The impact of bladder cuff excision on outcomes after nephroureterectomy for upper tract urothelial carcinoma: An analysis of the ROBUUST 2.0 registry.

OBJECTIVES: We sought to determine whether bladder cuff excision and its technique influence outcomes after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS AND MATERIALS: A multicenter, international, retrospective analysis using the ROBotic surgery for Upper tract Urothelial cancer Study (ROBUUST) 2.0 registry identified 1,718 patients undergoing RNU for UTUC between 2015 and 2023 at 17 centers across the United States, Europe, and Asia. Data was gathered on (1) whether bladder cuff excision was performed and (2) what technique was used, including formal excision or other techniques (pluck technique, stripping/intussusception technique) and outcomes. Multivariate and survival analyses were performed to compare the groups. RESULTS: Most patients (90%, 1,540/1,718) underwent formal bladder cuff excision in accordance with EAU and AUA guidelines. Only 4% (68/1,718) underwent resection using other techniques, and 6% (110/1,718) did not have a bladder cuff excised. Median follow up for the cohort was 24 months (IQR 9-44). When comparing formal bladder cuff excision to other excision techniques, there were no differences in oncologic or survival outcomes including bladder recurrence-free survival (BRFS), recurrence-free survival (RFS), metastasis-free survival (MFS), overall survival (OS), or cancer-specific survival (CSS). However, excision of any kind conferred a decreased risk of bladder-specific recurrence compared to no excision. There was no difference in RFS, MFS, OS, or CSS when comparing bladder cuff excision, other techniques, and no excision. CONCLUSIONS: Bladder cuff excision improves recurrence-free survival, particularly when considering bladder recurrence. This benefit is conferred regardless of technique, as long as the intramural ureter and ureteral orifice are excised. However, the benefit of bladder cuff excision on metastasis-free, overall, and cancer-specific survival is unclear.

Association of Tumor-informed Circulating Tumor DNA Detectability Before and After Radical Cystectomy with Disease-free Survival in Patients with Bladder Cancer.

BACKGROUND AND OBJECTIVE: Despite curative-intent radical cystectomy (RC), patients with muscle-invasive bladder cancer (MIBC) are at high risk of recurrence. Biomarkers are urgently needed to refine prognostication and selection of appropriate perioperative systemic therapies. Our aim was to evaluate the prognostic and predictive value of tumor-informed circulating tumor DNA (ctDNA) results in a multicenter cohort of patients with bladder cancer who underwent RC. METHODS: We performed a retrospective analysis of real-world data for a commercial ctDNA test (Signatera; Natera, Austin, TX, USA) performed in 167 patients (852 plasma samples) before RC and during molecular residual disease (MRD; adjuvant decision) and surveillance windows. We assessed the correlation between recurrence and ctDNA status before and after RC using Cox regression analysis. RESULTS AND LIMITATIONS: During study-defined postoperative MRD and surveillance windows, detectable ctDNA was associated with shorter disease-free survival (DFS) when compared to undetectable ctDNA (MRD: hazard ratio 6.93; p < 0.001; surveillance: hazard ratio 23.02; p < 0.001). Of note, patients with undetectable ctDNA did not appear to benefit from adjuvant therapy (p = 0.34). Detectable ctDNA in the pre-RC (p = 0.045), MRD (p = 0.002), and surveillance (p < 0.001) windows was the only risk factor independently associated with shorter DFS. Limitations include the retrospective and nonrandomized nature of the study. CONCLUSIONS: ctDNA testing in patients with bladder cancer undergoing RC was prognostic and potentially predictive. Identification of patients at high risk of recurrence may aid in patient counseling and decision-making. PATIENT SUMMARY: We found that outcomes for patients with muscle-invasive bladder cancer are strongly linked to detection of tumor DNA in blood samples. The results show the value of tumor-informed testing for tumor DNA in blood for decisions on the best treatment for each individual patient.

Prognostic factors and treatment impact on overall survival in patients with renal neuroendocrine tumour.

Background: Renal neuroendocrine neoplasms (R-NEN) are exceptionally rare tumours characterized by high mortality rates. Objective: The objective of this study is to analyse prognostic factors and treatment impact on overall survival in patients with R-NEN. Design setting and participants: We identified all patients with R-NEN in the National Cancer Database (NCDB) from 2004 to 2019 and identified prognostic factors for improved survival. Results and limitations: Of 542 R-NEN cases, 166 (31%) were neuroendocrine tumour grade 1 (NET-G1), 14 (3%) were neuroendocrine tumour grade 2 (NET-G2), 169 (31%) were neuroendocrine carcinoma (NEC-NOS), 18 (3%) were large cell neuroendocrine carcinoma (LC-NEC) and 175 (32%) were small cell neuroendocrine carcinoma (SC-NEC). Median overall survival for all patients in the study was 44.88 months (SE, 4.265; 95% CI, 27.57-62.19). Median overall survival was 7.89 months (SE 0.67; 95% CI, 6.58-9.20) for patients without surgical intervention and 136.61 months (SE 16.44; 95% CI, 104.38-168.84, p < 0.001) for patients who underwent surgery. Increased age (HR, 1.05; 95% CI, 1.03-1.06; p < 0.001), T4 stage disease (HR, 3.17; 95% CI, 1.96-5.1; p < 0.001), NEC-NOS histology (HR, 2.82; 95% CI, 1.64-4.86; p < 0.001), LC-NEC histology (HR, 2.73; 95% CI, 1.04-7.17; p = 0.041) and SC-NEC histology (HR, 5.17; 95% CI, 2.95-9.05; p < 0.001) were all positive predictors of worsening overall survival. The main limitation of the study is its retrospective design. Conclusion: R-NEN is an aggressive tumour characterized by high mortality rates. Surgery continues to be the mainstay of treatment and has shown to provide a survival benefit for most patients. Patient Summary: R-NEN is composed of several tumour histologies that differ based on their aggressiveness with NEC-NOS and SC-NEC being the most lethal. Surgery, predominantly through minimally invasive approaches, is the mainstay of treatment and has a clear survival benefit.

Urine scRNAseq reveals new insights into the bladder tumor immune microenvironment.

Due to bladder tumors' contact with urine, urine-derived cells (UDCs) may serve as a surrogate for monitoring the tumor microenvironment (TME) in bladder cancer (BC). However, the composition of UDCs and the extent to which they mirror the tumor remain poorly characterized. We generated the first single-cell RNA-sequencing of BC patient UDCs with matched tumor and peripheral blood mononuclear cells (PBMC). BC urine was more cellular than healthy donor (HD) urine, containing multiple immune populations including myeloid cells, CD4+ and CD8+ T cells, natural killer (NK) cells, B cells, and dendritic cells (DCs) in addition to tumor and stromal cells. Immune UDCs were transcriptionally more similar to tumor than blood. UDCs encompassed cytotoxic and activated CD4+ T cells, exhausted and tissue-resident memory CD8+ T cells, macrophages, germinal-center-like B cells, tissue-resident and adaptive NK cells, and regulatory DCs found in tumor but lacking or absent in blood. Our findings suggest BC UDCs may be surrogates for the TME and serve as therapeutic biomarkers.

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.

Induction and maintenance of sequential intravesical gemcitabine/docetaxel for intermediate and high-risk non-muscle invasive bladder cancer with different dosage protocols.

INTRODUCTION: The combination of sequential intravesical gemcitabine and docetaxel (Gem/Doce) chemotherapy has been considered a feasible option for BCG (Bacillus Calmette-Guérin) treatment in non-muscle invasive bladder cancer (NMIBC), gaining popularity during BCG shortage period. We seek to determine the efficacy of the treatment by comparing Gem/Doce induction alone vs induction with maintenance, and to evaluate the treatment outcomes of two different dosage protocols. METHODS: A bi-center retrospective analysis of consecutive patients treated with Gem/Doce for NMIBC between 2018 and 2023 was performed. Baseline characteristics, risk group stratification (AUA 2020 guidelines), pathological, and surveillance reports were collected. Kaplan-Meier survival analysis was performed to detect Recurrence-free survival (RFS). RESULTS: Overall, 83 patients (68 males, 15 females) with a median age of 73 (IQR 66-79), and a median follow-up time of 18 months (IQR 9-25), were included. Forty-one had an intermediate-risk disease (49%) and 42 had a high-risk disease (51%). Thirty-seven patients (45%) had a recurrence; 19 (23%) had a high-grade recurrence. RFS of Gem/Doce induction-only vs induction + maintenance was at 6 months 88% vs 100%, at 12 months 71% vs 97%, at 18 months 57% vs 91%, and at 24 months 31% vs 87%, respectively (log-rank, p < 0.0001). Patients who received 2 g Gemcitabine with Docetaxel had better RFS for all-grade recurrences (log-rank, p = 0.017). However, no difference was found for high-grade recurrences. CONCLUSION: Gem/Doce induction with maintenance resulted in significantly better RFS than induction-only. Combining 2 g gemcitabine with docetaxel resulted in better RFS for all-grade but not for high-grade recurrences. Further prospective trials are necessary to validate our results.

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.

The role of preoperative immune cell metrics in renal cell carcinoma with a tumor thrombus.

INTRODUCTION: The objective of this study was to stratify preoperative immune cell counts by cancer specific outcomes in patients with renal cell carcinoma (RCC) and a tumor thrombus after radical nephrectomy with tumor thrombectomy. METHODS: Patients with a diagnosis of RCC with tumor thrombus that underwent radical nephrectomy with thrombectomy across an international consortium of seven institutions were included. Patients who were metastatic at diagnosis and those who received preoperative medical treatment were also included. Retrospective chart review was performed to collect demographic information, past medical history, preoperative lab work, surgical pathology, and follow up data. Neutrophil counts, lymphocyte counts, monocyte counts, neutrophil to lymphocyte ratios (NLR), lymphocyte to monocyte ratios (LMR), and neutrophil to monocyte ratios (NMR) were compared against cancer-specific outcomes using independent samples t-test, Pearson's bivariate correlation, and analysis of variance. RESULTS: One hundred forty-four patients were included in the study, including nine patients who were metastatic at the time of surgery. Absolute lymphocyte count preoperatively was greater in patients who died from RCC compared to those who did not (2 vs 1.4; p < 0.001). Patients with tumor pathology showing perirenal fat invasion had a greater neutrophil count compared to those who did not (7.5 vs 5.5; p = 0.010). Patients with metastatic RCC had a lower LMR compared to those without metastases after surgery (2.5 vs 3.2; p = 0.041). Tumor size, both preoperatively and on gross specimen, had an interaction with multiple immune cell metrics (p < 0.05). CONCLUSIONS: Preoperative immune metrics have clinical utility in predicting cancer-specific outcomes for patients with RCC and a tumor thrombus. Additional study is needed to determine the added value of preoperative serum immune cell data to established prognostic risk calculators for this patient population.

Thromboembolic Events After Robotic Radical Cystectomy: A Comparative Analysis of Extended and Limited Prophylaxis.

OBJECTIVE: To compare limited (only inpatient) venous thromboembolism (VTE) prophylaxis after robot-assisted radical cystectomy (RARC) to limited plus extended prophylaxis. There is little consensus on postoperative VTE prophylaxis regimens after RARC with data mostly extrapolated from other cancers. METHODS: Retrospective review of all RARC patients at our center between 2014-2022, identifying two groups: patients after a prospectively implemented protocol (January 2018 to present) utilizing a prolonged 21-day postoperative course of either enoxaparin 40 mg daily or apixaban 2.5 mg twice daily after discharge, or patients prior to January 2018 receiving only limited VTE prophylaxis during their immediate postoperative inpatient stay. PRIMARY OUTCOME: incidence of symptomatic VTE confirmed with imaging within 90-days postoperatively. SECONDARY OUTCOMES: major hemorrhage, complications, readmission, and mortality within 30-days postoperatively. Descriptive statistics depicted baseline patient characteristics, operative information, and complications. Differences were compared between groups. Logistic regression was used to determine associations between variables and primary outcome. RESULTS: Eighty-six patients received limited prophylaxis and 364 received extended prophylaxis. Twelve (2.7%) patients experienced VTE within 90-day postoperatively: (10 [2.7%] extended vs 2 [2.3%] limited, P = .9). Upon stratification into EAU "low-risk" or "high +intermediate-risk" groups, no statistically significant difference in VTE rates was seen between the extended or limited groups. When controlling for prophylaxis regimen, intracorporeal approach was found to be predictive of a lower with a lower risk of VTE (P = .019). CONCLUSION: Limited and extended prophylaxis showed no significant differences in VTE rates among RARC patients. Further studies are necessary for RARC patients to improve guidelines.

Robotic-assisted radical cystectomy with cutaneous ureterostomies: a contemporary multicenter analysis.

BACKGROUND: Robotic-assisted radical cystectomy (RARC) offers decreased blood loss during surgery, shorter hospital length of stay, and lower risk for thromboembolic events without hindering oncological outcomes. Cutaneous ureterostomies (UCS) are a seldom utilized diversion that can be a suitable alternative for a selected group of patients with competing co-morbidities and limited life expectancy. OBJECTIVE: To describe operative and perioperative characteristics as well as oncological outcomes for patients that underwent RARC + UCS. METHODS: Patients that underwent RARC + UCS during 2013-2023 in 3 centers (EU = 2, US = 1) were identified in a prospectively maintained database. Baseline characteristics, pathological, and oncological outcomes were analyzed. Descriptive statistics and survival analysis were performed using R language version 4.3.1. RESULTS: Sixty-nine patients were included. The median age was 77 years (IQR 70-80) and the median follow-up time was 11 months (IQR 4-20). Ten patients were ASA 4 (14.5%). Nine patients underwent palliative cystectomy (13%). The median operation time was 241 min (IQR 202-290), and the median hospital stay was 8 days (IQR 6-11). The 30-day complication rate was 55.1% (grade ≥ 3a was 14.4%), and the 30-day readmission rate was 17.4%. Eleven patients developed metastatic recurrence (15.9%), and 14 patients (20.2%) died during the follow-up period. Overall survival at 6, 12, and 24 months was 84%, 81%, and 73%, respectively. CONCLUSIONS: RARC + UCS may offer lower complication and readmission rates without the need to perform enteric anastomosis, it can be considered in a selected group of patients with competing co-morbidities, or limited life expectancy. Larger prospective studies are necessary to validate these results.

Longitudinal Tumor-informed Circulating Tumor DNA Status Predicts Disease Upstaging and Poor Prognosis for Patients Undergoing Radical Cystectomy.

BACKGROUND AND OBJECTIVE: Decision-making on the use of neoadjuvant and adjuvant treatment for patients with bladder cancer undergoing radical cystectomy (RC) currently depends on assessment of clinical and pathological features, which lack sensitivity. Circulating tumor DNA (ctDNA) has emerged as a possible novel prognostic biomarker in the field. Our aim was to assess whether ctDNA status before RC is predictive of pathological and oncological outcomes. We also evaluated the dynamic changes in ctDNA status after RC in relation to recurrence-free survival (RFS). METHODS: We analyzed data for patients who underwent RC during 2021-2023 for whom prospective tumor-informed ctDNA analyses were conducted before and after RC. RFS was evaluated using the Kaplan-Meier method. Predictors for disease recurrence were assessed using Cox proportional-hazards models. Pathological outcomes associated with detectable ctDNA before RC were assessed in univariable and multivariable regression analyses. KEY FINDINGS AND LIMITATIONS: We included 112 patients in the analysis. Median follow-up was 8 mo (interquartile range 4-13). ctDNA was detected before RC in 59 patients (53%) and was associated with poor RFS (log-rank p < 0.0001). Detectable ctDNA before RC was associated with poor outcomes regardless of clinical stage (

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.

Novel signatures of prostate cancer progression and therapeutic resistance.

INTRODUCTION: The extensive heterogeneity of prostate cancer (PCa) and multilayered complexity of progression to castration-resistant prostate cancer (CRPC) have contributed to the challenges of accurately monitoring advanced disease. Profiling of the tumor microenvironment with large-scale transcriptomic studies have identified gene signatures that predict biochemical recurrence, lymph node invasion, metastases, and development of therapeutic resistance through critical determinants driving CRPC. AREAS COVERED: This review encompasses understanding of the role of different molecular determinants of PCa progression to lethal disease including the phenotypic dynamic of cell plasticity, EMT-MET interconversion, and signaling-pathways driving PCa cells to advance and metastasize. The value of liquid biopsies encompassing circulating tumor cells and extracellular vesicles to detect disease progression and emergence of therapeutic resistance in patients progressing to lethal disease is discussed. Relevant literature was added from PubMed portal. EXPERT OPINION: Despite progress in the tumor-targeted therapeutics and biomarker discovery, distant metastasis and therapeutic resistance remain the major cause of mortality in patients with advanced CRPC. No single signature can encompass the tremendous phenotypic and genomic heterogeneity of PCa, but rather multi-threaded omics-derived and phenotypic markers tailored and validated into a multimodal signature.

Contemporary outcomes of patients undergoing robotic-assisted radical cystectomy: A comparative analysis between intracorporeal ileal conduit and neobladder urinary diversions.

Objective: We aimed to compare perioperative and oncologic outcomes for patients undergoing robotic-assisted radical cystectomy (RARC) with intracorporeal ileal conduit (IC) and neobladder (NB) urinary diversion. Methods: Patients undergoing RARC with intracorporeal urinary diversion between January 2017 and January 2022 at the Icahn School of Medicine at Mount Sinai, New York, NY, USA were indexed. Baseline demographics, clinical characteristics, perioperative, and oncologic outcomes were analyzed. Survival was estimated with Kaplan-Meier plots. Results: Of 261 patients (206 [78.9%] male), 190 (72.8%) received IC while 71 (27.2%) received NB diversion. Median age was greater in the IC group (71 [interquartile range, IQR 65-78] years vs. 64 [IQR 59-67] years, p<0.001) and BMI was 26.6 (IQR 23.2-30.4) kg/m2. IC group was more likely to have prior abdominal or pelvic radiation (15.8% vs. 2.8%, p=0.014). American Association of Anesthesiologists scores were comparable between groups. The IC group had a higher proportion of patients with pathological tumor stage 2 (pT2) tumors (34 [17.9%] vs. 10 [14.1%], p=0.008) and pathological node stages pN2-N3 (28 [14.7%] vs. 3 [4.2%], p<0.001). The IC group had less median operative time (272 [IQR 246-306] min vs. 341 [IQR 303-378] min, p<0.001) and estimated blood loss (250 [150-500] mL vs. 325 [200-575] mL, p=0.002). Thirty- and 90-day complication rates were 44.4% and 50.2%, respectively, and comparable between groups. Clavien-Dindo grades 3-5 complications occurred in 27 (10.3%) and 34 (13.0%) patients within 30 and 90 days, respectively, with comparable rates between groups. Median follow-up was 324 (IQR 167-552) days, and comparable between groups. Kaplan-Meier estimate for overall survival at 24 months was 89% for the IC cohort and 93% for the NB cohort (hazard ratio 1.23, 95% confidence interval 1.05-2.42, p=0.02). Kaplan-Meier estimate for recurrence-free survival at 24 months was 74% for IC and 87% for NB (hazard ratio 1.81, 95% confidence interval 0.82-4.04, p=0.10). Conclusion: Patients undergoing intracorporeal IC urinary diversion had higher postoperative cancer stage, increased nodal involvement, similar complications outcomes, decreased overall survival, and similar recurrence-free survival compared to patients undergoing RARC with intracorporeal NB urinary diversion.

Gemcitabine and cisplatin plus nivolumab as organ-sparing treatment for muscle-invasive bladder cancer: a phase 2 trial.

Cystectomy is a standard treatment for muscle-invasive bladder cancer (MIBC), but it is life-altering. We initiated a phase 2 study in which patients with MIBC received four cycles of gemcitabine, cisplatin, plus nivolumab followed by clinical restaging. Patients achieving a clinical complete response (cCR) could proceed without cystectomy. The co-primary objectives were to assess the cCR rate and the positive predictive value of cCR for a composite outcome: 2-year metastasis-free survival in patients forgoing immediate cystectomy or

Infections After Adoption of Antibiogram-directed Prophylaxis and Intracorporeal Urinary Diversion for Robot-assisted Radical Cystectomy.

BACKGROUND: Enhanced recovery after surgery (ERAS) has significantly decreased the morbidity associated with radical cystectomy. However, infectious complications including sepsis, urinary tract (UTIs), wound (WIs), and intra-abdominal (AIs) infections remain common. OBJECTIVE: To assess whether intracorporeal urinary diversion (ICUD) and antibiogram-directed antimicrobial prophylaxis would decrease infections after robotic-assisted radical cystectomy (RARC). DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis was performed of a prospectively maintained database of patients undergoing RARC between 2014 and 2022 at a tertiary care institution, identifying two groups based on adherence to a prospectively implemented modified ERAS protocol for RARC: modified-ERAS-ICUD and antibiogram-directed ampicillin-sulbactam, gentamicin, and fluconazole prophylaxis were utilized (from January 2019 to present time), and unmodified-ERAS-extracorporeal urinary diversion (UD) and guideline-recommended cephalosporin-based prophylaxis regimen were utilized (from November 2014 to June 2018). Patients receiving other prophylaxis regimens were excluded. INTERVENTION: ICUD and antibiogram-directed infectious prophylaxis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was UTIs within 30 and 90 d postoperatively. The secondary outcomes were WIs, AIs, and sepsis within 30 and 90 d postoperatively, and Clostridioides difficile infection (CDI) within 90 d postoperatively. RESULTS AND LIMITATIONS: A total of 396 patients were studied (modified-ERAS: 258 [65.2%], unmodified-ERAS: 138 [34.8%]). UD via a neobladder was more common in the modified-ERAS cohort; all other intercohort demographic differences were not statistically different. Comparing cohorts, modified-ERAS had significantly reduced rates of 30-d (7.8% vs 15.9%, p = 0.027) and 90-d UTIs (11.2% vs 25.4%, p = 0.001), and 30-d WIs (1.2% vs. 8.7%, p < 0.001); neither group had a WI after 30 d. Rates of AIs, sepsis, and CDI did not differ between groups. On multivariate regression, the modified-ERAS protocol correlated with a reduced risk of UTIs and WIs (all p < 0.01). The primary limitation is the retrospective study design. CONCLUSIONS: Utilization of ICUD and antibiogram-based prophylaxis correlates with significantly decreased UTIs and WIs after RARC. PATIENT SUMMARY: In this study of infections after robotic radical cystectomy for bladder cancer, we found that intracorporeal (performed entirely inside the body) urinary diversion and an institution-specific antibiogram-directed antibiotic prophylaxis regimen led to fewer urinary tract infections and wound infections at our institution.

Eliminating the routine use of postoperative drain placement in patients undergoing robotic-assisted radical cystectomy with intracorporeal urinary diversion.

INTRODUCTION: Perioperative management of patients undergoing radical cystectomy and urinary diversion utilizing both open and minimally invasive techniques have routinely included the use of drains in the operative field. We herein demonstrate the safety of robotic-assisted radical cystectomy (RARC) without the routine use of postoperative drains. METHODS: Patients who underwent drainless RARC with intracorporeal urinary diversion between 2017 and 2022 at our institution were reviewed. Baseline and clinical characteristics as well as perioperative and postoperative outcomes were analyzed. The primary study outcome was incidence of postoperative urinary leak or intra-abdominal infectious collections within 90 days of RARC. A univariate and multivariable logistic regression analysis was performed to determine associations between study variables and the primary outcome. RESULTS: Of 381 patients, 298 (78.2%) were male and median age and BMI were 68 (63, 76) and 26.2 [23.0, 29.8], respectively. Overall 30 and 90-day complication rates were 39.6% and 50.4%, respectively. Twenty-one (5.5%) patients experienced a urine leak or intra-abdominal infectious collections. Sub-group analysis of patients who experienced the primary outcome demonstrated median postoperative day of presentation was day 19, and this group required 16 total additional procedures. On multivariable logistic regression analysis, only prior radiation therapy was associated with the development of the primary outcome of urinary leak or intra-abdominal infectious collection (odds ratio: 15.12, 95% confidence interval [1.52-156.8], p = 0.02). CONCLUSION: Drainless RARC with totally intracorporeal urinary diversion achieved competitive perioperative and complications outcomes compared to prior open and robotic series. In the context of a larger enhanced recovery after surgery protocol in RARC patients, the routine use of drains may be safely omitted.

Clinical Significance of Extracellular Vesicles in Prostate and Renal Cancer.

Extracellular vesicles (EVs)-including apoptotic bodies, microvesicles, and exosomes-are released by almost all cell types and contain molecular footprints from their cell of origin, including lipids, proteins, metabolites, RNA, and DNA. They have been successfully isolated from blood, urine, semen, and other body fluids. In this review, we discuss the current understanding of the predictive value of EVs in prostate and renal cancer. We also describe the findings supporting the use of EVs from liquid biopsies in stratifying high-risk prostate/kidney cancer and advanced disease, such as castration-resistant (CRPC) and neuroendocrine prostate cancer (NEPC) as well as metastatic renal cell carcinoma (RCC). Assays based on EVs isolated from urine and blood have the potential to serve as highly sensitive diagnostic studies as well as predictive measures of tumor recurrence in patients with prostate and renal cancers. Overall, we discuss the biogenesis, isolation, liquid-biopsy, and therapeutic applications of EVs in CRPC, NEPC, and RCC.