Effects of Intraoperative Opioid Use and a Combined Anesthesia Protocol in Patients Undergoing Radical Cystectomy for Urothelial Carcinoma of the Bladder-A Single-Center Experience.

BACKGROUND: An increased intraoperative opioid dose seems to lead to worse outcomes in several types of cancer. We assessed the effect of intraoperatively administered opioids as well as the type of anesthesia on survival, recurrence rates and major perioperative outcomes in patients who underwent radical cystectomy (RC) for urothelial carcinoma of the urinary bladder. METHODS: We included patients who underwent open RC at our center between 2015 and 2022. The role of the type and dosage of intraoperative opioid agents, such as remifentanil, sufentanil and morphine milligram equivalents (MME), as well as the type of anesthesia (intravenous only versus intravenous/epidural), was assessed regarding perioperative and long-term outcomes after RC. RESULTS: A total of 508 patients with a median age of 73 years (IQR: 64-78) were included. Overall, 92 (18%) patients received intravenous anesthesia, whereas 416 (82%) received combined anesthesia. At a median follow-up of 270 days (IQR: 98-808), 108 (21%) deaths and 106 (21%) recurrences occurred. Combined anesthesia was associated with better survival (HR:0.63, 95% CI: 0.4-0.97, p = 0.037) and lower intensive care unit admission rates (OR: 0.49, 95% CI: 0.31-0.77, p = 0.002) in the univariate analysis (unadjusted). The type and dosage of intraoperative opioid agents did not affect long-term survival and recurrence rates, as well as major perioperative outcomes. Nevertheless, the findings of our study were limited by its single-center, retrospective design. CONCLUSION: The use of intraoperative opioids was not associated with worse outcomes in our cohort, while the use of additional epidural anesthesia seems to be beneficial in terms of overall survival and intensive care unit admissions. Nevertheless, further research is mandatory to validate the safety of opioids in patients undergoing RC.

Improved bladder diagnostics using multiparametric ultrasound.

This comprehensive review examines recent advancements in the integration of multiparametric ultrasound for diagnostic imaging of the urinary bladder. It not only highlights the current state of ultrasound imaging but also projects its potential to further elevate standards of care in managing urinary bladder pathologies. Specifically, contrast-enhanced ultrasound (CEUS) and elastography show significant improvements in detecting bladder tumors and assessing bladder wall mechanics compared to traditional methods. The review also explores the future potential of ultrasound-mediated nanobubble destruction (UMND) as an investigational targeted cancer therapy, showcasing a novel approach that utilizes nanobubbles to deliver therapeutic genes into tumor cells with high precision. Emerging AI-driven innovations and novel techniques, such as microvascular ultrasonography (MVUS), are proving to be powerful tools for the non-invasive and precise management of bladder conditions, offering detailed insights into bladder structure and function. These advancements collectively underscore their transformative impact on the field of urology.

Outcomes and Prognostic Factors of Patients with Urothelial Carcinoma Undergoing Radical Cystectomy and pT0 in the Final Histology Without Neoadjuvant Chemotherapy.

Purpose: Absence of tumor in the final histopathology after radical cystectomy (RC) is a rare but potentially favorable outcome. Therefore, we aimed to analyze outcomes and prognostic factors of patients with urothelial carcinoma (UC) undergoing RC and T0 in the final histology without neoadjuvant chemotherapy at a high-volume academic center. Patients and Methods: We retrospectively analyzed patients undergoing RC for pure UC between 2004 and 2020. Cancer-specific survival (CSS) and overall survival (OS) were calculated using Kaplan-Meier analysis and group comparison by Log rank test. Potential prognostic factors were analyzed using univariate Cox regression models. Results: A total of 1051 patients with UC underwent RC. 72 patients (6.7%) showed pT0 in the final histology. Across all T-stages, 5-year CSS was significantly different with 88% for pT0, 80% for pTa/pTis, 78% for pT1, 76% for pT2, 51% for pT3 and 27% for pT4 in our cohort (p=0.001). Neither instillation therapy (HR 0.31, 95% CI 0.07-1.43), number of TURB prior RC (HR 1.47, 95% CI 0.25-6.18), use of photodynamic diagnostics (PDD) (HR 0.64, 95% CI 0.14-3.02), performing a second resection (HR 0.87, 95% CI 0.27-2.86), muscle-invasive disease prior RC at any TURB (HR 0.7, 95% CI 0.2-2.39) or muscle-invasive disease in the TURB prior RC (HR 1.0, 0.31-3.29) were associated with CSS in univariate analysis. Conclusion: pT0 reveals a survival benefit in patients undergoing RC for UC and therefore presents a distinctive tumor entity. As clinical and cystoscopic characteristics do not improve patient stratification, further research is warranted to define risk groups in this specific tumor entity.

Long-term Health-related Quality of Life (HRQOL) After Radical Cystectomy and Urinary Diversion - A Propensity Score-matched Analysis.

INTRODUCTION: Radical cystectomy (RC) and urinary diversion by ileal conduit (IC) or ileal orthotopic neobladder (ONB) is the standard-of-care for surgical treatment of muscle-invasive bladder cancer. Yet, it is unclear how urinary diversion affects the patient's health-related quality of life (HRQOL) in the longer-term. METHODS: HRQOL was assessed preoperatively, 3mo postoperatively and then annually until a maximum follow-up of 48 months using the validated EORTC QLQ-C30- as well as the bladder cancer-specific FACT-BL- and QLQ-BLM30-questionnaires. A propensity-score matching for the variables "age," "ASA-classification," "cardiovascular co-morbidity," "sex" as well as "tumor stage," and "preoperative physical functioning score" was performed. Hypothetical predictors for decreased general HRQOL were analyzed using multivariable logistic regression models. RESULTS: After propensity-score matching, 246 patients were analyzed. HRQOL assessment revealed significant differences regarding preoperative QLQ-C30 symptoms which diminished during the postoperative time course. Similarly, we did not find significant differences based on bladder cancer-specific FACT-BL and QLQ-BLM HRQOL assessment including body image (48 months: 29.6.4 [IC] vs. 40.7 [ONB]; P = .733). Regarding general HRQOL, we found increased global health status scores for ONB throughout the whole observational period without reaching statistical significance (48 months: 55.0 [IC] vs. 70.1 [ONB]; P = .079). In multivariate analysis, cardiovascular comorbidity was an independent predictor of impaired HRQOL 24 months (HR 2.20; CI95% 1.02-5.72, P = .044) and 36 months (HR 6.84; CI95% 1.61-29.14, P = .009) postoperatively. CONCLUSION: We did not observe significant differences in bladder-specific as well as generic HRQOL in the longer-term and consequently, the type of urinary diversion was not an independent predictor of good general HRQOL in a follow-up period of 4 years.

Salvage cystectomy and ileal conduit urinary diversion as a last-line option for benign diseases-perioperative safety and postoperative health-related quality of life.

AIMS: Radical cystectomy and urinary diversion impact various dimensions of patients' health-related-quality-of-life (HRQOL). Yet, less is known about salvage cystectomy as a last-line option for treatment-refractory benign diseases. Therefore, our aim is to provide HRQOL data from a contemporary cohort of open salvage cystectomies for benign conditions. METHODS: Fifty-four consecutive patients were enrolled in one single tertiary referral center. Analysis was limited to patients undergoing urinary diversion via ileal conduit (IC). Complications were assessed via Clavien-Dindo-scale. HRQOL was measured using the validated European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-BLM30 questionnaire. HRQOL QLQ-C30 domains were measured preoperatively and up to 3 years postoperatively. Longitudinal changes were analyzed using Friedman's rank test. Primary endpoint was good general HRQOL based on QLQ-C30 global health status (GHS). Multivariate analysis was performed using logistic regression models with a step-wise backward selection procedure. RESULTS: Longitudinal analysis of HRQOL subdomains revealed significantly improved pain (p = .005) and fatigue (p = .002) scores as well as improved social functioning (p = .038). Furthermore, general HRQOL (GHS scores) improved significantly during the follow-up period (28.0 vs. 50.6 [36 months], p = .045). In multivariate analysis, the indication for salvage cystectomy could not be identified as an independent predictor for good general HRQOL. We observed a total number of 10 (41.7%) high-grade (Clavien ≥III) 90 day-complications. Limitations include limited follow-up rates at respective time-points. CONCLUSION: Salvage cystectomy and IC can be safely performed as a last-line treatment for benign conditions and increases general HRQOL in the long-term follow-up. Thus, it can play a role in a holistic approach for a challenging clinical setting.

Radical cystectomy for locally advanced urothelial carcinoma of the urinary bladder: Health-related quality of life, oncological outcomes and predictors for survival.

PURPOSE: While survival outcomes of locally advanced bladder cancer patients undergoing radical cystectomy are known to be poor, less is known regarding patient-reported outcomes and predictive features for survival in this patient subgroup. METHODS: One hundred and eighteen consecutive patients with pT4a cM0 urothelial carcinoma of the bladder were included. Based on pathological review, patients were stratified into 3 subgroups based on existence of additional lesions and invasion depth of the respective lesions. Cancer-specific survival and overall survival (OS) was determined using Kaplan-Meier-analyses and multivariate Cox regression models (P <0.05). Health-related quality of life was assessed using the validated EORTC-QLQ-C30 questionnaire pre- and postoperatively. RESULTS: Seventy-two (61.0%) patients were ineligible for neoadjuvant chemotherapy. Median follow-up based on censored patients was 12 months. Twelve month OS rate was 56.1%, 24 months OS rate was 21.1%. A total of 44.4% of the patients stated good general health-related quality of life. In multivariate analysis, we found significantly adverse OS outcomes for female patients (hazard ratio 2.35, 95% confidence interval 1.09-5.08, P = 0.030). Patients with at least 1 additional locally advanced tumor had significantly worse OS outcomes compared to patients who had no additional lesions in multivariate Cox regression analysis (hazard Ratio 3.37, 95% confidence interval 1.29-8.78, P = 0.013). CONCLUSION: Existence of multiple locally advanced lesions and female gender is an independent predictor of worse survival outcomes in patients with pT4a urothelial carcinoma undergoing radical cystectomy.

Preoperative Thrombocytosis in Patients Undergoing Radical Cystectomy for Urothelial Cancer of the Bladder: An Independent Prognostic Parameter for an Impaired Oncological Outcome.

BACKGROUND: Preoperative thrombocytosis (PTC) is frequently observed in various solid malignancies and often associated with an unfavourable oncological outcome. OBJECTIVES: The aim of this study was to investigate the influence of PTC in patients undergoing radical cystectomy (RC) for urothelial carcinoma (UC) of the bladder on the oncological prognosis and additionally on perioperative blood transfusions (PBT). METHOD: A retrospective analysis of 866 patients undergoing RC in a tertiary care centre was performed. PTC was defined as a platelet count >400 G/L. A chi-square test and Mann-Whitney test were used to investigate the association of PTC with categorical clinicopathological variables. A logrank test and multivariable Cox regression analyses were used to assess the association of PTC with cancer-specific survival. RESULTS: PTC was detected in 8% (n = 67) of the patients and was significantly associated with muscle invasion (p = 0.004), advanced tumour stages (p = 0.003) and nodal metastases (p < 0.001) and with a higher rate of PBT (p< 0.001). In the multivariate analysis, PTC was significantly related to poor oncological survival (hazard ratio 2.23, 95% CI 1.51-3.30, p < 0.001). CONCLUSION: PTC is significantly associated with an impaired oncological outcome in patients undergoing RC for UC. PTC therefore represents an independent and easy to determine prognostic parameter for patients' oncological outcome. Intriguingly, PTC is significantly associated with an increased rate of PBT.

Long-Term Follow-Up and Oncological Outcome of Patients Undergoing Radical Cystectomy for Bladder Cancer following an Enhanced Recovery after Surgery (ERAS) Protocol: Results of a Large Randomized, Prospective, Single-Center Study.

INTRODUCTION: Enhanced recovery after surgery (ERAS) concepts are implemented in various surgical disciplines. For patients undergoing radical cystectomy, prospective data are still rare. In the year 2014, our group could prove significant benefits of ERAS for these patients in a prospective randomized study compared to a conservative regimen. OBJECTIVE: To evaluate long-term follow-up results of ERAS concepts in patients undergoing radical cystectomy for bladder cancer. METHODS: Of the 101 patients who had initially prospectively been randomized to ERAS or a conservative regimen, 35 patients could be included in the study. Median follow-up time was 83 months. Primary end point assessed quality of life. Secondary end points were cancer-specific survival and overall survival. RESULTS: Five to seven years after the initial inclusion to the study, no significant difference regarding quality of life parameters was detected (p values range between 0.112 and 0.970). Continence status in patients with neobladder showed no significant differences between ERAS and conservative regimens (p = 0.785). Cancer-specific survival in the ERAS group did not differ significantly from that in the conservative group (49 vs. 58%, p = 0.725). CONCLUSIONS: While ERAS represents an excellent way to improve postoperative reconvalescence and quality of life in the short-term follow-up, our data do not support the idea that there is also a long-term effect in terms of quality of life issues.

Prognostic impact of perioperative blood transfusions on oncological outcomes of patients with bladder cancer undergoing radical cystectomy: A systematic review.

Objective: To conduct a systematic review of whether blood transfusions may be associated with worse outcomes for patients with bladder cancer treated with radical cystectomy (RC), as there has been a recent increase in studies addressing this clinically relevant topic. Methods: PubMed, Ovid Medical Literature Analysis and Retrieval System Online (MEDLINE), Google Scholar, and the ClinicalTrials.gov databases were searched with pre-specified search terms for studies published between January 2010 and May 2020. The systemic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: A total of 17 studies with 19 627 patients were included after 183 records were screened for eligibility. In all, 10 studies proposed perioperative blood transfusion to be associated with impaired prognosis regarding overall survival, nine studies regarding cancer-specific and four studies regarding recurrence-free survival. The timing of blood transfusion might affect patient outcomes. Notably, several studies did not find a significant correlation between blood transfusions and prognosis. As all studies to date are of retrospective design, the grade of evidence is still limited. Conclusions: Despite the lack of prospective trials, perioperative blood transfusion may lead to worse oncological outcomes. These results, as well as known non-oncological side-effects and associated costs, are important arguments to carefully consider the indication for blood transfusion. Abbreviations BCa: bladder cancer; CSS: cancer-specific survival; HR: hazard ratio; (N)MIBC: (non-) muscle-invasive BCa; OS: overall survival; PBT, perioperative blood transfusion; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; RC: radical cystectomy; RFS: recurrence-free survival.

Intravesical immunotherapy in nonmuscle invasive bladder cancer.

INTRODUCTION: Nonmuscle invasive urothelial cell carcinoma is the most frequent malignancy of the urinary bladder. The high recurrence rate (up to 80%) and risk of progression (up to 30%) reflect the need for long-term follow-up and sometimes multiple interventions. To reduce the rate of recurrences and tumor progression, intravesical immunotherapy, especially the use of Bacille Calmette-Guerin (BCG), represents the gold standard adjuvant treatment of high-risk nonmuscle invasive bladder cancer (NMIBC). This article reviews the role of BCG therapy and several promising new immunotherapeutic approaches such as mycobacterium phlei cell wall-nucleic acid complex, interleukin-10 (IL-10) antibody, vaccine-based therapy, alpha-emitter therapy, and photodynamic therapy checkpoint inhibitors. METHODS: A systematic literature review was performed using the terms (immunotherapy, NMIBC, BCG, and intravesical) using PubMed and Cochrane databases. RESULTS: BCG represents the most common intravesical immunotherapeutic agent for the adjuvant treatment of high-risk NMIBC. Its use is associated with a significant reduction of recurrence and progression. Patients with NMIBC of intermediate and high-risk benefit the most from BCG therapy. To achieve maximal efficacy, an induction therapy followed by a maintenance schedule should be used. Full-dose BCG is recommended to obtain ideal antitumoral activity and there is no evidence of a reduction of side effects in patients treated with a reduced dose. There are multiple new approaches and agents in immunotherapy with potential and promising antineoplastic effects. CONCLUSIONS: The beneficial effect of BCG is well documented and established. To reduce the tumor specific mortality, it is essential to follow guideline-based treatment. In patients with BCG-failure, there are new promising alternatives other than BCG but BCG remains the gold standard at this stage.