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Antonio Franco,1,2 Francesco Ditonno,1,3 Celeste Manfredi,1,4 Andrew D Johnson,1 Avinash Mamgain,1 Oren Feldman-Schultz,1 Carol L Feng,1 Antony A Pellegrino,5,6 Maria Carmen Mir,7 Francesco Porpiglia,8 Simone Crivellaro,5 Cosimo De Nunzio,2 Alexander K Chow,1 Riccardo Autorino1 1Department of Urology, Rush University, Chicago, IL, USA; 2Department of Urology, Sant’Andrea Hospital, Sapienza University, Rome, Italy; 3Department of Urology, University of Verona, Verona, Italy; 4Urology Unit, “Luigi Vanvitelli” University, Naples, Italy; 5Department of Urology, University of Illinois at Chicago, Chicago, Illinois, USA; 6Unit of Urology/Division of Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy; 7Department of Urology, Hospital Universitario La Ribera, Valencia, Spain; 8Department of Oncology, Division of Urology, University of Turin, San Luigi Gonzaga Hospital, Orbassano, ItalyCorrespondence: Riccardo Autorino, Professor of Urology, Director of Surgical Innovation & Clinical Research, Department of Urology, Rush University Medical Center, 1725 W Harrison St Professional Building – Suite 970, Chicago, IL, 60612, USA, Email ricautor@gmail.com; Riccardo_autorino@rush.eduAbstract: Robot-assisted surgery has emerged as a transformative technology, revolutionizing surgical approaches and techniques that decades ago could barely be imagined. The field of urology has taken charge in pioneering a new era of minimally invasive surgery with the ascent of robotic systems which offer enhanced visualization, precision, dexterity, and enabling surgeons to perform intricate maneuvers with improved accuracy. This has led to improved surgical outcomes, including reduced blood loss, lower complication rates, and faster patient recovery. The aim of our review is to present an evidence-based critical analysis on the most pioneering robotic urologic approaches described over the last eight years (2015– 2023).Keywords: robotic urologic surgery, robot-assisted, minimally invasive, image-guided surgery, single port robot

Maria C Mir,1 Binoy Joseph,1 Rona Zhao,1 Damien M Bolton,1 Dennis Gyomber,1 Nathan Lawrentschuk1,21University of Melbourne, Department of Surgery, Austin Hospital, Melbourne, VIC, Australia; 2Ludwig Institute for Cancer Research, Austin Hospital, Melbourne, VIC, AustraliaObjectives: Our objectives were to analyze the effectiveness of epidural anesthesia in patients who underwent open retropubic radical prostatectomy (RRP) at our institution over the past decade, and to examine subsequent oncologic outcomes, comparing those receiving with those not receiving epidural anesthesia.Methods: A comprehensive database of all patients undergoing RRP from November 1996 to December 2006 was analyzed; 354 patients underwent RRP at our institution and were divided into those receiving or not receiving an epidural. An independent pain management team scoring technical success found epidural technique to be consistent. Oncological outcome was an endpoint of our study, comparing both analysis groups. We classed prostate-specific antigen (PSA) recurrence after RRP as a serum PSA ≥ 0.2 ng/mL at any stage of postoperative follow-up. Complications were recorded to 30 days using the modified Clavien system, and full statistical analyses were undertaken.Results: Records were available for 239 men; we observed a decreased trend in the use of epidural for pain management, along with a decrease in average hospital stay and an overall epidural success rate of 64%. When dividing data into RRP with and without epidural, we found a median hospital stay of 7 days for patients receiving an epidural compared with 6 days for those not receiving an epidural. The differences were statistically significant (P < 0.048) and remained so after adjusting for complications (P < 0.0001). Regarding oncological outcome, PSA recurrence was further analyzed in this cohort. Percentage of recurrence was higher (14.8%) for patients receiving an epidural than for the non-epidural group (4.8%). The differences were statistically significant (P = 0.012).Conclusion: Epidural analgesia increased length of hospital stay and technical problems related to the epidural. Furthermore, men receiving an epidural showed an increased recurrence of PSA. In light of our findings, epidurals are probably not indicated for men undergoing RRP. However, as minimally invasive techniques are becoming more widespread, and epidural analgesia is being used less frequently, large randomized controlled trials to definitively support our hypotheses are unlikely to be undertaken.Keywords: prostate neoplasm, surgery, prostatectomy, analgesia, epidural

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.)

Objective: To investigate the influence of statins on the survival outcomes of patients with non-muscle-invasive bladder cancer (NMIBC) treated with adjuvant intravesical bacille Calmette-Guérin (BCG) immunotherapy., Patients and Methods: A retrospective cohort of consecutive patients with NMIBC who received intravesical BCG therapy from 2001 to 2020 and statins prescription were identified. Overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and progression-free survival (PFS) were analysed between the Statins Group vs No-Statins Group using Kaplan-Meier method and multivariable Cox regression., Results: A total of 2602 patients with NMIBC who received intravesical BCG were identified. The median follow-up was 11.0 years. On Kaplan-Meier analysis, the Statins Group had significant better OS (P < 0.001), CSS (P < 0.001), and PFS (P < 0.001). Subgroup analysis indicated statins treatment started before BCG treatment had better CSS (P = 0.02) and PFS (P < 0.01). Upon multivariable Cox regression analysis, the 'statins before BCG' group was an independent protective factor for OS (hazard ratio [HR] 0.607, 95% confidence interval [CI] 0.514-0.716), and CSS (HR 0.571, 95% CI 0.376-0.868), but not RFS (HR 0.885, 95% CI 0.736-1.065), and PFS (HR 0.689, 95% CI 0.469-1.013)., Conclusions: Statins treatment appears to offer protective effects on OS and CSS for patients with NMIBC receiving adjuvant intravesical BCG., (© 2024 BJU International.)

Purpose: To evaluate the incidence of postoperative complications after cytoreductive nephrectomy (CN) following first-line treatment for metastatic renal cell carcinoma (mRCC), and to compare it with postoperative complications of upfront CN., Methods: For this population-based retrospective study, the PearlDiver Mariner database (PearlDiver Technologies, Colorado Springs, CO), a database of insurance billing records was analyzed. Using relevant ICD-9/10 and CPT codes, patients diagnosed with mRCC between 2011 and 2021, who received first-line systemic molecular therapy (SMT), either tyrosine kinase inhibitors (TKI) or immune-checkpoint inhibitors (ICI), were identified. The selected population was stratified into two cohorts according to the timing of CN (deferred: after SMT vs. upfront: before SMT). Propensity-score matching (PSM) was performed as per baseline patients' characteristics to control for potential confounders between the two cohorts. The primary outcome was to compare 30-day postoperative complications rate between patients undergoing upfront vs. deferred CN., Results: After PSM, 162 patients who received upfront CN were compared with 162 patients who underwent deferred CN. The overall rate of 30-day postoperative complications was statistically significantly higher in patients undergoing deferred CN (33.9%), compared to patients treated with upfront CN (21%, p < 0.01). In addition, the rate of both medical (26.5% vs. 14.2%, p < 0.01) and surgical (14.8 vs. 7.4%, p = 0.03) complication rate was statistically significantly higher in deferred vs. upfront CN. Multivariable logistic regression analysis revealed that none of the treatment regimens significantly predicted the occurrence of postoperative complications., Conclusion: Patients undergoing deferred CN experience a higher rates of overall, medical, and surgical 30-day postoperative complications compared to those receiving upfront surgery. Findings from this study should be interpreted within the limitations of this type of analysis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Prognostic tools in pathological-node (pN) patients after radical cystectomy (RC) are needed., Objectives: To evaluate the prognostic impact of lymph node (LN)-density on disease-specific survival (DSS) in patients with bladder cancer (BC) undergoing RC with pelvic lymph node dissection., Methods: We analyzed a multi-institutional cohort of 1169 patients treated with upfront RC for cT1-4aN0M0 urothelial BCat nine centers. LN-densitywas calculated as the ratio of the number of positive LNs×100% to the number of LNs removed. The optimal LN-density cut-off value was defined by creating a time-dependent receiver operating characteristic (ROC) curve in pN patients. Univariable and multivariable Cox' regression analyses were used to assess the effect of conventional Tumor Nodes Metastasis (TNM) nodal staging system, LN-density and other LN-related variables on DSS in the pN-positive cohort., Results: Of the 1169 patients, 463 (39.6%) patients had LN-involvement. The area under the ROC curve was 0.60 and the cut-off for LN-density was set at 20%, 223 of the pN-positive patients (48.2%) had a LN-density ≥ 20%. In multivariable models, the number of LN-metastases (HR 1.03, p = 0.005) and LN-density, either as continuous (HR 1.01, p = 0.013) or as categorical variable (HR 1.37, p = 0.014), were independently associated with worse DSS, whereas pN-stage was not., Conclusions: LN-density ≥ 20% was an independent predictor of worse DSS in BC patients with LN-involvement at RC. The integration of LN-density and other LN-parameters rather than only conventional pN-stage may contribute to a more refined risk-stratification in BC patients with nodal involvement., Competing Interests: BWGvR, SFS, ARZ, AH, TCMZ and YL are Editorial Board Members of this journal but were blinded and not involved in the peer-review process nor had access to any information regarding its peer-review. Peter J. Bostrom: Peter Bostrom reports research grant from Juselius Foundation and Cancer Foundation Finland. Additionally, consultation fees from Astellas and Janssen are reported. Shahrokh. F. Shariat: S.F. Shariat reports advisory board of/and or speaker for Astellas, Astra Zeneca, Bayer, BMS, Cepheid, Ferring, Ipsen, Janssen, Lissy, MSD, Olympus, Pfizer, Pierre Fabre, Roche, Sanochemia and Sanofi. Joost L. Boormans: JL Boormans received travel grants from Combat medical to attend scientific meetings and has received honoraria by MSD, Roche, BMS and Janssen Pharmaceuticals for consultancy work. Yair Lotan: Y Lotan reported consultancy for Nanorobotics, C2I genomics, Photocure, Astra-Zeneca, Merck, Fergene, Abbvie, Nucleix, Ambu, Seattle Genetics, Hitachi, Ferring Research, verity pharmaceutics, virtuoso surgical, Stimit, Urogen, Vessi medical, CAPs medical, Xcures, BMS, Nonagen, Aura Biosciences, Inc., Convergent Genomics, Pacific Edge, Pfizer, Phinomics Inc, CG oncology, Uroviu, On target lab. Bas WG van Rhijn: BWG van Rhijn reported Advisory board meetings: QED Therapeutics and Incyte International Biosciences. The remaining authors reported no further conflicts of interest., (© 2024 – The authors. Published by IOS Press.)

Background: Positron Emission Tomography-Computed Tomography using Prostate-Specific Membrane Antigen (PSMA PET/CT) is notable for its superior sensitivity and specificity in detecting recurrent PCa and is under investigation for its potential in pre-treatment staging. Despite its established efficacy in nodal and metastasis staging in trial setting, its role in primary staging awaits fuller validation due to limited evidence on oncologic outcomes. This systematic review and meta-analysis aims to appraise the diagnostic accuracy of PSMA PET/CT compared to CI for comprehensive PCa staging., Methods: Medline, Scopus and Web of science databases were searched till March 2023. Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed to identify eligible studies. Primary outcomes were specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of PSMA PET/CT for local, nodal and metastatic staging in PCa patients. Due to the unavailability of data, a meta-analysis was feasible only for detection of seminal vesicles invasion (SVI) and LNI., Results: A total of 49 studies, comprising 3876 patients, were included. Of these, 6 investigated accuracy of PSMA PET/CT in detection of SVI. Pooled sensitivity, specificity, PPV and NPV were 42.29% (95%CI: 29.85-55.78%), 87.59% (95%CI: 77.10%-93.67%), 93.39% (95%CI: 74.95%-98.52%) and 86.60% (95%CI: 58.83%-96.69%), respectively. Heterogeneity analysis revealed significant variability for PPV and NPV. 18 studies investigated PSMA PET/CT accuracy in detection of LNI. Aggregate sensitivity, specificity, PPV and NPV were 43.63% (95%CI: 34.19-53.56%), 85.55% (95%CI: 75.95%-91.74%), 67.47% (95%CI: 52.42%-79.6%) and 83.61% (95%CI: 79.19%-87.24%). No significant heterogeneity was found between studies., Conclusions: The present systematic review and meta-analysis highlights PSMA PET-CT effectiveness in detecting SVI and its good accuracy in LNI compared to CI. Nonetheless, it also reveals a lack of high-quality research on its performance in clinical T staging, extraprostatic extension and distant metastasis evaluation, emphasizing the need for further rigorous studies., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background and Aim: The role of histomorphological subtyping is an issue of debate in papillary renal cell carcinoma (papRCC). This multi-institutional study investigated the prognostic role of histomorphological subtyping in patients undergoing curative surgery for nonmetastatic papRCC., Patients and Methods: A total of 1,086 patients undergoing curative surgery were included from a retrospectively collected multi-institutional nonmetastatic papRCC database. The patients were divided into 2 groups based on histomorphological subtyping (type 1, n = 669 and type 2, n = 417). Furthermore, a propensity score-matching (PSM) cohort in 1:1 ratio (n = 317 for each subtype) was created to reduce the effect of potential confounding variables. The primary outcome of the study, the predictive role of histomorphological subtyping on the prognosis (recurrence free survival [RFS], cancer specific survival [CSS] and overall survival [OS]) in nonmetastatic papRCC after curative surgery, was investigated in both overall and PSM cohorts., Results: In overall cohort, type 2 group were older (66 vs. 63 years, P = 0.015) and more frequently underwent radical nephrectomy (37.4% vs. 25.6%, P < 0.001) and lymphadenectomy (22.3% vs. 15.1%, P = 0.003). Tumor size (4.5 vs. 3.8 cm, P < 0.001) was greater, and nuclear grade (P < 0.001), pT stage (P < 0.001), pN stage (P < 0.001), VENUSS score (P < 0.001) and VENUSS high risk (P < 0.001) were significantly higher in type 2 group. 5-year RFS (89.6% vs. 74.2%, P < 0.001), CSS (93.9% vs. 84.2%, P < 0.001) and OS (88.5% vs. 78.5%, P < 0.001) were significantly lower in type 2 group. On multivariable analyses, type 2 was a significant predictor for RFS (HR:1.86 [95%CI:1.33-2.61], P < 0.001) and CSS (HR:1.91 [95%CI:1.20-3.04], P = 0.006), but not for OS (HR:1.27 [95%CI:0.92-1.76], P = 0.150). In PSM cohort balanced with age, gender, symptoms at diagnosis, pT and pN stages, tumor grade, surgical margin status, sarcomatoid features, rhabdoid features, and presence of necrosis, type 2 increased recurrence risk (HR:1.75 [95%CI: 1.16-2.65]; P = 0.008), but not cancer specific mortality (HR: 1.57 [95%CI: 0.91-2.68]; P = 0.102) and overall mortality (HR: 1.01 [95%CI: 0.68-1.48]; P = 0.981) CONCLUSIONS: This multiinstitutional study suggested that type 2 was associated with adverse histopathologic outcomes, and predictor of RFS and CSS after surgical treatment of nonmetastatic papRCC, in overall cohort. In propensity score-matching cohort, type 2 remained the predictor of RFS. Eventhough 5th WHO classification for renal tumors eliminated histomorphological subtyping, these findings suggest that subtyping is relevant from the point of prognostic view., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. 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.)

Renal cell carcinoma (RCC) incidence has doubled over the past few decades. However, death rates have remained stable as the number of incidental renal mass diagnoses peaked. RCC has been recognized as a European health care issue, but to date, no screening programmes have been introduced. Well-known modifiable risk factors for RCC are smoking, obesity and hypertension. A direct association between cigarette consumption and increased RCC incidence and RCC-related death has been reported, but the underlying mechanistic pathways for this association are still unclear. Obesity is associated with an increased risk of RCC, but interestingly, improved survival outcomes have been reported in obese patients, a phenomenon known as the obesity paradox. Data on the association between other modifiable risk factors such as diet, dyslipidaemia and physical activity with RCC incidence are conflicting, and potential mechanisms underlying these associations remain to be elucidated., (© 2023. Springer Nature Limited.)

Introduction: Cisplatin-based neoadjuvant chemotherapy (NAC) is the standard of care for patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC). Cisplatin, however, can induce renal toxicity. Furthermore, RC is an independent risk factor for renal injury, with decreases in estimated glomerular filtration rate (eGFR) of up to 6 mL/min/1.73 m 2 reported at one year postoperatively. Our objective was to evaluate the effect of cisplatin-based NAC and RC on the renal function of patients undergoing both., Methods: We analyzed a multicenter database of patients with MIBC, all of whom received cisplatin-based NAC prior to RC. eGFR values were collected at time points T1 (before NAC), T2 (after NAC but before RC), and T3 (one year post-RC). eGFR and proportion of patients with eGFR <60 ml/min/1.73m 2 (chronic kidney disease [CKD] stage ≥3) were compared between these time points. As all patients in this dataset had received NAC, we identified a retrospective cohort of patients from one institution who had undergone RC during the same time period without NAC for context., Results: We identified 234 patients with available renal function data. From T1 to T3, there was a mean decline in eGFR of 17% (13 mL/min/1.73 m 2 ) in the NAC cohort and an increase in proportion of patients with stage ≥3 CKD from 27% to 50%. The parallel cohort of patients who did not receive NAC was comprised of 236 patients. The mean baseline eGFR in this cohort was lower than in the NAC cohort (66 vs. 75 mL/min/1.73 m 2 ). The mean eGFR decline in this non-NAC cohort from T1 to T3 was 6% (4 mL/min/1.73 m 2 ), and the proportion of those with stage ≥3 CKD increased from 37% to 51%., Conclusions: Administration of NAC prior to RC was associated with a 17% decline in eGFR and a nearly doubled incidence of stage ≥3 CKD at one year after RC. Patients who underwent RC without NAC had a higher rate of stage ≥3 CKD at baseline but appeared to have less renal function loss at one year.

Background and Objective: Radical nephroureterectomy (RNU) represents the gold standard treatment for non-metastatic upper tract urothelial cancer. We sought to provide a comprehensive review of reported oncologic outcomes of the RNU procedure and of factors that might impact these outcomes., Methods: A non-systematic review of the literature was conducted by performing an electronic literature search using PubMed with "radical nephroureterectomy" and "oncologic outcomes" as free text search terms. Both original articles and systematic reviews were considered. Search was limited to articles in English that were published in the last 20 years., Key Content and Findings: Open and laparoscopic RNU offer comparable oncologic outcomes. In more recent years, the discussion has de facto shifted towards the "oncological safety" of robotic RNU, which also seems to offer comparable oncologic outcomes. Several studies have looked at the impact of different treatment-, patient- and tumor-related factors. Among treatment-related factors, attention has been given to diagnostic ureteroscopy and the risk of intravesical recurrence. Surgical wait time and perioperative blood transfusion have also been studied. Perioperative chemotherapy, specifically adjuvant therapy, was shown to improve survival. Among patient-related factors, baseline chronic kidney disease, diabetes mellitus, body mass index, and systemic inflammation have gained recent attention. Some tumor related factors, such as stage, grade, location, and multifocality may negatively impact survival outcomes. Lymphovascular invasion and histologic variants are clinically significant pathological findings., Conclusions: RNU is a procedure with measured long-term oncologic outcomes. Minimally invasive techniques have gained an established role as they seem to offer comparable oncologic "safety", although special attention is needed in relation to the method of bladder cuff excision. Robotic RNU is gaining popularity, and while evidence remains limited, the current literature supports the oncologic safety of this procedure. Several factors, which can be categorized as treatment-related, patient-related, and tumor-related, might impact the oncologic outcomes of UTUC patients undergoing RNU. These factors can provide crucial information to stratify patients based on their relative risk of disease recurrence and mortality which may guide clinical decision-making., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-22-882/coif). The series “Upper Tract Urothelial Cancer” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2023 Translational Andrology and Urology. All rights reserved.)

Urothelial carcinoma (UC), the sixth most common cancer in Western countries, includes upper tract urothelial carcinoma (UTUC) and bladder carcinoma (BC) as the most common cancers among UCs (90-95%). BC is the most common cancer and can be a highly heterogeneous disease, including both non-muscle-invasive (NMIBC) and muscle-invasive (MIBC) forms with different oncologic outcomes. Approximately 80% of new BC diagnoses are classified as NMIBC after the initial transurethral resection of the bladder tumor (TURBt). In this setting, intravesical instillation of Bacillus Calmette-Guerin (BCG) is the current standard treatment for intermediate- and high-risk patients. Unfortunately, recurrence occurs in 30% to 40% of patients despite adequate BCG treatment. Radical cystectomy (RC) is currently considered the standard treatment for NMIBC that does not respond to BCG. However, RC is a complex surgical procedure with a recognized high perioperative morbidity that is dependent on the patient, disease behaviors, and surgical factors and is associated with a significant impact on quality of life. Therefore, there is an unmet clinical need for alternative bladder-preserving treatments for patients who desire a bladder-sparing approach or are too frail for major surgery. In this review, we aim to present the strategies in BCG-unresponsive NMIBC, focusing on novel molecular therapeutic targets.

Objectives: To evaluate variant histologies (VHs) for disease-specific survival (DSS) in patients with invasive urothelial bladder cancer (BCa) undergoing radical cystectomy (RC)., Materials and Methods: We analysed a multi-institutional cohort of 1082 patients treated with upfront RC for cT1-4aN0M0 urothelial BCa at eight centres. Univariable and multivariable Cox' regression analyses were used to assess the effect of different VHs on DSS in overall cohort and three stage-based analyses. The stages were defined as 'organ-confined' (≤pT2N0), 'locally advanced' (pT3-4N0) and 'node-positive' (pTanyN1-3)., Results: Overall, 784 patients (72.5%) had pure urothelial carcinoma (UC), while the remaining 298 (27.5%) harboured a VH. Squamous differentiation was the most common VH, observed in 166 patients (15.3%), followed by micropapillary (40 patients [3.7%]), sarcomatoid (29 patients [2.7%]), glandular (18 patients [1.7%]), lymphoepithelioma-like (14 patients [1.3%]), small-cell (13 patients [1.2%]), clear-cell (eight patients [0.7%]), nested (seven patients [0.6%]) and plasmacytoid VH (three patients [0.3%]). The median follow-up was 2.3 years. Overall, 534 (49.4%) disease-related deaths occurred. In uni- and multivariable analyses, plasmacytoid and small-cell VHs were associated with worse DSS in the overall cohort (both P = 0.04). In univariable analyses, sarcomatoid VH was significantly associated with worse DSS, while lymphoepithelioma-like VH had favourable DSS compared to pure UC. Clear-cell (P = 0.015) and small-cell (P = 0.011) VH were associated with worse DSS in the organ-confined and node-positive cohorts, respectively., Conclusions: More than 25% of patients harboured a VH at time of RC. Compared to pure UC, clear-cell, plasmacytoid, small-cell and sarcomatoid VHs were associated with worse DSS, while lymphoepithelioma-like VH was characterized by a DSS benefit. Accurate pathological diagnosis of VHs may ensure tailored counselling to identify patients who require more intensive management., (© 2023 BJU International.)

Background and Objectives : To date, sparse evidence exists about the impact of inflammatory serum markers in predicting perioperative complications after radical cystectomy (RC) for bladder cancer (BC). Here, we evaluated the role of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), C-reactive protein (CRP), and plasma fibrinogen in predicting perioperative morbidity and unplanned 30-days readmission after RC for BC. Materials and methods : We relied on a collaborative database of 271 patients who underwent open RC for cT1-4a N0 M0 BC between January 2012 and December 2022. Univariable and multivariable binomial logistic regression analyses were performed to assess the odds ratio (OR) with 95% confidence intervals (CI) testing the ability of each serum marker to predict postoperative complications (any-grade and major complications), and 30-days unplanned readmission. Results : The median age at RC was 73 yr (IQR 67-79). A total of 182 (67.2%) patients were male and the median BMI was 25.2 (IQR 23.2-28.4). Overall, 172 (63.5%) patients had a Charlson Comorbidity Index (CCI) greater than 2 points and 98 (36.2%) were current smokers at the time of RC. Overall, 233 (86.0%) patients experienced at least one complication after RC. Of these, 171 (63.1%) patients had minor complications (Clavien-Dindo grade 1-2) while 100 (36.9%) experienced major complications (Clavien-Dindo grade ≥ 3). According to multivariable analysis, current smoking status, high plasma fibrinogen, and preoperative anemia were independently associated with major complications (OR 2.10, 95%CI 1.15-4.90, p = 0.02), (OR 1.51, 95%CI 1.26-1.98, p = 0.09), and (OR 1.35, 95%CI 1.17-2.57, p = 0.03), respectively. Overall, 56 (20.7%) patients experienced a 30-days unplanned readmission. According to univariable analysis, high preoperative CRP and hyperfibrinogenemia were significantly associated with an increased risk of unplanned readmission (OR 2.15, 95%CI 1.15-4.16, p = 0.02; OR 2.18, 95%CI 1.13-4.44, p = 0.02, respectively). Conclusions : In our study, the preoperative immune-inflammation signature described by NLR, PLR, LMR, SII, and CRP showed a low reliability in predicting perioperative course after RC. Preoperative anemia and hyperfibrinogenemia were independent predictors of major complications. Further studies are pending in order to draw definitive conclusions.

Purpose: Half of patients with muscle-invasive bladder cancer worldwide may not receive curative-intent therapy. Elderly or frail patients are most affected by this unmet need. TAR-200 is a novel, intravesical drug delivery system that provides sustained, local release of gemcitabine into the bladder over a 21-day dosing cycle. The phase 1 TAR-200-103 study evaluated the safety, tolerability, and preliminary efficacy of TAR-200 in patients with muscle-invasive bladder cancer who either refused or were unfit for curative-intent therapy., Materials and Methods: Eligible patients had cT2-cT3bN0M0 urothelial carcinoma of the bladder. TAR-200 was inserted for 4 consecutive 21-day cycles over 84 days. The primary end points were safety and tolerability at 84 days. Secondary end points included rates of clinical complete response and partial response as determined by cystoscopy, biopsy, and imaging; duration of response; and overall survival., Results: Median age of the 35 enrolled patients was 84 years, and most were male (24/35, 68.6%). Treatment-emergent adverse events related to TAR-200 occurred in 15 patients. Two patients experienced treatment-emergent adverse events leading to removal of TAR-200. At 3 months, complete response and partial response rates were 31.4% (11/35) and 8.6% (3/35), respectively, yielding an overall response rate of 40.0% (14/35; 95% CI 23.9-57.9). Median overall survival and duration of response were 27.3 months (95% CI 10.1-not estimable) and 14 months (95% CI 10.6-22.7), respectively. Progression-free rate at 12 months was 70.5%., Conclusions: TAR-200 was generally safe, well tolerated, and had beneficial preliminary efficacy in this elderly and frail cohort with limited treatment options.

Purpose: While the presence of residual disease at the time of radical cystectomy for bladder cancer is an established prognostic indicator, controversy remains regarding the importance of maximal transurethral resection prior to neoadjuvant chemotherapy. We characterized the influence of maximal transurethral resection on pathological and survival outcomes using a large, multi-institutional cohort., Materials and Methods: We identified 785 patients from a multi-institutional cohort undergoing radical cystectomy for muscle-invasive bladder cancer after neoadjuvant chemotherapy. We employed bivariate comparisons and stratified multivariable models to quantify the effect of maximal transurethral resection on pathological findings at cystectomy and survival., Results: Of 785 patients, 579 (74%) underwent maximal transurethral resection. Incomplete transurethral resection was more frequent in patients with more advanced clinical tumor (cT) and nodal (cN) stage ( P < .001 and P < .01, respectively), with more advanced ypT stage at cystectomy and higher rates of positive surgical margins ( P < .01 and P < .05, respectively). In multivariable models, maximal transurethral resection was associated with downstaging at cystectomy (adjusted odds ratio 1.6, 95% CI 1.1-2.5). In Cox proportional hazards analysis, maximal transurethral resection was not associated with overall survival (adjusted HR 0.8, 95% CI 0.6-1.1)., Conclusions: In patients undergoing transurethral resection for muscle-invasive bladder cancer prior to neoadjuvant chemotherapy, maximal resection may improve pathological response at cystectomy. However, the ultimate effects on long-term survival and oncologic outcomes warrant further investigation.

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.)

Purpose: We hypothesized that two-tier re-classification of the "M" (metastasis) domain of the Tumor-Node-Metastasis (TNM) staging of Renal Cell Carcinoma (RCC) may improve staging accuracy than the current monolithic classification, as advancements in the understanding of tumor biology have led to increased recognition of the heterogeneous potential of metastatic RCC (mRCC)., Methods: Multicenter retrospective analysis of patients from the REMARCC (REgistry of MetAstatic RCC) database. Patients were stratified by number of metastases into two groups, M1 (≤3, "Oligometastatic") and M2 (>3, "Polymetastatic"). Primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival (CSS). Cox-regression and Kaplan-Meier (KMA) analysis were utilized for outcomes, and receiver operating characteristic analysis (ROC) was utilized to assess diagnostic accuracy compared to current "M" staging., Results: 429 patients were stratified into proposed M1 and M2 groups (M1 = 286/M2 = 143; median follow-up 19.2 months). Cox-regression revealed M2 classification as an independent risk factor for worsened all-cause mortality (HR=1.67, p=0.001) and cancer-specific mortality (HR=1.74, p<0.001). Comparing M1-oligometastatic vs. M2-polymetastatic groups, KMA revealed significantly higher 5-year OS (36% vs. 21%, p<0.001) and 5-year CSS (39% vs. 17%, p<0.001). ROC analyses comparing OS and CSS, for M1/M2 reclassification versus unitary M designation currently in use demonstrated improved c-index for OS (M1/M2 0.635 vs. unitary M 0.500) and CSS (M1/M2 0.627 vs. unitary M 0.500)., Conclusion: Subclassification of Stage "M" domain of mRCC into two clinical substage categories based on metastatic burden corresponds to distinctive tumor groups whose oncological potential varies significantly and result in improved predictive capability compared to current staging., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Meagher, Mir, Minervini, Kriegmair, Heck, Porpiglia, Van Bruwaene, Linares, Hevia, D’Anna, Veccia, Roussel, Claps, Palumbo, Marchioni, Afari, Saitta, Liu, Rubio, Campi, Mari, Amiel, Checcucci, Musquera, Guruli, Pavan, Albersen, Antonelli, Klatte, Autorino, McKay and Derweesh.)

Objective: To externally validate Yonsei nomogram., Methods: From 2000 through 2018, 3526 consecutive patients underwent on-clamp PN for cT1 renal masses at 23 centers were included. All patients had two kidneys, preoperative eGFR ≥60 ml/min/1.73 m2, and a minimum follow-up of 12 months. New-onset CKD was defined as upgrading from CKD stage I or II into CKD stage ≥III. We obtained the CKD-free progression probabilities at 1, 3, 5, and 10 years for all patients by applying the nomogram found at https://eservices.ksmc.med.sa/ckd/. Thereafter, external validation of Yonsei nomogram for estimating new-onset CKD stage ≥III was assessed by calibration and discrimination analysis., Results and Limitation: Median values of patients' age, tumor size, eGFR and follow-up period were 47 years (IQR: 47-62), 3.3 cm (IQR: 2.5-4.2), 90.5 ml/min/1.73 m2 (IQR: 82.8-98), and 47 months (IQR: 27-65), respectively. A total of 683 patients (19.4%) developed new-onset CKD. The 5-year CKD-free progression rate was 77.9%. Yonsei nomogram demonstrated an AUC of 0.69, 0.72, 0.77, and 0.78 for the prediction of CKD stage ≥III at 1, 3, 5, and 10 years, respectively. The calibration plots at 1, 3, 5, and 10 years showed that the model was well calibrated with calibration slope values of 0.77, 0.83, 0.76, and 0.75, respectively. Retrospective database collection is a limitation of our study., Conclusions: The largest external validation of Yonsei nomogram showed good calibration properties. The nomogram can provide an accurate estimate of the individual risk of CKD-free progression on long-term follow-up., (© 2022 The Japanese Urological Association.)

Introduction: After transplantation, approximately 10% of renal cell carcinomas are detected in graft kidneys. These tumors (gRCC) present surgeons with the difficulty of finding a treatment that guarantees both oncological clearance and maintenance of function. We conducted a systematic review and an individual patient data meta-analysis on the oncology, safety and functional outcomes of the available treatments for gRCC., Evidence Acquisition: A systematic search was performed across MEDLINE, EMBASE, and Web of Science including any study reporting perioperative, functional and survival outcomes for patients undergoing graft nephrectomy (GN), partial nephrectomy (PN) or thermal ablation (TA) for gRCC. Quade's ANCOVA, Spearman Rho and Pearson χ 2 , Kaplan-Meier, Log-rank and Standard Cox regression and other tests were used to compare treatments. Studies' quality was evaluated using a modified version of Newcastle Ottawa Scale., Evidence Synthesis: A number of 29 studies (357 patients) were included. No differences between TA and PN were found in terms of safety, functional and oncological outcomes for T1a gRCCs. When applied to pT1b gRCC, PN showed no difference in complications, progression or cancer-specific deaths compared to smaller lesions; PN validity for pT2 gRCCs should be considered unverified due to lack of sufficient evidence. The efficacy and safety of PN or TA for multiple gRCC remain controversial. In case of non-functioning, large (T≥2), complicated or metastatic gRCCs, GN appears to be the most reasonable choice. Quality of evidence ranged from very low to moderate. Studies with large cohorts and longer follow-up are still needed to clarify oncological and functional differences., Conclusions: PN and TA might be offered as a nephron-sparing treatment in patients with T1a gRCC. There is no significant difference between these options and GN in terms of oncological outcomes and complications. PN and TA offer similar functional outcomes and graft preservation. PN for T1b gRCC seems feasible and safe, but its validity should be considered unverified.

Introduction and Objectives: To evaluate the impact of the Controlling Nutritional Status (CONUT) score on perioperative morbidity and oncological outcomes of bladder cancer (BC) patients treated with radical cystectomy (RC)., Materials and Methods: We retrospectively analyzed a multi-institutional cohort of 347 patients treated with RC for clinical-localized BC between 2005 and 2019. The CONUT-score was defined as an algorithm including serum albumin, total lymphocyte count, and cholesterol. Multivariable logistic regression analyses were performed to evaluate the ability of the CONUT-score to predict any-grade complications, major complications and 30 days readmission. Multivariable Cox' regression models were performed to evaluate the prognostic effect of the CONUT-score on recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS)., Results: A cut-off value to discriminate between low and high CONUT-score was determined by calculating the receiver operating characteristic (ROC) curve. The area under the curve was 0.72 hence high CONUT-score was defined as ≥3 points. Overall, 112 (32.3%) patients had a high CONUT. At multivariable logistic regression analyses, high CONUT was associated with any-grade complications (OR 3.58, P = 0.001), major complications (OR 2.56, P = 0.003) and 30 days readmission (OR 2.39, P = 0.01). On multivariable Cox' regression analyses, high CONUT remained associated with worse RFS (HR 2.57, P < 0.001), OS (HR 2.37, P < 0.001) and CSS (HR 3.52, P < 0.001)., Conclusions: Poor nutritional status measured by the CONUT-score is independently associated with a poorer postoperative course after RC and is predictive of worse RFS, OS, and CSS. This simple index could serve as a comprehensive personalized risk-stratification tool identifying patients who may benefit from an intensified regimen of supportive cares., (Copyright © 2022 Elsevier Inc. 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.)

Purpose of Review: In patients with muscle invasive bladder cancer (MIBC) or unresectable non-MIBC, radical cystectomy is routinely combined with bilateral pelvic lymph node dissection (LND) owing to the oncological benefits found in recurrence-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS) compared with radical cystectomy alone. However, the optimal anatomic extent of LND is still unclear., Recent Findings: Retrospective studies were consistent in reporting oncological benefits of extended LND over nonextended LND. A recent RCT (the LEA trial) failed to demonstrate any benefit in terms of RFS, CSS and OS of super-extended LND over standard LND. Several confounding factors hindered the interpretation of the results, leaving the question of the right extent for LND still open. Results of a similar study, the SWOG S1011 are, therefore, highly anticipated. This study differed from the LEA study in several aspects but might also turn out to be a negative study., Summary: There are still no firm data on the oncological benefit brought by more extended LND in patients with MIBC. Survival benefits seem limited, at least in the general population. Other factors could influence the impact of LND on survival, including the administration of adjuvant and neoadjuvant chemotherapies., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

With greater awareness of indolence underlying small renal masses (SRM ≤ 4 cm) and the morbidity of invasive treatment, active surveillance for SRM patients is being increasingly utilized on an international level. This synopsis summarizes the 2022 review and expert opinion recommendations provided to the International Consultation of Urological Diseases (ICUD) by 10 urologists from high-volume active surveillance practices at international centers. Topics reviewed include SRM biology and clinical behavior, current national and international guidelines for active surveillance of SRM patients, active surveillance utilization patterns and barriers to implementation, outcomes and limitations of the active surveillance literature, criteria for active surveillance patient selection, protocols for active surveillance management including frequency/modality of imaging and the role of renal tumor biopsy, triggers for delayed intervention during active surveillance including tumor factors and patient factors, and pathological outcomes of delayed intervention. We conclude that despite limitations of the current literature, active surveillance is a safe initial management strategy for many SRM patients. The slow growth and low metastatic potential of SRMs, combined with no evidence to suggest oncologic compromise with delay to treatment, should provide confidence to both patients and providers who are considering active surveillance. Future research for prioritization should include characterization of long-term active surveillance outcomes including rates of metastasis and delayed intervention, standardization of objective tumor progression criteria for triggering delayed intervention, and further delineation of the role for active surveillance in young and healthy patients., Competing Interests: Competing Interests None declared.

Purpose: Cisplatin-based chemotherapy followed by radical cystectomy (RC) is recommended in patients with muscle-invasive bladder cancer (MIBC). However, up to 50% of patients are cisplatin ineligible. The aim of this study was to compare clinical outcomes after ≥ 3 cycles of preoperative gemcitabine-carboplatin (gem-carbo) versus gemcitabine-cisplatin (gem-cis)., Methods: We identified 1865 patients treated at 19 centers between 2000 and 2013. Patients were included if they had received ≥ 3 cycles of neoadjuvant (cT2-4aN0M0) or induction (cTanyN + M0) gem-carbo or gem-cis followed by RC., Results: We included 747 patients treated with gem-carbo (n = 147) or gem-cis (n = 600). Patients treated with gem-carbo had a higher Charlson Comorbidity Index (p = 0.016) and more clinically node-positive disease (32% versus 20%; p = 0.013). The complete pathological response (pCR; ypT0N0) rate did not significantly differ between gem-carbo and gem-cis (20.7% versus 22.1%; p = 0.73). Chemotherapeutic regimen was not significantly associated with pCR (OR 0.99 [95%CI 0.61-1.59]; p = 0.96), overall survival (OS) (HR 1.20 [95%CI 0.85-1.67]; p = 0.31), or cancer-specific survival (CSS) (HR 1.35 [95%CI 0.93-1.96]; p = 0.11). Median OS of patients treated with gem-carbo and gem-cis was 28.6 months (95%CI 18.1-39.1) and 45.1 months (95%CI 32.7-57.6) (p = 0.18), respectively. Median CSS of patients treated with gem-carbo and gem-cis was 28.8 months (95%CI 9.8-47.8) and 71.0 months (95%CI median not reached) (p = 0.02), respectively. Subanalyses of the neoadjuvant and induction setting did not show significant survival differences., Conclusion: Our results show that a subset of cisplatin-ineligible patients with MIBC achieve pCR on gem-carbo and that survival outcomes seem comparable to gem-cis provided patients are able to receive ≥ 3 cycles and undergo RC., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: The benefit of neoadjuvant systemic therapy (NAST) is not yet supported by randomized controlled trials in upper tract urothelial carcinoma (UTUC), but the evidence is increasing. This narrative systematic review was conducted to evaluate the available evidence on the role of NAST in patients undergoing radical nephroureterectomy (RNU) for UTUC., Evidence Acquisition: We searched for all relevant articles or conference abstracts published and indexed in PubMed, Embase, and Scopus on July 19, 2021. The study was reported according to the PRISMA criteria and designed within the PICOS framework. We included studies comparing patients with non-metastatic UTUC who received neoadjuvant chemotherapy (NAC) or immunotherapy (NAI) with patients who underwent definitive surgery alone or surgery plus adjuvant systemic therapy. Prospective uncontrolled studies were also included., Evidence Synthesis: We identified 27 reports (NAC, N.=24 and NAI, N.=3) published between 2010 and 2021. Twenty of the 24 studies on NAC were retrospective comparative analyses, whereas the remaining four were prospective single-arm studies. One of the three NAI studies exclusively enrolled patients with UTUC. NAC was associated with improved survival and better pathological response relative to surgery alone, but there was no clear advantage when compared to surgery plus adjuvant chemotherapy. Overall, the drug-induced toxicity and risk of disease progression were acceptable but the inherent bias across study designs, inadequate reporting and heterogeneous definition of primary outcomes render it difficult to synthesize results, compare centers, and inform practice., Conclusions: The current level of evidence supporting NAST for UTUC is relatively low and the inability to predict responsiveness and thereby pinpoint the optimal candidates remains a major challenge. There is a need to compare NAST to adjuvant therapies using clearly defined primary endpoints as minimum reporting standards developed by a multidisciplinary team.

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 and Objectives: To assess efficacy and safety of Percutaneous Cryoablation (PCA) of small renal masses (SRMs) using Trifecta outcomes in a large cohort of patients who were not eligible for surgery. Materials and methods: All PCAs performed in four different centers between September 2009 and September 2019 were retrospectively evaluated. Patients were divided in two different groups depending on masses dimensional criteria: Group-A: diameter ≤ 25 mm and Group-B: diameter > 25 mm. Complications rates were reported and classified according to the Clavien−Dindo system. The estimate glomerular filtration rate (eGFR) was calculated before PCA and during follow-up schedule. Every patient received a Contrast Enhanced Ultrasound (CEUS) evaluation on the first postoperative day. Radiological follow-up was taken at 3, 6, and 12 months for the first year, then yearly. Radiological recurrence was defined as a contrast enhancement persistence and was reported in the study. Finally, Trifecta outcome, which included complications, RFS, and preservation of eGFR class, was calculated for every procedure at a median follow-up of 32 months. Results: The median age of the patients was 74 years. Group-A included 200 procedures while Group-B included 140. Seventy-eight patients were eligible for Trifecta evaluation. Trifecta was achieved in 69.6% of procedures in Group-A, 40.6% in Group-B (p = 0.02). We observed an increased rate of complication in Group-B (13.0% vs. 28.6; p < 0.001). However, 97.5% were

Background: Treatment paradigms for management of metastatic renal cell carcinoma (mRCC) are evolving. We examined impact of surgical metastasectomy on survival across in mRCC stratified by risk-group., Methods: Multicenter retrospective analysis from the Registry of Metastatic RCC database. The cohort was subdivided utilizing Motzer criteria (favorable-, intermediate-, high-risk). Primary outcome was all-cause mortality (ACM)/overall survival (OS); secondary outcome was cancer-specific mortality (CSM)/cancer-specific survival (CSS). Impact of metastasectomy was analyzed via Cox-Regression analysis adjusting for potential prognostic variables and Kaplan-Meier analysis (KMA) within each risk-group., Results: Four hundred thirty-one patients (59 favorable-risk, 274 intermediate-risk, 98 high-risk; median follow-up 27.2 months) were analyzed. Metastasectomy was performed in 22 (37%), 66 (24%), and 32 (16%) of favorable-, intermediate- and high-risk groups (P = .012). Median number of metastases at diagnosis differed significantly (favorable-risk 2, intermediate-risk 3.4, high-risk 5.1, P < .001). On Cox-regression, high-risk (HR = 1.72, P = .002) was associated with worsened ACM, while metastasectomy was associated with improved ACM (HR = 0.56, P = .005). On KMA, median OS (months) was longer with metastasectomy in favorable- (92.7 vs. 25.8, P = .003) and intermediate-risk (26.3 vs. 20.1, P = .038), but not high-risk (P = .911) groups. Metastasectomy was associated with longer CSS in favorable- (76.1 vs. 32.8, P = .004) but not intermediate- (P = .06) and high-risk (P = .595) groups., Conclusions: Metastasectomy was independently associated with improved ACM and CSM, as well as improved CSS and OS in favorable- and intermediate-risk mRCC patients. Metastasectomy may be considered as component of multimodal management strategy in favorable and intermediate-risk subgroups. In high-risk patients, metastasectomy should be deferred except in select circumstances., (Copyright © 2022. Published by Elsevier Inc.)

Objective: To determine whether use of neoadjuvant chemotherapy (NAC) is associated with a higher risk of post-operative complications following radical cystectomy (RC) for bladder cancer (BCa)., Materials and Methods: We retrospectively reviewed records of patients undergoing RC for non-metastatic urothelial BCa at 13 tertiary care centres from 2007-2019. Patients who received NAC ('NAC + RC' group) were compared with those who underwent upfront RC ('RC alone' group) for intra-operative variables, incidence of post-operative complications as per the Clavien-Dindo classification (CDC) and rates of re-admission and re-intervention. Multivariable logistic regression analysis was performed to determine predictors of CDC overall and CDC major (grade III-V) complications. We also analysed the trend of NAC utilization over the study period., Results: Of the 3113 patients included, 968 (31.1%) received NAC while the remaining 2145 (68.9%) underwent upfront RC for BCa. There was no significant difference between the NAC + RC and RC alone groups with regards to 30-day CDC overall (53.2% vs 54.6%, p = 0.4) and CDC major (15.5% vs 16.5%, p = 0.6) complications. The two groups were comparable for the rate of surgical re-intervention (14.6% in each group) and re-hospitalization (19.6% in NAC + RC vs 17.9% in RC alone, p = 0.2%) at 90 days. On multivariable regression analysis, NAC use was not found to be a significant predictor of 90-day CDC overall (OR 1.02, CI 0.87-1.19, p = 0.7) and CDC major (OR 1.05, CI 0.87-1.26, p = 0.6) complications. We also observed that the rate of NAC utilization increased significantly (p < 0.001) from 11.1% in 2007 to 41.2% in 2019, reaching a maximum of 48.3% in 2018., Conclusion: This large multicentre analysis with a substantial rate of NAC utilization showed that NAC use does not lead to an increased risk of post-operative complications following RC for BCa. This calls for increasing NAC use to allow patients to avail of its proven oncologic benefit., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Standard-of-care management of renal cell carcinoma (RCC) indisputably relies on surgery for low-risk localized tumours and systemic treatment for poor-prognosis metastatic disease, but a grey area remains, encompassing high-risk localized tumours and patients with metastatic disease with a good-to-intermediate prognosis. Over the past few years, results of major practice-changing trials for the management of metastatic RCC have completely transformed the therapeutic options for this disease. Treatments targeting vascular endothelial growth factor (VEGF) have been the mainstay of therapy for metastatic RCC in the past decade, but the advent of immune checkpoint inhibitors has revolutionized the therapeutic landscape in the metastatic setting. Results from several pivotal trials have shown a substantial benefit from the combination of VEGF-directed therapy and immune checkpoint inhibition, raising new hopes for the treatment of high-risk localized RCC. The potential of these therapeutics to facilitate the surgical extirpation of the tumour in the neoadjuvant setting or to improve disease-free survival in the adjuvant setting has been investigated. The role of surgery for metastatic RCC has been redefined, with results of large trials bringing into question the paradigm of upfront cytoreductive nephrectomy, inherited from the era of cytokine therapy, when initial extirpation of the primary tumour did show clinical benefits. The potential benefits and risks of deferred surgery for residual primary tumours or metastases after partial response to checkpoint inhibitor treatment are also gaining interest, considering the long-lasting effects of these new drugs, which encourages the complete removal of residual masses., (© 2022. Springer Nature Limited.)

In the last years the incidence of renal neoplasms has been steadily increasing, along with the average age of patients at the time of diagnosis. Surgical management for localized disease is becoming more challenging because of patients’ frailty. We conducted a multi-center prospective study to evaluate the role of the G8 as a screening tool in the assessment of intra and post-operative complications of elderly patients (≥70 y.o.) undergoing surgery for kidney cancer. A total of 162 patients were prospectively enrolled between January 2015 to January 2019 and divided into two study groups (frail vs. not-frail) according to their geriatric risk profile based on G8 score. Several factors (i.e., age, CCI, ASA score, preoperative anemia, RENAL score, surgical procedures, and techniques) were analyzed to identify whether any of them would configure as a statistically significant predictor of surgical complications. According to the G8 Score, 90 patients were included in the frail group. A total of 52 frail patients vs. 4 non-frail patients developed a postoperative complication of any kind (p < 0.001). Of these, 11 were major complications and all occurred in the frail group. Our results suggest that the G8 screening tool is an effective and useful instrument to predict the risk of overall complications in elderly patients prior to renal surgery.