ASO Visual Abstract: Open Versus Minimally Invasive Nephroureterectomy: Contemporary Analysis from a Wide National Population-Based Database.

Contemporary trend analysis of a large national data set confirms the occurrence of a significant shift toward minimally invasive nephroureterectomy (MINU), which is gradually replacing open nephroureterectomy (ONU). A minimally invasive approach is associated with a lower risk of complications. Social determinants of health (SDOH) are non-clinical factors that ultimately may have an impact on the outcomes of the nephroureterectomy (NU) procedure ( https://doi.org/10.1245/s10434-024-15565-6 ).

Robotic distal ureterectomy for high-risk distal ureteral urothelial carcinoma: a retrospective multicenter comparative analysis (ROBUUST 2.0 collaborative group).

BACKGROUND: The role of kidney-sparing surgery in patients with high-risk upper urinary tract urothelial carcinoma is controversial. The present study aimed to assess oncological and functional outcomes of robot-assisted distal ureterectomy in patients with high-risk distal ureteral tumors. METHODS: The ROBUUST 2.0 multicenter international (2015-2022) dataset was used for this retrospective cohort analysis. High-risk patients with distal ureteral tumors were divided based on type of surgery: robot-assisted distal ureterectomy or robot-assisted nephroureterectomy. A survival analysis was performed for local recurrence-free survival, distant metastasis-free survival, and overall survival. After adjusting for clinical features of the high-risk prognostic group, Cox proportional hazard model was plotted to evaluate significant predictors of time-to-event outcomes. RESULTS: Overall, 477 patients were retrieved, of which 58 received robot-assisted distal ureterectomy and 419 robot-assisted nephroureterectomy, respectively, with a mean (±SD) follow-up of 29.6 months (±2.6). The two groups were comparable in terms of baseline features. At survival analysis, no significant difference was observed in terms of recurrence-free survival (P=0.6), metastasis-free survival (P=0.5) and overall survival (P=0.7) between robot-assisted distal ureterectomy and robot-assisted nephroureterectomy. At Cox regression analysis, type of surgery was never a significant predictor of worse oncological outcomes. At last follow-up patients undergoing robot-assisted distal ureterectomy had significantly better postoperative renal function. CONCLUSIONS: Comparable outcomes in terms of recurrence-free survival, metastasis-free survival, and overall survival between robot-assisted distal ureterectomy and robot-assisted nephroureterectomy patients, and better postoperative renal function preservation in the former group were observed. Kidney-sparing surgery should be considered as a potential option for selected patients with high-risk distal ureteral UTUC.

Open versus Minimally Invasive Nephroureterectomy: Contemporary Analysis from a Wide National Population-Based Database.

BACKGROUND: It is generally perceived that minimally invasive nephroureterectomy (MINU), especially in the form of robotic-assisted laparoscopy, is gaining an increasing role in many institutions. OBJECTIVE: The aim of our study was to investigate contemporary trends in the adoption of MINU in the United States compared with open nephroureterectomy (ONU). METHODS: Patients who underwent ONU or MINU between 2011 and 2021 were retrospectively analyzed using PearlDiver Mariner, an all-payer insurance claims database. International Classification of Diseases diagnosis and procedure codes were used to identify the type of surgical procedure, patients' characteristics, social determinants of health (SDOH), and perioperative complications. The primary objective assessed different trends and costs in NU adoption, while secondary objectives analyzed factors influencing the postoperative complications, including SDOH. Outcomes were compared using multivariable regression models. RESULTS: Overall, 15,240 patients underwent ONU (n = 7675) and MINU (n = 7565). Utilization of ONU declined over the study period, whereas that of MINU increased from 29 to 72% (p = 0.01). The 60-day postoperative complication rate was 23% for ONU and 19% for MINU (p < 0.001). At multivariable analysis, ONU showed a significantly higher risk of postoperative complications (odds ratio 1.33, 95% CI 1.20-1.48). Approximately 5% and 9% of patients reported at least one SDOH at baseline for both ONU and MINU (p < 0.001). CONCLUSIONS: Contemporary trend analysis of a large national dataset confirms that there has been a significant shift towards MINU, which is gradually replacing ONU. A minimally invasive approach is associated with lower risk of complications. SDOH are non-clinical factors that currently do not have an impact on the outcomes of nephroureterectomy.

Decisional and prognostic impact of diagnostic ureteroscopy in high-risk upper tract urothelial carcinoma: A multi-institutional collaborative analysis (ROBUUST collaborative group).

BACKGROUND: Diagnostic ureteroscopy (URS) with or without biopsy remains a subject of contention in the management of upper tract urothelial carcinoma (UTUC), with varying recommendations across different guidelines. The study aims to analyse the decision-making and prognostic role of diagnostic ureteroscopy (URS) in high-risk UTUC patients undergoing curative surgery. MATERIALS AND METHODS: In this retrospective multi-institutional analysis of high-risk UTUC patients from the ROBUUST dataset, a comparison between patients who received or not preoperative URS and biopsy before curative surgery was carried out. Logistic regression analysis evaluated differences between patients receiving URS and its impact on treatment strategy. Survival analysis included 5-year recurrence-free survival (RFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS). After adjusting for high-risk prognostic group features, Cox proportional hazard model estimated significant predictors of time-to-event outcomes. RESULTS: Overall, 1,912 patients were included, 1,035 with preoperative URS and biopsy and 877 without. Median follow-up: 24 months. Robot-assisted radical nephroureterectomy was the most common procedure (55.1%), in both subgroups. The 5-year OS (P = 0.04) and CSS (P < 0.001) were significantly higher for patients undergoing URS. The 5-year RFS (P = 0.6), and MFS (P = 0.3) were comparable between the 2 groups. Preoperative URS and biopsy were neither a significant predictor of worse oncological outcomes nor of a specific treatment modality. CONCLUSIONS: The advantage in terms of OS and CSS in patients undergoing preoperative URS could derive from a better selection of candidates for curative treatment. The treatment strategy is likely more influenced by tumor features than by URS findings.

A Comprehensive Review on Upper Tract Urothelial Carcinoma: An Update in 2023.

It is our pleasure to serve as the guest editors for the Cancers journal for this Special Issue, titled "Comprehensive Review on Upper Tract Urothelial Carcinoma: An Update in 2023" [...].

Prophylactic Use of Biologic Mesh in Ileal Conduit (PUBMIC): A Randomized Clinical Trial.

PURPOSE: We assessed the effect of prophylactic biologic mesh on parastomal hernia (PSH) development in patients undergoing cystectomy and ileal conduit (IC). MATERIALS AND METHODS: This phase 3, randomized, controlled trial (NCT02439060) included 146 patients who underwent cystectomy and IC at the University of Southern California between 2015 and 2021. Follow-ups were physical exam and CT every 4 to 6 months up to 2 years. Patients were randomized 1:1 to receive FlexHD prophylactic biological mesh using sublay intraperitoneal technique vs standard IC. The primary end point was time to radiological PSH, and secondary outcomes included clinical PSH with/without surgical intervention and mesh-related complications. RESULTS: The 2 arms were similar in terms of baseline clinical features. All surgeries and mesh placements were performed without any intraoperative complications. Median operative time was 31 minutes longer in patients who received mesh, yet with no statistically significant difference (363 vs 332 minutes, P = .16). With a median follow-up of 24 months, radiological and clinical PSHs were detected in 37 (18 mesh recipients vs 19 controls) and 16 (8 subjects in both arms) patients, with a median time to radiological and clinical PSH of 8.3 and 15.5 months, respectively. No definite mesh-related adverse events were reported. Five patients (3 in the mesh and 2 in the control arm) required surgical PSH repair. Radiological PSH-free survival rates in the mesh and control groups were 74% vs 75% at 1 year and 69% vs 62% at 2 years. CONCLUSIONS: Implementation of biologic mesh at the time of IC construction is safe without significant protective effects within 2 years following surgery.

Surveillance of non-muscle-invasive bladder cancer with blue-light cystoscopy: a meta-analysis.

OBJECTIVE: To compare the value of flexible blue-light cystoscopy (BLC) vs flexible white-light cystoscopy (WLC) in the surveillance setting of non-muscle-invasive bladder cancer (NMIBC). METHODS: All major databases were searched for articles published before May 2023 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The primary outcome was the accuracy of flexible BLC vs WLC in detecting bladder cancer recurrence among suspicious bladder lesions. RESULTS: A total of 10 articles, comprising 1634 patients, were deemed eligible for the quantitative synthesis. In the meta-analysis focusing on the detection of disease recurrence, there was no difference between flexible BLC and WLC (odds ratio [OR] 1.08, 95% confidence interval [CI] 0.82-1.41)]; the risk difference (RD) showed 1% of flexible BLC, corresponding to a number needed to treat (NNT) of 100. In the subgroup meta-analysis of detection of carcinoma in situ (CIS) only, there was again no significant difference between flexible BLC and WLC (OR 1.19, 95% CI 0.82-1.69), BLC was associated with a RD of 2% (NNT = 50). The positive predictive values for flexible BLC and WLC in detecting all types of recurrence were 72% and 66%, respectively, and for CIS they were 39% and 29%, respectively. CONCLUSION: Surveillance of NMIBC with flexible BLC could detect more suspicious lesions and consequently more tumour recurrences compared to flexible WLC, with a increase in the rate of false positives leading to overtreatment. A total of 100 and 50 flexible BLC procedures would need to be performed to find on additional tumor and CIS recurences, respectively. A risk-stratified strategy for patient selection could be considered when using flexible BLC for the surveillance of NMIBC patients.

The effect of enhanced recovery after surgery on oncologic outcome following radical cystectomy for urothelial bladder carcinoma.

INTRODUCTION: Limited data are available regarding the effect of enhanced recovery after surgery (ERAS) protocols on the long-term outcomes of radical cystectomy (RC) in bladder cancer patients. The aim of this study is to evaluate the oncological outcomes in patients who underwent RC with ERAS protocol. METHODS: We reviewed the records of patients who underwent RC for primary urothelial bladder carcinoma with curative intent from January 2003 to August 2022. The primary and secondary outcomes were recurrence-free (RFS) and overall survival (OS). Multivariable Cox regression analysis was performed to evaluate the effect of ERAS on oncological outcomes. RESULTS: A total of 967 ERAS patients and 1144 non-ERAS patients were included in this study. The RFS rates at 1, 3, and 5 years after RC were 81%, 71.5%, and 69% in the ERAS cohort, respectively. This rate in the non-ERAS group was 81%, 71%, and 67% at 1, 3, and 5 years after RC, respectively (P = 0.50). However, ERAS patients had significantly better OS with 86%, 73%, and 67% survival rates at 1, 3, and 5 years compared to 84%, 68%, and 59.5% survival rates in the non-ERAS group, respectively (P = 0.002). In multivariable analysis adjusting for other relevant factors, ERAS was no longer independently associated with recurrence-free (HR = 0.96, 95% CI 0.76-1.22, P = 0.75) or overall survival (HR = 0.84, 95% CI 0.66-1.09, P = 0.28) following RC. CONCLUSION: ERAS protocols are associated with a shorter hospital stay, yet with no impact on long-term oncologic outcomes in patients undergoing RC for bladder cancer.

Blood-based liquid biopsy: A promising noninvasive test in diagnosis, surveillance, and prognosis of patients with upper tract urothelial carcinoma.

OBJECTIVES: To assess the efficacy of blood-based liquid biopsy in the diagnosis, surveillance, and prognosis of upper tract urothelial carcinoma (UTUC). METHODS AND MATERIALS: In this prospective study, peripheral blood samples were collected from patients with primary UTUC before surgery with curative intent and follow-up visits at University of Southern California between May 2021 and September 2022. The samples were analyzed using the third-generation comprehensive high-definition single-cell assay (HDSCA3.0) to detect rare events, including circulating tumor cells (CTCs) and oncosomes, based on the immunofluorescence signals of DAPI (D), cytokeratin (CK), CD45/CD31 (CD), and vimentin (V). The findings of pre-surgery liquid biopsies were compared with those of blood samples from normal donors (NDs) and matched follow-up liquid biopsies. The association between liquid biopsy findings and clinical data, including recurrence-free survival (RFS), was also assessed. RESULTS: Twenty-eight patients with UTUC were included, of whom 21 had follow-up samples. Significant differences in specific rare analytes were detected in the preoperative samples compared to the NDs. In the post- vs. presurgery matched analysis, a significant decrease was detected in total-, CK-, and CK|V oncosomes, as well as in D-, D|V-, and D|V|CD cells. With a median follow-up of 11 months, 8 patients had disease recurrence. Survival analysis demonstrated that patients with >1.95 preoperative CK|V oncosomes (p = 0.020) and those with >4.18 D|CK|V cells (p = 0.050) had worse RFS compared to other patients. CONCLUSIONS: This study demonstrated promising initial evidence for the biomarker role of CTCs and oncosomes in the diagnosis and surveillance of patients with UTUC.

Oncologic Outcomes in Patients with Residual Upper Tract Urothelial Carcinoma Following Neoadjuvant Chemotherapy.

BACKGROUND AND OBJECTIVE: Growing evidence supports the use of neoadjuvant chemotherapy (NAC) for upper tract urothelial carcinoma (UTUC). However, the implications of residual UTUC at radical nephroureterectomy (RNU) after NAC are not well characterized. Our objective was to compare oncologic outcomes for pathologic risk-matched patients who underwent RNU for UTUC who either received NAC or were chemotherapy-naïve. METHODS: We retrospectively identified 1993 patients (including 112 NAC recipients) who underwent RNU for nonmetastatic, high-grade UTUC between 1985 and 2022 in a large, international, multicenter cohort. We divided the cohort into low-risk and high-risk groups defined according to pathologic findings of muscle invasion and lymph node involvement at RNU. Recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS) estimates were calculated using the Kaplan-Meier method. Multivariable analyses were performed to determine clinical and demographic factors associated with these outcomes. KEY FINDINGS AND LIMITATIONS: Among patients with low-risk pathology at RNU, RFS, OS, and CSS were similar between the NAC and chemotherapy-naïve groups. Among patients with high-risk pathology at RNU, the NAC group had poorer RFS (hazard ratio [HR] 3.07, 95% confidence interval [CI] 2.10-4.48), OS (HR 2.06, 95% CI 1.33-3.20), and CSS (subdistribution HR 2.54, 95% CI 1.37-4.69) in comparison to the pathologic risk-matched, chemotherapy-naïve group. Limitations include the lack of centralized pathologic review. CONCLUSIONS AND CLINICAL IMPLICATIONS: Patients with residual invasive disease at RNU after NAC represent a uniquely high-risk population with respect to oncologic outcomes. There is a critical need to determine an optimal adjuvant approach for these patients. PATIENT SUMMARY: We studied a large, international group of patients with cancer of the upper urinary tract who underwent surgery either with or without receiving chemotherapy beforehand. We identified a high-risk subgroup of patients with residual aggressive cancer after chemotherapy and surgery who should be prioritized for clinical trials and drug development.

Competency in Robotic Surgery: Standard Setting for Robotic Suturing Using Objective Assessment and Expert Evaluation.

OBJECTIVE: Surgical skill assessment tools such as the End-to-End Assessment of Suturing Expertise (EASE) can differentiate a surgeon's experience level. In this simulation-based study, we define a competency benchmark for intraoperative robotic suturing using EASE as a validated measure of performance. DESIGN: Participants conducted a dry-lab vesicourethral anastomosis (VUA) exercise. Videos were each independently scored by 2 trained, blinded reviewers using EASE. Inter-rater reliability was measured with prevalence-adjusted bias-adjusted Kappa (PABAK) using 2 example videos. All videos were reviewed by an expert surgeon, who determined if the suturing skills exhibited were at a competency level expected for residency graduation (pass or fail). The Contrasting Group (CG) method was then used to set a pass/fail score at the intercept of the pass and fail cohorts' EASE score distributions. SETTING: Keck School of Medicine, University of Southern California. PARTICIPANTS: Twenty-six participants: 8 medical students, 8 junior residents (PGY 1-2), 7 senior residents (PGY 3-5) and 3 attending urologists. RESULTS: After 1 round of consensus-building, average PABAK across EASE subskills was 0.90 (Range 0.67-1.0). The CG method produced a competency benchmark EASE score of >35/39, with a pass rate of 10/26 (38%); 27% were deemed competent by expert evaluation. False positives and negatives were defined as medical students who passed and attendings who failed the assessment, respectively. This pass/fail score produced no false positives or negatives, and fewer JR than SR were considered competent by both the expert and CG benchmark. CONCLUSIONS: Using an absolute standard setting method, competency scores were set to identify trainees who could competently execute a standardized dry-lab robotic suturing exercise. This standard can be used for high stakes decisions regarding a trainee's technical readiness for independent practice. Future work includes validation of this standard in the clinical environment through correlation with clinical outcomes.

Prognostic Significance of Grade Discrepancy Between Primary Tumor and Venous Thrombus in Nonmetastatic Clear-cell Renal Cell Carcinoma: Analysis of the REMEMBER Registry and Implications for Adjuvant Therapy.

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.

Survival of Patients with Chronic Kidney Disease Treated with Radical Cystectomy and Risk Factors of Glomerular Filtration Rate Loss Following Radical Cystectomy: Two Systematic Reviews and Meta-analyses of Interplay Between Radical Cystectomy and Renal Function.

CONTEXT: There is no high-level evidence regarding the risk factors of glomerular filtration rate (GFR) loss following radical cystectomy (RC) and survival outcomes of patients with chronic kidney disease (CKD) undergoing RC. OBJECTIVE: To identify the risk factors of CKD in patients treated with RC for bladder cancer and to assess overall and oncological survival of patients with CKD who underwent RC. EVIDENCE ACQUISITION: According to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement, two systematic reviews were performed for studies published before September 30, 2022, assessing (1) risk factors of renal function (RF) decline following RC and (2) overall and oncological outcomes of CKD patients treated with RC. EVIDENCE SYNTHESIS: A total of 21 and 17 studies were included for qualitative and quantitative syntheses, respectively. The first meta-analysis of ten studies (15 502 patients) identified these factors to be significantly associated with GFR loss following RC: advanced age, lower baseline RF, higher Charlson Comorbidity Index (CCI), diabetes mellitus, hypertension, postoperative hydronephrosis, ureteroenteric stricture, and locally advanced disease (hazard ratios [HRs] 1.03, 1.22, 1.5, 1.27, 1.24, 1.69, 1.92, and 5.13, respectively), while sex, preoperative hydronephrosis, perioperative chemotherapy, and diversion type were not. The second meta-analysis of seven studies (6900 patients) demonstrated significantly worse metastasis-free, cancer-specific, and overall survival in patients with higher CKD stages than in those with lower stages (HRs 1.54, 2.09, and 1.47, respectively). CONCLUSIONS: Current evidence suggests that older age, lower baseline RF, higher CCI, diabetes mellitus, hypertension, postoperative hydronephrosis, ureteroenteric stricture, and locally advanced disease are associated with long-term GFR loss following RC. In addition, patients with higher stages of CKD have worse long-term overall and oncological outcomes following RC. These data may help in counseling and decision-making regarding therapy and preventive measures. PATIENT SUMMARY: Several factors have been identified that can help identify patients at risk for glomerular filtration rate loss after radical cystectomy (RC). Chronic kidney disease is associated with poor cancer- and non-cancer-specific outcomes following RC.

Immune Checkpoint Inhibitor Therapy Before Nephrectomy for Locally Advanced and Metastatic Renal Cell Carcinoma: A Review.

Importance: The therapeutic landscape of advanced renal cell carcinoma (RCC) has rapidly evolved in the past 2 decades, with the advent of cytokines therapy followed by targeted therapies and novel immune checkpoint inhibitors (ICI). This article aims to review the current evidence and ongoing trials of neoadjuvant or prenephrectomy ICI therapy in patients with locally advanced and metastatic RCC. Observations: A literature search was performed using the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and PubMed as well as relevant medical society meetings for English-language studies, articles, and abstracts published before January 31, 2023. Currently, level I evidence supports the use of ICI-based combination therapy as the first-line treatment of patients with metastatic RCC with the potential option of deferred nephrectomy in those who respond to treatment. Nevertheless, limited prospective data are available regarding the role and outcomes of nephrectomy (cytoreductive or consolidative) in conjunction with ICI therapy in both metastatic and locally advanced RCC. Although data from retrospective case series confirmed the feasibility and safety of deferred nephrectomy in this setting, the sequence of nephrectomy and whether it should be considered in patients with metastatic RCC is a common clinical dilemma. However, although neoadjuvant targeted therapy for nonmetastatic RCCs has been associated with some advantages yet not accepted as a standard, current data from a phase 3 randomized clinical trial failed to demonstrate the oncologic benefit of neoadjuvant nivolumab for locally advanced RCC. Conclusion and Relevance: The findings of this review suggest that ICI-based combination therapy is the standard of care as the first-line treatment of patients with metastatic RCC. However, the role of neoadjuvant ICIs in locally advanced RCC is an active area of investigation. Deferred nephrectomy after ICI-based immunotherapy for metastatic RCC is feasible and safe yet should be performed in high-volume health centers by experienced surgeons. The multidisciplinary and careful approach is critical for treatment decisions.