical treatment of the primary kidney tumour. Local treatment of recurrence was associated with longer survival across groups with a risk of recurrence., (© 2022 The Authors.)

Context: The European Association of Urology (EAU) Renal Cell Carcinoma (RCC) Guideline Panel has prepared evidence-based guidelines and recommendations for the management of RCC., Objective: To present a summary of the 2022 RCC guideline, which is based on a standardised methodology including systematic reviews (SRs) and provides transparent and reliable evidence for the management of RCC., Evidence Acquisition: For the 2022 update, a new literature search was carried out with a cutoff date of May 28, 2021, covering the Medline, EMBASE, and Cochrane databases. The data search focused on randomised controlled trials (RCTs) and retrospective or controlled comparator-arm studies, SRs, and meta-analyses. Evidence synthesis was conducted using modified GRADE criteria as outlined for all the EAU guidelines., Evidence Synthesis: All chapters of the RCC guideline were updated on the basis of a structured literature assessment, and clinical practice recommendations were developed. The majority of the studies included were retrospective with matched or unmatched cohorts and were based on single- or multi-institution data or national registries. The exception was systemic treatment of metastatic RCC, for which there are several large RCTs, resulting in recommendations that are based on higher levels of evidence., Conclusions: The 2022 RCC guidelines have been updated by a multidisciplinary panel of experts using the highest methodological standards. These guidelines provide the most reliable contemporary evidence base for the management of RCC in 2022., Patient Summary: The European Association of Urology panel for guidelines on kidney cancer has thoroughly evaluated the research data available to establish up-to-date international standards for the care of patients with kidney cancer., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Context: The current impact of haematuria investigations on health care organisations is significant. There is currently no consensus on how to investigate patients with haematuria., Objective: To evaluate the incidence of bladder cancer, upper tract urothelial carcinoma (UTUC), and renal cell carcinoma (RCC) among patients undergoing investigation for haematuria and identify any risk factors for bladder cancer, UTUC, and RCC (BUR)., Evidence Acquisition: Medline, Embase, and Cochrane controlled trials databases and ClinicalTrials.gov were searched for all relevant publications from January 1, 2000 to June 2021 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Prospective, retrospective, and cross-sectional studies with a minimum population of 50 patients with haematuria were considered for the review., Evidence Synthesis: A total of 44 studies were included. The total number of participants was 229701. The pooled incidence rate for urothelial bladder cancer was 17% (95% confidence interval [CI] 14-20%) for visible haematuria (VH) and 3.3% (95% CI 2.45-4.3%) for nonvisible haematuria (NVH). The pooled incidence rate for RCC was 2% (95% CI 1-2%) for VH and 0.58% (95% CI 0.42-0.77%) for NVH. The pooled incidence rate for UTUC was 0.75% (95% CI 0.4-1.2%) for VH and 0.17% (95% CI 0.081-0.299%) for NVH. On sensitivity analysis, the proportions of males (risk ratio [RR] 1.14, 95% CI 1.10-1.17 for VH; 1.54, 95% CI 1.34-1.78 for NVH; p < 0.00001; moderate certainty evidence) and individuals with a smoking history (RR 1.41, 95% CI 1.24-1.61 for VH; 1.53, 95% CI 1.36-1.72 for NVH; p < 0.00001; moderate certainty evidence) appeared to be higher in BUR than in non-BUR groups., Conclusions: Male gender and smoking history are risk factors for BUR cancer in haematuria, with bladder cancer being the commonest cancer. The incidence of RCC and UTUC in NVH is low. The review serves as a reference standard for future policy-making on investigation of haematuria by global organisations., Patient Summary: Our review shows that male gender and smoking history are risk factors for cancers of the bladder, kidney, and ureter. The review also provides information on the proportion of patients who have cancer when they have blood in their urine (haematuria) and will allow policy-makers to decide on the most appropriate method for investigating haematuria in patients., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

To assess the impact of body mass index (BMI) on peri-operative outcomes of kidney and upper tract robot-assisted surgery. Medical audit of patients who underwent robot-assisted kidney and upper tract cancer surgery at a single institution between 2017 and 2019, categorized on BMI into obese patients with a BMI ≥ 30 kg/m 2 and a control group with BMI < 25 kg/m 2 . Patient and tumour characteristics, surgery time, intraoperative blood loss, intraoperative adverse events (AE) according to the European Association of Urology Intraoperative Adverse Incidents Classification (EAUiaiC), conversion- to-open/radical rate as well as 30-day postoperative AE according to Clavien-Dindo (CD) and length of inpatient stay were analyzed. 366 patients were identified, 141 with a BMI < 25 (normal-weight) and 225 BMI ≥ 30 (obesity). There were no significant differences between the groups in terms of age, gender, comorbidities, tumour size, TNM stage and type of surgery. Obese patients had a higher estimated blood loss (198.05 ml), surgery time (171.75 min), intraoperative AE (all grades) (14.67%, 95% CI (0.10-0.19) as well as adherent perinephric fat (APF) (14.22%, 95% CI (0.09-0.19)) in contrast to the control group (86.85 ml, 148.29 min, 7.04% and 2.12%, respectively). Hospital stay, major intraoperative AE (≥ 3) and major postoperative AE (CD > 2) distributed equally between groups. Robotic kidney and upper tract surgery in obese patients showed an increase in surgery time and blood loss potentially related to APF. However, obesity was not associated with conversion to open surgery or radical nephrectomy in nephron-sparing procedures, length of stay, major intraoperative AE or postoperative complications., (© 2021. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Adjuvant treatment of nonmetastatic high-risk renal cell carcinoma is an unmet medical need. In the past, several tyrosine kinase inhibitor trials have failed to demonstrate an improvement of disease-free survival (DFS) in this setting. Only one trial (S-TRAC) provided evidence for improved DFS with sunitinib but without an overall survival (OS) signal. Keynote-564 is the first trial of an immune checkpoint inhibitor that significantly improved DFS with adjuvant pembrolizumab, a programmed death receptor-1 antibody, in clear cell renal cell carcinoma with a high risk of relapse. The intention-to-treat population, which included a group of patients after metastasectomy and no evidence of disease (M1 NED), had a significant DFS benefit. The OS data are not mature as yet. The Renal Cell Carcinoma Guideline Panel issues a weak recommendation for the adjuvant use of pembrolizumab for high-risk clear cell renal carcinoma, as defined by the trial until final OS data are available. However, the trial reilluminates the discussion on when and in whom metastasectomy should be performed. Here, caution is necessary not to perform metastasectomy in patients with poor prognostic features and rapid progressive disease, which must be excluded by a confirmatory scan of disease status prior to planned metastasectomy. PATIENT SUMMARY: New data from the adjuvant immune checkpoint inhibitor trial with pembrolizumab (a programmed death receptor-1 antibody) for the treatment of high-risk clear cell renal cell carcinoma (ccRCC) after surgery showed that the drug prolonged the period of being cancer free significantly, although whether it prolonged survival remained uncertain. Consequently, pembrolizumab is cautiously recommended as additional (ie, adjuvant) treatment in high-risk ccRCC after kidney cancer surgery., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Following CARMENA and SURTIME, patients with metastatic renal cell carcinoma (mRCC) and International Metastatic RCC Database Consortium (IMDC) intermediate and poor risk receive systemic therapy with the primary tumour (primary) in place, with the option of deferred cytoreductive nephrectomy (CN) in responding patients. We retrospectively analysed the safety and efficacy of first-line nivolumab/ipilimumab in 71 primary mRCC patients (42.3% IMDC poor risk; 43.6% with more than three metastatic sites). The baseline mean primary diameter was 9.3 cm and median follow-up was 11.5 mo. Of 69 patients with at least one follow-up computed tomography scan, 23 (33.3 %) had a partial response (PR) of the primary after a median of 4.8 mo, which was associated with a 91.3% overall response rate at metastatic sites (MSs) and absence of progressive disease, irrespective of the IMDC risk. The complete response (CR) rate at MSs ( n  = 7 [10.1%]) is similar to the CR rate in CheckMate 214. Thirteen deferred CNs were performed (18.8%) after a median of 13 mo, rendering four patients disease free. Only 4.3% of primaries progressed; grade 3-4 immune-related adverse events occurred in 31.9%. Irrespective of the IMDC risk, patients with a PR in the primary had a 1-yr overall survival rate of 89% versus 67% in those without ( p  = 0.012)., Patient Summary: Patients with metastatic kidney cancer receiving immunotherapy with nivolumab and ipilimumab had superior response at metastatic sites and better survival irrespective of International Metastatic RCC Database Consortium (IMDC) risk., (© 2021 The Authors.)

Objective: To analyse the impact of the COVID-19 pandemic on a centralized specialist kidney cancer care pathway., Materials and Methods: We conducted a retrospective analysis of patient and pathway characteristics including prioritization strategies at the Specialist Centre for Kidney Cancer located at the Royal Free London NHS Foundation Trust (RFH) before and during the surge of COVID-19., Results: On 18 March 2020 all elective surgery was halted at RFH to redeploy resources and staff for the COVID-19 surge. Prioritizing of patients according to European Association of Urology guidance was introduced. Clinics and the specialist multidisciplinary team (SMDT) meetings were maintained with physical distancing, kidney surgery was moved to a COVID-protected site, and infection prevention measurements were enforced. During the 7 weeks of lockdown (23 March to 10 May 2020), 234 cases were discussed at the SMDT meetings, 53% compared to the 446 cases discussed in the 7 weeks pre-lockdown. The reduction in referrals was more pronounced for small and asymptomatic renal masses. Of 62 low-priority cancer patients, 27 (43.5%) were deferred. Only one (4%) COVID-19 infection occurred postoperatively, and the patient made a full recovery. No increase in clinical or pathological upstaging could be detected in patients who underwent deferred surgery compared to pre-COVID practice., Conclusion: The first surge of the COVID-19 pandemic severely impacted diagnosis, referral and treatment of kidney cancer at a tertiary referral centre. With a policy of prioritization and COVID-protected pathways, capacity for time-sensitive oncological interventions was maintained and no immediate clinical harm was observed., (© 2021 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

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

Purpose: Radiomics is a specific field of medical research that uses programmable recognition tools to extract objective information from standard images to combine with clinical data, with the aim of improving diagnostic, prognostic, and predictive accuracy beyond standard visual interpretation. We performed a narrative review of radiomic applications that may support improved characterization of small renal masses (SRM). The main focus of the review was to identify and discuss methods which may accurately differentiate benign from malignant renal masses, specifically between renal cell carcinoma (RCC) subtypes and from angiomyolipoma without visible fat (fat-poor AML) and oncocytoma. Furthermore, prediction of grade, sarcomatoid features, and gene mutations would be of importance in terms of potential clinical utility in prognostic stratification and selecting personalised patient management strategies., Methods: A detailed search of original articles was performed using the PubMed-MEDLINE database until 20 September 2020 to identify the English literature relevant to radiomics applications in renal tumour assessment. In total, 42 articles were included in the analysis in 3 main categories related to SRM: prediction of benign versus malignant SRM, subtypes, and nuclear grade, and other features of aggressiveness., Conclusion: Overall, studies reported the superiority of radiomics over expert radiological assessment, but were mainly of retrospective design and therefore of low-quality evidence. However, it is clear that radiomics is an attractive modality that has the potential to improve the non-invasive diagnostic accuracy of SRM imaging and prediction of its natural behaviour. Further prospective validation studies of radiomics are needed to augment management algorithms of SRM., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Objectives: Objective of this study is to report the results of nurse led hematuria clinic service outcome of 2,714 patients., Subjects and Methods: We conducted a retrospective, single center review of 2714 patients with visible and nonvisible hematuria managed by a well-trained nurse specialist in a rapid access clinic (RAC) between 2014 and 2020. All patients received a full review, flexible cystoscopy performed by a nurse, and ultrasound of urinary tracts. After investigations, patients were reassured and discharged or referred for rigid cystoscopy, TURBT, and CT urography., Results: In total, 2714 patients attended the RAC between October 2014 and March 2020. Of these, 1684 (62%) were males and 1030 (38%) females. The median age of patients was 68.3 (IQR 58-79). Of the 1030 females, 500 (48.5%) presented with nonvisible hematuria (NVH), and 530 (51.5%) presented with visible hematuria (VH). The median age was 66 (IQR 56-76). The number of females diagnosed with any form of malignancy was 72 (7% of all females). Of the 1684 males, 288 (17.1%) presented with NVH, and 1396 (82.9%) presented with VH. The median age was 72 (IQR 59-81). The number of males diagnosed with some form of malignancy was 258 (15.3% of all males). Overall, 1926 patients presented with VH and 788 patients presented with NVH. After investigations, 290 patients (15.1%) with VH and 40 (5.1%) patients with NVH had some form of malignancy. The highest number of malignancies found in VH was bladder cancer (n = 222, 11.5%), followed by prostate (n = 28, 1%), renal (n = 23, 0.8%), UT urothelial (n = 17, 0.6%), gynaecological (n = 7, 0.3%), and gastrointestinal (n = 5, 0.2%) cancer. The highest number of pathologies found in NVH was infection (n = 44, 5.6%). Cancer detection rate for symptomatic NVH was more than double that of asymptomatic NVH, 6.5% versus 3.1%, respectively., Conclusion: Overall, 15.1% with VH and 5.1% with NVH present with malignancy. Nurse-led rapid access hematuria clinic and flexible cystoscopy investigation by trained nurse is safe and feasible., Competing Interests: All authors have nothing to disclose., (© 2021 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

Purpose of Review: Immune checkpoint inhibitor (ICI) combination therapy has revolutionized therapy of metastatic renal cancer. The success of immunotherapy has renewed an interest to study these agents in adjuvant and neoadjuvant settings and prior to cytoreductive nephrectomy. This narrative review will give an overview of ongoing trials and early translational research outcomes., Recent Findings: In nonmetastatic renal cell carcinoma (RCC), five phase 3 adjuvant and neoadjuvant trials with ICI monotherapy or combinations are ongoing with atezolizumab (IMmotion 010; NCT03024996), pembrolizumab (KEYNOTE-564; NCT03142334), nivolumab (PROSPER; NCT03055013), nivolumab with or without ipilimumab (CheckMate 914; NCT03138512) and durvalumab with or without tremelimumab (RAMPART; NCT03288532). Phase 1b/2 neoadjuvant trials demonstrate safety, efficacy and dynamic changes of immune infiltrates and provide rationales for neoadjuvant trial concepts as well as prediction of response to therapy. In primary metastatic RCC, two phase 3 trials investigate the role of deferred cytoreductive nephrectomy following pretreatment with ICI combination (NORDICSUN; NCT03977571 and PROBE; NCT04510597)., Summary: The outcomes of the major phase 3 trials are awaited as early as 2023. Meanwhile, translational data from phase 1b/2 studies enhance our understanding of the tumour immune microenvironment and its dynamic changes., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Longer follow-up and new trial data from phase 3 randomised controlled trials investigating immune checkpoint blockade (PD-1 or its ligand PD-L1) in advanced clear-cell renal cell carcinoma (RCC) have recently become available. The CheckMate 9ER trial demonstrated an improved progression-free survival (PFS) and overall survival (OS) benefit for the combination of cabozantinib plus nivolumab. A Keynote-426 update demonstrated an ongoing OS benefit for pembrolizumab plus axitinib in the intention-to-treat population, with a PFS benefit seen across all International Metastatic Database Consortium (IMDC) subgroups, while an update of CheckMate 214 confirmed the long-term benefit of ipilimumab plus nivolumab in IMDC intermediate and poor risk patients. The RCC Guidelines Panel continues to recommend these tyrosine kinase inhibitors + immunotherapy (IO) combination across IMDC risk groups in advanced first-line RCC and dual immunotherapy of ipilimumab and nivolumab in IMDC intermediate and poor risk. PATIENT SUMMARY: New data from trials of immune checkpoint inhibitors for advanced kidney cancer confirm a survival benefit with the combination of cabozantinib plus nivolumab and pembrolizumab plus axitinib and ipilimumab plus nivolumab. These combination therapies are recommended as first-line treatment for advanced kidney cancer., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

The European Association of Urology (EAU) Renal Cell Carcinoma (RCC) Guideline Panel performed a protocol-driven systematic review (SR) on thermal ablation (TA) compared with partial nephrectomy (PN) for T1N0M0 renal masses, in order to provide evidence to support its recommendations. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed, and only comparative studies published between 2000 and 2019 were included. Twenty-six nonrandomised comparative studies were included, recruiting a total of 167 80 patients. Risk of bias (RoB) assessment revealed high or uncertain RoB across all studies, with the vast majority being retrospective, observational studies with poorly matched controls and short follow-up. Limited data showed TA to be safe, but its long-term oncological effectiveness compared with PN remains uncertain. A quality assessment of pre-existing SRs (n=11) on the topic, using AMSTAR, revealed that all SRs had low confidence rating, with all but two SRs being rated critically low. In conclusion, the current data are inadequate to make any strong and clear conclusions regarding the clinical effectiveness of TA for treating T1N0M0 renal masses compared with PN. Therefore, TA may be cautiously considered an alternative to PN for T1N0M0 renal masses, but patients must be counselled carefully regarding the prevailing uncertainties. We recommend specific steps to improve the evidence base based on robust primary and secondary studies. PATIENT SUMMARY: In this report, we looked at the literature to determine the effectiveness of thermoablation (TA) in the treatment of small kidney tumours compared with surgical removal. We found that TA could cautiously be offered as an option due to many remaining uncertainties regarding its effectiveness., (Copyright © 2020. Published by Elsevier B.V.)

Introduction and Objective: Adjuvant studies with checkpoint inhibitors have attracted new interest in accurate pathological lymph node (LN) staging in renal cell carcinoma. Sentinel lymph node (SN) studies in cN0 patients revealed the pattern of lymphatic radiotracer drainage from renal tumors. The aim of this study was to describe the location of single- or oligometastatic LN and analyze if the topography of these first landing sites matches the drainage pattern observed in SN studies of renal tumors., Materials and Methods: We collected data from 8 referral centers from 1990 to 2018 of all patients with pT1-4 cN0 or cN1 M0 renal cell carcinoma with pathologically confirmed single- or oligometastases in locoregional LN. The location of LN metastases, number, size of metastatic LN, and survival were analyzed using descriptive statistics with SPSS version 22 (IBM, Chicago, IL)., Results: From 3,794 patients with histologically confirmed pN1, a total of 76 patients (2%) with single- or oligometastatic pN1 were identified, of whom 24 (31.6%) and 52 (68.4%) were cN0 and cN1, respectively. On the left side, LN metastases were predominantly located in the para-aortal (48.0%; 95% confidence interval [CI] 29.22-63.12%) and hilar (31.42%; 95% CI 17.4-49.4%) area. On the right side, metastases located in retrocaval (26.82%; 95% CI 14.7-43.2%), hilar (26.82%; 95% CI 14.7-43.2%), interaortocaval (26.82%; 95% CI 14.7-43.2%), and paracaval (17.07%; 95% CI 7.6-32.6%) LNs. These landing sites exactly matched the lymphatic drainage pattern of intratumorally injected radiotracer reported in SN studies for both sides., Conclusions: Single- or oligometastatic LNs in renal cancer are mainly located in the hilar, retro-, para, and interaortocaval region on the right side and para-aortal region on the left side. These first landing sites match the drainage pattern reported in SN trials., (Copyright © 2019. Published by Elsevier Inc.)

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

Context: Little is known about the natural history of sporadic angiomyolipomas (AMLs); there is uncertainty regarding the indications of treatment and treatment options., Objective: To evaluate the indications, effectiveness, harms, and follow-up of different management modalities for sporadic AML to provide guidance for clinical practice., Evidence Acquisition: A systematic review of the literature was undertaken, incorporating Medline, Embase, and the Cochrane Library (from 1 January 1990 to 30 June 2017), in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. No restriction on study design was imposed. Patients with sporadic AML were included. The main interventions included active surveillance, surgery (nephron-sparing surgery and radical nephrectomy), selective arterial embolisation, and percutaneous or laparoscopic thermal ablations (radiofrequency, microwaves, or cryoablation). The outcomes included indications for active treatment, AML growth rate, AML recurrence rate, risk of bleeding, post-treatment renal function, adverse events of treatments, and modalities of follow-up. Risk of bias assessment was performed using standard Cochrane methods., Evidence Synthesis: Among 2704 articles identified, 43 were eligible for inclusion (zero randomised controlled trials, nine nonrandomised comparative retrospective studies, and 34 single-arm case series). Most studies were retrospective and uncontrolled, and had a moderate to high risk of bias., Conclusions: In active surveillance series, spontaneous bleeding was reported in 2% of patients and active treatment was undertaken in 5%. Active surveillance is the most chosen option in 48% of the cases, followed by surgery in 31% and selective arterial embolisation in 17% of the cases. Selective arterial embolisation appeared to reduce AML volume but required secondary treatment in 30% of the cases. Surgery (particularly nephron-sparing surgery) was the most effective treatment in terms of recurrence and need for secondary procedures. Thermal ablation was an infrequent option. The association between AML size and the risk of bleeding remained unclear; as such the traditional 4-cm cut-off should not per se trigger active treatment. In spite of the limitations and uncertainties relating to the evidence base, the findings may be used to guide and inform clinical practice, until more robust data emerge., Patient Summary: Sporadic angiomyolipoma (AML) is a benign tumour of the kidney consisting of a mixture of blood vessels, fat, and muscle. Large tumours may have a risk of spontaneous bleeding. However, the size beyond which these tumours need to be treated remains unclear. Most small AMLs can be monitored without any active treatment. For those who need treatment, options include surgical removal of the tumour or stopping its blood supply (selective embolisation). Surgery has a lower recurrence rate and lower need for a repeat surgical procedure., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose of Review: Over the past few years the treatment options for renal cell cancer (RCC) have rapidly evolved. Even in the setting of metastatic disease, a consistent component of treatment in RCC patients has been cytoreductive nephrectomy based on the results of research carried out over a decade ago. Despite huge shifts in systemic treatment modalities, cytoreductive nephrectomy continued to be recommended despite a lack of evidence for its use in metastatic RCC in those patients receiving state-of-the-art therapies., Recent Findings: To address the lack of evidence, two recent trials [Cancer du Rein Metastatique Nephrectomie et Antiangioge[Combining Acute Accent]niques (CARMENA) and SURTIME] sought to assess the role and sequence of cytoreductive nephrectomy in metastatic RCC patients receiving vascular endothelial growth factor-targeted tyrosine kinase inhibitor treatment. The results of one of these trials, namely CARMENA, demonstrated no benefit of cytoreductive nephrectomy when used in combination with the vascular endothelial growth factor-targeted tyrosine kinase inhibitor Sunitinib. However, with further developments in medical treatment and questions regarding the specific methods of the trial - do these results change everything for the role of cytoreductive nephrectomy?, Summary: While the results from CARMENA and SURTIME are not conclusive, they suggest that those patients with advanced disease requiring systemic therapy should indeed receive this first prior to any cytoreductive nephrectomy.

The two recent prospective randomized trials CARMENA and SURTIME have changed the therapy paradigm of metastatic renal cell carcinoma. The CARMENA trial was conducted to investigate whether cytoreductive nephrectomy (CN) is required in the targeted therapy area, whereas SURTIME studied whether deferred CN in combination with sunitinib can be used to identify patients with inherent targeted therapy resistance. In the current review, we provide a comprehensive discussion of two randomized studies and the current evidence with up-do-date algorithms for treating primary metastatic clear-cell renal cell carcinoma in the era of targeted therapy and immune-checkpoint inhibition., Competing Interests: Conflict of interest statement: Axel Bex took part in advisory boards of Pfizer, Novartis, Ipsen, Eisai and Roche. He is the Principal Investigator of the EORTC SURTIME trial sponsored in part by a grant from Pfizer to the EORTC. Thomas Powles received honoraria from Bristol-Myers Squibb, MERCK, and Roche/Genentech; has consulting or advisory roles at AstraZeneca, Bristol-Myers Squibb, Genentech/Roche, Merck, and Novartis; received research funding from AstraZeneca/MedImmune and Roche/Genentech; and has other relationships with Bristol-Myers Squibb and Ipsen., (© The Author(s), 2019.)

Recent randomised trials have demonstrated a survival benefit for a front-line ipilimumab and nivolumab combination therapy, and pembrolizumab and axitinib combination therapy in metastatic clear-cell renal cell carcinoma. The European Association of Urology Guidelines Panel has updated its recommendations based on these studies. PATIENT SUMMARY: Pembrolizumab plus axitinib is a new standard of care for patients diagnosed with kidney cancer spread outside the kidney and who did not receive any prior treatment for their cancer (treatment naïve). This applies to all risk groups as determined by the International Metastatic Renal Cell Carcinoma Database Consortium criteria., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To understand uncertainties and knowledge gaps regarding lymphatic drainage in renal tumors, we performed 2 prospective studies to demonstrate regional lymph node (LN) drainage with sentinel lymph node (SN) imaging and biopsy. Here, we report the technique and perioperative safety of retroperitoneal SN dissection with different surgical approaches., Methods: Seventy three patients from the 2 trials were included in the analysis. Patients had cT1-2N0M0 renal tumors (