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Background and Objective: Immune checkpoint inhibitors (ICIs) and antibody-drug conjugates (ADCs) herald a transformative era in metastatic renal cell carcinoma (RCC) and transitional cell carcinoma (TCC) treatment, amid acknowledged sex-based disparities in these cancers. We conducted a systematic review and network meta-analysis (NMA) to identify sex-specific differences in the efficacy of ICI/ADC monotherapy or combination therapies for RCC and TCC survival, in metastatic and adjuvant settings., Methods: A systematic search was conducted up to October 2023 for English articles on ICIs and ADCs as systemic therapies (ICIs in first-line and adjuvant treatment for RCC, ICIs and ADCs in first- and second-line treatment for TCC). Randomised clinical trials were considered. The primary objective was overall survival (OS) of ICIs and ADCs between males and females. The secondary outcomes included progression-free survival, overall response rate, disease-free survival, and recurrence-free survival. Treatment efficacy was evaluated by sex via odds ratios (ORs) and confidence intervals compared with controls. Log ORs were used for creating a frequentist NMA. This meta-analysis was registered on PROSPERO (CRD42023468632)., Key Findings and Limitations: Eighteen articles met the inclusion criteria. Females had an advantage for RCC-adjuvant treatment for atezolizumab (log OR [SE] = -0.57 ± 0.25, p = 0.024) in OS. Males showed a survival advantage in TCC second-line treatment for ADC-Nectin 4 (log OR [SE] = 0.65 ± 0.28, p = 0.02). No other significant results were shown., Conclusions and Clinical Implications: The NMA revealed gender-specific variations in ICI and ADC responses for RCC and TCC, offering insights for personalised cancer care and addressing disparities in cancer care and outcomes., Patient Summary: In this systematic review, we looked at the sex differences for metastatic renal cell carcinoma (RCC) and transitional cell carcinoma (TCC) for antibody-drug conjugates and immune checkpoint inhibitors. In our analysis, female and male sex has better overall survival for adjuvant and second-line therapies for RCC and TCC, respectively. Urgent research on gender-specific cancer therapies is imperative., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background and Objective: The role of cytoreductive nephrectomy (CN) in the treatment of metastatic renal cell carcinoma (mRCC) has been called into question on the basis of clinical trial data from the tyrosine kinase inhibitor (TKI) era. Comparative analyses of CN for patients treated with immuno-oncology (IO) versus TKI agents are sparse. Our objective was to compare CN timing and outcomes among patients who received TKI versus IO therapy., Methods: This was a multicenter retrospective analysis of patients who underwent CN using data from the REMARCC (Registry of Metastatic RCC) database. The cohort was divided into TKI versus IO first-line therapy groups. The primary outcome was all-cause mortality (ACM). Secondary outcomes included cancer-specific mortality (CSM). Multivariable analysis was used to identify factors predictive for ACM and CSM. The Kaplan-Meier method was used to analyze 5-yr overall survival (OS) and cancer-specific survival (CSS) with stratification by primary systemic therapy and timing in relation to CN., Key Findings and Limitations: We analyzed data for 189 patients (148 TKI + CN, 41 IO +CN; median follow-up 23.2 mo). Multivariable analysis revealed that a greater number of metastases (hazard ratio [HR] 1.06; p = 0.015), greater primary tumor size (HR 1.10; p  = 0.043), TKI receipt (HR 2.36; p  = 0.015), and initiation of systemic therapy after CN (HR 1.49; p  = 0.039) were associated with worse ACM. A greater number of metastases at diagnosis (HR 1.07; p  = 0.011), greater primary tumor size (HR 1.12; p  = 0.018), TKI receipt (HR 5.43; p  = 0.004), and initiation of systemic therapy after CN (HR 2.04; p  < 0.001) were associated with worse CSM. Kaplan-Meier analyses revealed greater 5-yr rates for OS (51% vs 27%; p  < 0.001) and CSS (83% vs 30%; p  < 0.001) for IO +CN versus TKI + CN. This difference persisted in a subgroup analysis for patients with intermediate or poor risk, with 5-yr OS rates of 50% for IO + CN versus 30% for TKI + CN ( p  < 0.001). A subanalysis stratified by CN timing revealed better 5-yr rates for OS (50% vs 30%; p  = 0.042) and CSS (90% vs 30%, p  = 0.019) for delayed CN after IO therapy, but not after TKI therapy., Conclusions and Clinical Implications: For patients who underwent CN, systemic therapy before CN was associated with better outcomes. In addition, IO therapy was associated with better survival outcomes in comparison to TKI therapy. Our findings question the applicability of clinical trial data from the TKI era to CN in the IO era for mRCC., Patient Summary: For patients with metastatic kidney cancer treated with surgery, better survival outcomes were observed for those who also received immunotherapy in comparison to therapy targeting specific proteins in the body (tyrosine kinase inhibitors, TKIs). Immunotherapy or TKI treatment resulted in better outcomes if it was received before rather than after surgery., (© 2024 Published by Elsevier B.V. on behalf of European Association of Urology.)

Background: Further stratification of the risk of recurrence of clear-cell renal cell carcinoma (ccRCC) with venous tumor thrombus (VTT) will facilitate selection of candidates for adjuvant therapy., Objective: To assess the impact of tumor grade discrepancy (GD) between the primary tumor (PT) and VTT in nonmetastatic ccRCC on disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS)., Design, Setting, and Participants: This was a retrospective analysis of a multi-institutional nationwide data set for patients with pT3N0M0 ccRCC who underwent radical nephrectomy and thrombectomy., Outcomes Measurements and Statistical Analysis: Pathology slides were centrally reviewed. GD, a bidirectional variable (upgrading or downgrading), was numerically defined as the VTT grade minus the PT grade. Multivariable models were built to predict DFS, OS, and CSS., Results and Limitations: We analyzed data for 604 patients with median follow-up of 42 mo (excluding events). Tumor GD between VTT and PT was observed for 47% (285/604) of the patients and was an independent risk factor with incremental value in predicting the outcomes of interest (all p < 0.05). Incorporation of tumor GD significantly improved the performance of the ECOG-ACRIN 2805 (ASSURE) model. A GD-based model (PT grade, GD, pT stage, PT sarcomatoid features, fat invasion, and VTT consistency) had a c index of 0.72 for DFS. The hazard ratios were 8.0 for GD = +2 (p < 0.001), 1.9 for GD = +1 (p < 0.001), 0.57 for GD = -1 (p = 0.001), and 0.22 for GD = -2 (p = 0.003) versus GD = 0 as the reference. According to model-converted risk scores, DFS, OS, and CSS significantly differed between subgroups with low, intermediate, and high risk (all p < 0.001)., Conclusions: Routine reporting of VTT upgrading or downgrading in relation to the PT and use of our GD-based nomograms can facilitate more informed treatment decisions by tailoring strategies to an individual patient's risk of progression., Patient Summary: We developed a tool to improve patient counseling and guide decision-making on other therapies in addition to surgery for patients with the clear-cell type of kidney cancer and tumor invasion of a vein., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Context: The resection technique used to excise tumor during robotic partial nephrectomy (RPN) is of paramount importance in achieving optimal clinical outcomes., Objective: To provide an overview of the different resection techniques used during RPN, and a pooled analysis of comparative studies., Evidence Acquisition: The systematic review was conducted according to established principles (PROSPERO: CRD42022371640) on November 7, 2022. A population (P: adult patients undergoing RPN), intervention (I: enucleation), comparator (C: enucleoresection or wedge resection), outcome (O: outcome measurements of interest), and study design (S) framework was prespecified to assess study eligibility. Studies reporting a detailed description of resection techniques and/or evaluating the impact of resection technique on outcomes of surgery were included., Evidence Synthesis: Resection techniques used during RPN can be broadly classified as resection (non-anatomic) or enucleation (anatomic). A standardized definition for these is lacking. Out of 20 studies retrieved, nine compared "standard" resection versus enucleation. A pooled analysis did not reveal significant differences in terms of operative time, ischemia time, blood loss, transfusions, or positive margins. Significant differences favoring enucleation were found for clamping management (odds ratio [OR] for renal artery clamping 3.51, 95% confidence interval [CI] 1.13-10.88; p  = 0.03), overall complications (OR for occurrence 0.55, 95% CI 0.34-0.87; p  = 0.01) major complications (OR for occurrence 0.39, 95% CI 0.19-0.79; p  = 0.009), length of stay (weighted mean difference [WMD] -0.72 d, 95% CI -0.99 to -0.45; p  < 0.001), and decrease in estimated glomerular filtration rate (WMD -2.64 ml/min, 95% CI -5.15 to -0.12; p  = 0.04)., Conclusions: There is heterogeneity in the reporting of resection techniques used during RPN. The urological community must improve the quality of reporting and research produced accordingly. Positive margins are not specifically related to the resection technique. Focusing on studies comparing standard resection versus enucleation, advantages with tumor enucleation in terms of avoidance of artery clamping, overall/major complications, length of stay, and renal function were found. These data should be considered when planning the RPN resection strategy., Patient Summary: We reviewed studies on robotic surgery for partial kidney removal using different techniques to cut away the kidney tumor. We found that a technique called "enucleation" was associated with similar cancer control outcomes in comparison to the standard technique and had fewer complications, better kidney function after surgery, and a shorter hospital stay., (© 2023 The Authors.)

Context: A variety of models predicting postoperative renal function following surgery for nonmetastatic renal tumors have been reported, but their validity and clinical usefulness have not been formally assessed., Objective: To summarize prediction models available for estimation of mid- to long-term (>3 mo) postoperative renal function after partial nephrectomy (PN) or radical nephrectomy (RN) for nonmetastatic renal masses that include only preoperative or modifiable intraoperative variables., Evidence Acquisition: A systematic review of the English-language literature was conducted using the MEDLINE, Embase, and Web of Science databases from January 2000 to March 2022 according to the PRISMA guidelines (PROSPERO ID: CRD42022303492). Risk of bias was assessed according to the Prediction Model Study Risk of Bias Assessment Tool., Evidence Synthesis: Overall, 21 prediction models from 18 studies were included (nine for PN only; eight for RN only; four for PN or RN). Most studies relied on retrospective patient cohorts and had a high risk of bias and high concern regarding the overall applicability of the proposed model. Patient-, kidney-, surgery-, tumor-, and provider-related factors were included among the predictors in 95%, 86%, 100%, 61%, and 0% of the models, respectively. All but one model included both patient age and preoperative renal function, while only a few took into account patient gender, race, comorbidities, tumor size/complexity, and surgical approach. There was significant heterogeneity in both the model building strategy and the performance metrics reported. Five studies reported external validation of six models, while three assessed their clinical usefulness using decision curve analysis., Conclusions: Several models are available for predicting postoperative renal function after kidney cancer surgery. Most of these are not ready for routine clinical practice, while a few have been externally validated and might be of value for patients and clinicians., Patient Summary: We reviewed the tools available for predicting kidney function after partial or total surgical removal of a kidney for nonmetastatic cancer. Most of the models include patient and kidney characteristics such as age, comorbidities, and preoperative kidney function, and a few also include tumor characteristics and intraoperative variables. Some models have been validated by additional research groups and appear promising for improving counseling for patients with nonmetastatic cancer who are candidates for surgery., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

We describe the case of a 71-yr-old woman with locally advanced muscle-invasive bladder cancer and stage III chronic kidney disease due to an obstructed nonfunctional left kidney. She was started on neoadjuvant immunotherapy, but had to stop treatment because of acute worsening of renal function. Radical cystectomy was then performed uneventfully, revealing pT3aN1 urothelial carcinoma of the bladder. Adjuvant chemotherapy in high-risk locally advanced bladder cancer after radical cystectomy currently poses several challenges, especially for cisplatin-ineligible candidates. Recent data on adjuvant immunotherapy trials suggest a disease-free survival advantage for this subgroup of patients. The current and future role of immuno-oncology agents in this setting is discussed. PATIENT SUMMARY: Patients with advanced bladder cancer might benefit from further chemotherapy or immunotherapy following bladder removal, but it is still unclear which patients benefit the most from this strategy. Measurement of biomarkers and scans to show urinary function will probably help in optimising patient selection for this treatment in the near future., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

A trend towards greater benefit from adjuvant chemotherapy (ACT) in pN+ bladder cancer (BCa) has been observed in multiple randomized controlled trials. However, it is still unclear which patients might benefit the most from this approach. We retrospectively analyzed a multicenter cohort of 1381 patients with pTany pN1-3 cM0 R0 urothelial BCa treated with radical cystectomy (RC) with or without cisplatin-based ACT. The main endpoint was overall survival (OS) after RC. We performed 1:1 propensity score matching to adjust for baseline characteristics and conducted a classification and regression tree (CART) analysis to assess postoperative risk groups and Cox regression analyses to predict OS. Overall, 391 patients (28%) received cisplatin-based ACT. After matching, two cohorts of 281 patients with pN+ BCa were obtained. CART analysis stratified patients into three risk groups: favorable prognosis (≤pT2 and positive lymph node [PLN] count ≤2; odds ratio [OR] 0.43), intermediate prognosis (≥pT3 and PLN count ≤2; OR 0.92), and poor prognosis (pTany and PLN count ≥3; OR 1.36). Only patients with poor prognosis benefitted from ACT in terms of OS (HR 0.51; p < 0.001). We created the first algorithm that stratifies patients with pN+ BCa into prognostic classes and identified patients with pTany BCa with PLN ≥3 as the most suitable candidates for cisplatin-based ACT. PATIENT SUMMARY: We found that overall survival among patients with bladder cancer and evidence of lymph node involvement depends on cancer stage and the number of positive lymph nodes. Patients with more than three nodes affected by metastases seem to experience the greatest overall survival benefit from cisplatin-based chemotherapy after bladder removal. Our study suggests that patients with the highest risk should be prioritized for cisplatin-based chemotherapy after bladder removal., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Literature lacks clear evidence regarding the optimal treatment for non-muscle-invasive micropapillary bladder cancer (MPBC) due to its rarity and the presence of only small sample size and single-centre studies., Objective: To assess cancer-specific mortality (CSM) and overall mortality (OM) between immediate radical cystectomy (RC) and conservative management among T1 high-grade (HG) MPBC., Design, Setting, and Participants: We retrospectively analysed a multicentre dataset including 119 T1 HG MPBC patients treated between 2005 and 2019 at 15 tertiary referral centres. The median follow-up time was 35 mo (interquartile range: 19-64)., Intervention: Patients underwent immediate RC versus conservative management with bacillus Calmette-Guérin., Outcomes Measurements and Statistical Analysis: Cumulative incidence functions and Kaplan-Meier methods were applied to estimate survival outcomes. Multivariable Cox analyses were performed to assess independent predictors of disease recurrence and disease progression after conservative management; covariates consisted of pure MPBC, concomitant lymphovascular invasion (LVI), and carcinoma in situ at initial diagnosis., Results and Limitations: Immediate RC and conservative management were performed in 27% and 73% of patients, respectively. CSM and OM did not differ significantly among patient treated with immediate RC versus conservative management (Pepe-Mori test p = 0.5 and log-rank test p = 0.9, respectively). Overall, 66.7% and 34.5% of patients experienced disease recurrence and disease progression after conservative management, respectively. At multivariable Cox analyses, concomitant LVI was an independent predictor of disease recurrence (p = 0.01) and progression (p = 0.03), while pure MPBC was independently associated with disease progression (p = 0.03). The absence of a centralised re-review and the retrospective design represent the main limitations of our study., Conclusions: Conservative management could achieve satisfactory results among T1 HG MPBC patients with neither pure MPBC nor LVI at initial diagnosis., Patient Summary: Bacillus Calmette-Guérin seems to be an effective therapy for T1 micropapillary bladder cancer patients with neither pure micropapillary disease nor lymphovascular invasion at initial diagnosis., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: The European Association of Urology risk stratification dichotomizes patients with upper tract urothelial carcinoma (UTUC) into two risk categories., Objective: To evaluate the predictive value of a new classification to better risk stratify patients eligible for kidney-sparing surgery (KSS)., Design, Setting, and Participants: This was a retrospective study including 1214 patients from 21 centers who underwent ureterorenoscopy (URS) with biopsy followed by radical nephroureterectomy (RNU) for nonmetastatic UTUC between 2000 and 2017., Outcome Measurements and Statistical Analysis: A multivariate logistic regression analysis identified predictors of muscle invasion (≥pT2) at RNU. The Youden index was used to identify cutoff points., Results and Limitations: A total of 811 patients (67%) were male and the median age was 71 yr (interquartile range 63-77). The presence of non-organ-confined disease on preoperative imaging (p < 0.0001), sessile tumor (p < 0.0001), hydronephrosis (p = 0.0003), high-grade cytology (p = 0.0043), or biopsy (p = 0.0174) and higher age at diagnosis (p = 0.029) were independently associated with ≥pT2 at RNU. Tumor size was significantly associated with ≥pT2 disease only in univariate analysis with a cutoff of 2 cm. Tumor size and all significant categorical variables defined the high-risk category. Tumor multifocality and a history of radical cystectomy help to dichotomize between low-risk and intermediate-risk categories. The odds ratio for muscle invasion were 5.5 (95% confidence interval [CI] 1.3-24.0; p = 0.023) for intermediate risk versus low risk, and 12.7 (95% CI 3.0-54.5; p = 0.0006) for high risk versus low risk. Limitations include the retrospective design and selection bias (all patients underwent RNU)., Conclusions: Patients with low-risk UTUC represent ideal candidates for KSS, while some patients with intermediate-risk UTUC may also be considered. This classification needs further prospective validation and may help stratification in clinical trial design., Patient Summary: We investigated factors predicting stage 2 or greater cancer of the upper urinary tract at the time of surgery for ureter and kidney removal and designed a new risk stratification. Patients with low or intermediate risk may be eligible for kidney-sparing surgery with close follow-up. Our classification scheme needs further validation based on cancer outcomes., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) is associated with improved overall and cancer-specific survival. The post-NAC pathological stage has previously been reported to be a major determinant of outcome., Objective: To develop a postoperative nomogram for survival based on pathological and clinical parameters from an international consortium., Design, Setting, and Participants: Between 2000 and 2015, 1866 patients with MIBC were treated at 19 institutions in the USA, Canada, and Europe. Analysis was limited to 640 patients with adequate follow-up who had received three or more cycles of NAC., Outcome Measurements and Statistical Analysis: A nomogram for bladder cancer-specific mortality (BCSM) was developed by multivariable Cox regression analysis. Decision curve analysis was used to assess the model's clinical utility., Results and Limitations: A total of 640 patients were identified. Downstaging to non-MIBC (ypT1, ypTa, and ypTis) occurred in 271 patients (42 %), and 113 (17 %) achieved a complete response (ypT0N0). The 5-yr BCSM was 47.2 % (95 % confidence interval [CI]: 41.2-52.6 %). On multivariable analysis, covariates with a statistically significant association with BCSM were lymph node metastasis (hazard ratio [HR] 1.90 [95% CI: 1.4-2.6]; p < 0.001), positive surgical margins (HR 2.01 [95 % CI: 1.3-2.9]; p < 0.001), and pathological stage (with ypT0/Tis/Ta/T1 as reference: ypT2 [HR 2.77 {95 % CI: 1.7-4.6}; p < 0.001] and ypT3-4 [HR 5.9 {95 % CI: 3.8-9.3}; p < 0.001]). The area under the curve of the model predicting 5-yr BCSM after cross validation with 300 bootstraps was 75.4 % (95 % CI: 68.1-82.6 %). Decision curve analyses showed a modest net benefit for the use of the BCSM nomogram in the current cohort compared with the use of American Joint Committee on Cancer staging alone. Limitations include the retrospective study design and the lack of central pathology., Conclusions: We have developed and internally validated a nomogram predicting BCSM after NAC and radical cystectomy for MIBC. The nomogram will be useful for patient counseling and in the identification of patients at high risk for BCSM suitable for enrollment in clinical trials of adjuvant therapy., Patient Summary: In this report, we looked at the outcomes of patients with muscle-invasive bladder cancer in a large multi-institutional population. We found that we can accurately predict death after radical surgical treatment in patients treated with chemotherapy before surgery. We conclude that the pathological report provides key factors for determining survival probability., (Copyright © 2020. Published by Elsevier B.V.)

This case presents a 68-yr-old female patient with primary metastatic nonclear renal cell carcinoma (RCC) with multiple bone lesions. The patient underwent a single resection of skull bone lesion (diagnostic for poorly differentiated carcinoma of unknown origin) and cytoreductive nephrectomy. The pathology of the kidney specimen demonstrated an oncocytic papillary RCC. Within 3 mo, she developed skeletal progressive disease and was started on systemic therapy (sunitinib). After initial stabilization, bone metastasis progressed during the third cycle of sunitinib and required second-line therapy (cabozantinib). One of the major unmet needs in non-clear cell RCC is the lack of specific systemic therapy. Data on immunotherapy are still limited. Inclusion of these patients in clinical trials is strongly recommended. PATIENT SUMMARY: Patients with metastatic kidney cancer who present with the less common histological subtype (non-clear cell) have poor survival. In this case, the patient responded to second-line therapy. Very few therapies provide response to treatment. Patients should be offered participation in clinical trials testing combinations with immunotherapy., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Context: Predictors of upstaging from cT1 to pT3a renal masses are poorly inquired, and this remains an area of controversial findings., Objective: To evaluate predictors and outcomes of upstaging from cT1 to pT3a in patients undergoing surgical removal of a renal tumor., Evidence Acquisition: A systematic literature search was performed to identify relevant articles using three electronic engines (PubMed, Embase, and Web of Science). Only studies looking at upstaging to pT3a in patients undergoing either partial nephrectomy (PN) or radical nephrectomy (RN) for cT1 renal tumor were included. Study selection was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement., Evidence Synthesis: Thirteen studies, including 21869 patients (cT1/pT3a: 1256 [5.7%]; cT1/pT1: 20613 [93.3%]), were identified. Patients in the upstaged group were older (weighted mean difference [WMD]: 3.89; p < 0.00001) and mostly male (odds ratio [OR]: 1.23; p = 0.04). Renal tumors were larger (WMD: 0.98; p < 0.00001), more complex (OR: 2.38; p < 0.0001), and with a higher rate of cT1b masses (OR: 3.36; p < 0.00001). The cT1/pT3a group had a higher rate of other renal cell carcinoma histological subtypes (OR: 1.59; p = 0.04), as well as higher odds of Fuhrman grade ≥3 (OR: 2.57; p < 0.00001) and positive surgical margins (OR: 1.85; p = 0.007). Five-year recurrence-free survival (RFS) was worse in the upstaged group (OR: 0.31; p = 0.02). Age (OR: 1.03; p < 0.00001), tumor size (OR: 1.51; p < 0.00001), and RENAL score (OR: 2.80; p = 0.0004) were predictors of upstaging. Upstaging was associated with overall survival (hazard ratio [HR]: 1.94; p = 0.05), cancer-specific survival (HR: 2.24; p = 0.007), and RFS (HR: 2.17; p < 0.00001)., Conclusions: Upstaging to pT3a in case of surgical removal of a cT1 renal tumor is an uncommon event, which however can translate into worse oncological outcomes. Both patient (older age) and tumor (larger size and higher complexity) characteristics are associated with a higher risk of upstaging. There is very limited evidence regarding whether RN would be better than PN in these cases. There remains an unmet need for tools to better characterize renal masses in the preoperative setting., Patients Summary: About 6% of surgically treated localized renal tumors can be found to be locally advanced on final pathology after surgery. This "upstaging" can translate into worse oncological outcomes. There are patient and tumor characteristics that are associated with an increased the risk of upstaging., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Selection of patients for upfront cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) has to be improved., Objective: To evaluate a new scoring system for the prediction of overall mortality (OM) in mRCC patients undergoing CN., Design, Setting, and Participants: We identified a total of 519 patients with synchronous mRCC undergoing CN between 2005 and 2019 from a multi-institutional registry (Registry for Metastatic RCC [REMARCC])., Outcome Measurements and Statistical Analysis: Cox proportional hazard regression was used to test the main predictors of OM. Restricted mean survival time was estimated as a measure of the average overall survival time up to 36 mo of follow-up. The concordance index (C-index) was used to determine the model's discrimination. Decision curve analyses were used to compare the net benefit from the REMARCC model with International mRCC Database Consortium (IMDC) or Memorial Sloan Kettering Cancer Center (MSKCC) risk scores., Results and Limitations: The median follow-up period was 18 mo (interquartile range: 5.9-39.7). Our models showed lower mortality rates in obese patients (p = 0.007). Higher OM rates were recorded in those with bone (p = 0.010), liver (p = 0.002), and lung metastases (p < 0.001). Those with poor performance status (<80%) and those with more than three metastases had also higher OM rates (p = 0.026 and 0.040, respectively). The C-index of the REMARCC model was higher than that of the MSKCC and IMDC models (66.4% vs 60.4% vs 60.3%). After stratification, 113 (22.0%) patients were classified to have a favorable (no risk factors), 202 (39.5%) an intermediate (one or two risk factors), and 197 (38.5%) a poor (more than two risk factors) prognosis. Moreover, 72 (17.2%) and 51 (13.9%) patients classified as having an intermediate and a poor prognosis according to MSKCC and IMDC categories, respectively, would be reclassified as having a good prognosis according to the REMARCC score., Conclusions: Our findings confirm the relevance of tumor and patient features for the risk stratification of mRCC patients and clinical decision-making regarding CN. Further prospective external validations are required for the scoring system proposed herein., Patient Summary: Current stratification systems for selecting patients for kidney removal when metastatic disease is shown are controversial. We suggest a system that includes tumor and patient features besides the systems already in use, which are based on blood tests., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Partial nephrectomy (PN) in elderly patients is underutilized with concerns regarding risk of complications and potential for poor outcomes., Objective: To evaluate quality and functional outcomes of PN in patients >75 yr using trifecta as a composite outcome of surgical quality., Design, Setting, and Participants: Multicenter retrospective analysis of 653 patients aged >75 yr who underwent PN (REnal SURGery in Elderly [RESURGE] Group)., Intervention: PN., Outcome Measurements and Statistical Analysis: Primary outcome was achievement of trifecta (negative margin, no major [Clavien ≥3] urological complications, and ≥90% estimated glomerular filtration rate [eGFR] recovery). Secondary outcomes included chronic kidney disease (CKD) stage III and CKD upstaging. Multivariable analysis (MVA) was used to assess variables for achieving trifecta and functional outcomes. Kaplan-Meier survival analysis (KMA) was used to calculate renal functional outcomes., Results and Limitations: We analyzed 653 patients (mean age 78.4 yr, median follow-up 33 mo; 382 open, 157 laparoscopic, and 114 robotic). Trifecta rate was 40.4% (n=264). Trifecta patients had less transfusion (p<0.001), lower intraoperative (5.3% vs 27%, p<0.001) and postoperative (25.4% vs 37.8%, p=0.001) complications, shorter hospital stay (p=0.045), and lower ΔeGFR (p <0.001). MVA for predictive factors for trifecta revealed decreasing RENAL nephrometry score (odds ratio [OR] 1.26, 95% confidence interval 1.07-1.51, p=0.007) as being associated with increased likelihood to achieve trifecta. Achievement of trifecta was associated with decreased risk of CKD upstaging (OR 0.47, 95% confidence interval 0.32-0.62, p<0.001). KMA showed that trifecta patients had improved 5-yr freedom from CKD stage 3 (93.5% vs 57.7%, p<0.001) and CKD upstaging (84.3% vs 8.2%, p<0.001). Limitations include retrospective design., Conclusions: PN in elderly patients can be performed with acceptable quality outcomes. Trifecta was associated with decreased tumor complexity and improved functional preservation., Patient Summary: We looked at quality outcomes after partial nephrectomy in elderly patients. Acceptable quality outcomes were achieved, measured by a composite outcome called trifecta, whose achievement was associated with improved kidney functional preservation., (Copyright © 2019. Published by Elsevier B.V.)

Background: Cytoreductive nephrectomy (CN) plays an important role in the treatment of a subgroup of metastatic renal cell carcinoma (mRCC) patients., Objective: We aimed to evaluate morbidity associated with this procedure and identify potential predictors thereof to aid patient selection for this procedure and potentially improve patient outcomes., Design, Setting, and Participants: Data from 736 mRCC patients undergoing CN at 14 institutions were retrospectively recorded in the Registry for Metastatic RCC (REMARCC)., Outcome Measurements and Statistical Analysis: Logistic regression analysis was used to identify predictors for intraoperative, any-grade (AGCs), low-grade, and high-grade (HGCs) postoperative complications (according to the Clavien-Dindo classification) as well as 30-d readmission rates., Results and Limitations: Intraoperative complications were observed in 69 patients (10.9%). Thrombectomy (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.08-1.75, p = 0.009) and adjacent organ removal (OR 2.7, 95% CI 1.38-5.30) were significant predictors of intraoperative complications at multivariable analysis. Two hundred seventeen patients (29.5%) encountered AGCs, while 45 (6.1%) encountered an HGC, of whom 10 (1.4%) died. Twenty-four (3.3%) patients had multiple postoperative complications. Estimated blood loss (EBL; OR 1.49, 95% CI 1.08-2.05, p = 0.01) was a significant predictor of AGCs at multivariable analysis. CN case load (OR 0.13, 95% CI 0.03-0.59, p = 0.009) and EBL (OR 2.93, 95% CI 1.20-7.15, p = 0.02) were significant predictors solely for HGCs at multivariable analysis. Forty-one patients (11.5%) were readmitted within 30 d of surgery. No significant predictors were identified. Results were confirmed in a subanalysis focusing solely on patients treated in the contemporary targeted therapy era., Conclusions: Morbidity associated with CN is not negligible. Predictors of high-grade postoperative morbidity are predominantly indicators of complex surgery. EBL is a strong predictor of postoperative complications. CN case load correlates with lower high-grade morbidity and highlights the benefit of centralization of complex surgery. However, risks and benefits should be balanced when considering CN in mRCC patients., Patient Summary: We studied patients with metastatic renal cancer to evaluate the outcomes associated with the surgical removal of the primary kidney tumor. We found that this procedure is often complex and adverse events are not uncommon. High intraoperative blood loss and a small number of cases performed at the treating center are associated with a higher rate of postoperative complications., (Copyright © 2020. Published by Elsevier B.V.)

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

Context: Management of locally recurrent renal cancer is complex., Objective: In this systematic review we analyse the available literature on the management of local renal cancer recurrence., Evidence Acquisition: A systematic search (PubMed, Web of Science, CINAHL, Clinical Trials, and Scopus) of English literature from 2000 to 2017 was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines., Evidence Synthesis: The search identified 1838 articles. Of those, 36 were included in the evidence synthesis. The majority of the studies identified were retrospective and not controlled. Local recurrence after thermal ablation (TA) may be managed with repeat TA. Alternatively, salvage nephrectomy is possible. However, a higher rate of complications should be expected than after primary nephrectomy. Salvage nephrectomy and TA represent treatment options for local recurrence after partial nephrectomy. Local retroperitoneal recurrence after radical nephrectomy is ideally treated with surgical resection, for which minimally invasive approaches might be applicable to select patients. For large recurrences, addition of intraoperative radiation may improve local control. Local tumour destruction appears to be more beneficial than systemic therapy alone for local recurrences., Conclusions: Management of local renal cancer relapse varies according to the clinical course and prior treatments. The available data are mainly limited to noncontrolled retrospective series. After nephron-sparing treatment, TA represents an effective treatment with low morbidity. For local recurrence after radical nephrectomy, the low-level evidence available suggests superiority of surgical excision relative to systemic therapy or best supportive care. As a consequence, surgery should be prioritised when feasible and applicable., Patient Summary: In renal cell cancer, the occurrence and management of local recurrence depend on the initial treatment. This cancer is a disease with a highly variable clinical course. After initial organ-sparing treatment, thermal ablation offers good cancer control and low rates of complications. For recurrence after radical nephrectomy, surgical excision seems to provide the best long-term cancer control and it is superior to medical therapy alone., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

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

Context: Stage migration of organ-confined renal masses is occurring as a result of incidental diagnosis, especially in the elderly. Active surveillance (AS) is gaining clinical traction as a treatment alternative to surgery and focal therapy., Objective: To assess contemporary data and evaluate AS risk trade-offs in the treatment of organ-confined kidney cancer., Evidence Acquisition: A comprehensive search of the Embase, Medline and Cochrane databases was carried out. A systematic review of the role of AS for organ-confined renal masses was performed. A total of 28 studies were included in the systematic review., Evidence Synthesis: The median linear tumor growth rate for clinically localized renal masses (CLRMs) was 0.37cm/yr (interquartile range 0.15-0.7), with 0.22cm/yr in the cT1a subgroup and 0.45cm/yr in the cT1b--2 subgroup. The metastatic progression rate was 1-6% and was similar for cT1a (1-6%) and cT1b (0-5%); other-cause mortality for patients with CLRMs was 0-45% (1-25% for cT1a vs 11-13% for cT1b-2); cancer-specific mortality ranged between 0% and 18%. According to the 2011 Oxford scale, AS as a treatment option for CLRMs remains supported by level 3 evidence., Conclusions: Although no randomized clinical data are available, current data support oncologic safety for AS in the management of CLRMs, particularly for small renal masses and among elderly and/or comorbid patients., Patient Summary: In this review we looked at the outcomes for patients with small kidney masses managed with surveillance. We found that surveillance is a safe initial option for tumors of less than 2cm, especially in elderly and sick patients., (Copyright © 2018 European Association of Urology. All rights reserved.)