Robot-assisted laparoscopic radical cystectomy with intracorporeal ileal conduit diversion versus open radical cystectomy with ileal conduit for bladder cancer in an ERAS setup (BORARC): protocol for a single-centre, double-blinded, randomised feasibility study.

BACKGROUND: Radical cystectomy (RC) with urinary diversion is the recommended treatment for selected cases of non-metastatic high-risk non-muscle-invasive and muscle-invasive bladder cancer. It remains unknown whether robot-assisted laparoscopic cystectomy (RARC) offers any advantage in terms of safety compared to open cystectomy (ORC) in an Enhanced Recovery After Surgery (ERAS) setup. Blinded randomised controlled trials (RCTs) between RARC versus ORC have never been conducted in cystectomy patients. We will investigate the feasibility of conducting a double-blinded RCT comparing ORC with RARC with intra-corporal ileal conduit (iRARC) in an ERAS setup. METHODS: This is a single-centre, double-blinded, randomised (1:1) clinical feasibility study for patients with non-metastatic high-risk non-muscle-invasive or muscle-invasive bladder cancer scheduled for cystectomy. All participants are recruited from Rigshospitalet, Denmark. The planned sample size is 50 participants to investigate whether blinding of the surgical technique is feasible. Participants and postoperative caring physicians and nurses are blinded using a pre-study designed abdominal dressing and blinding of the patient's electronic health record. Study endpoints are assessed 90 days postoperatively. The primary aim is to study the frequency and pattern of unplanned unblinding after surgery and the number of participants who cannot guess the surgical technique at the day of discharge. Eleven secondary endpoints are assessed: length of stay, days alive and out of hospital, in-hospital complication rate, 30-day complication rate, 90-day complication rate, readmission rate, quality of life, blood loss, pain, rate of moderate/severe post-anaesthesia care unit (PACU) complications, and delirium. Participants are managed in an ERAS setup in both arms of the trial. DISCUSSION: We report on the design and objectives of a novel experimental feasibility study investigating whether blinding of the surgical technique in cystectomy patients is possible. This information is essential for the design of future blinded trials comparing ORC to RARC. There is a continued need to compare RARC and ORC in terms of both efficacy, safety, and oncological outcomes. Estimated end of study is March 2021. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03977831. Registered on the 6th of June 2019.

Quality of life and secondary outcomes for open versus robot-assisted radical cystectomy: a double-blinded, randomised feasibility trial.

PURPOSE: This study aims to examine quality of life (QoL) before and after radical cystectomy (RC) and compare robot-assisted laparoscopy with intracorporeal urinary diversion (iRARC) to open radical cystectomy (ORC). METHODS: This study is a predefined secondary analysis of a single-centre, double-blinded, randomised feasibility trial. Fifty patients were randomly assigned to iRARC with ileal conduit (n = 25) or ORC with ileal conduit (n = 25). Patients were followed 90 days postoperatively. The primary outcome was patient-reported QoL using the EORTC Cancer-30 and muscle-invasive bladder cancer BLM-30 QoL questionnaires before and after RC. Differences between randomisation arms as well as changes over time were evaluated. Secondary outcomes included 30- and 90 day complication rates, 90 day readmission rates, and 90 day days-alive-and-out-of-hospital and their relationship to QoL. RESULTS: All patients underwent the allocated treatment. We found no difference in QoL, complication rates, readmission rates, and days-alive-and-out-of-hospital between randomisation arms. An overall improvement in QoL was found in the following domains: future perspectives, emotional functioning, and social functioning. Sexual functioning worsened postoperatively. There was no association between having experienced a major complication or lengthy hospitalisation and worse postoperative QoL. CONCLUSION: The QoL does not appear to depend on surgical technique. Apart from sexual functioning, patients report stable or improved QoL within the first 90 postoperative days.

Risk of recurrence and long-term mortality following radical cystectomy for bladder cancer.

PURPOSE: To investigate the risk of recurrence and long-term mortality after radical cystectomy (RC) for bladder cancer (BC) at a high-volume tertiary referral center in Denmark over 19 years. MATERIALS AND METHODS: Patients undergoing RC between the 1st of January 2000 to 31st of December 2018 were included. Patient data were manually retrieved from electronic patient files. Follow-up ended 18th of May 2020. Cumulative incidences were used to assess risk of recurrence and mortality using competing risk modelling. Cause-specific Cox regression models were used for multivariable analysis. RESULTS: A total of 1267 patients underwent RC of which 1042 were eligible for analysis. Overall mortality was 40% and 56% after 5 and 10 years, respectively. The cumulative incidence of recurrence and BC specific mortality was high within the first 2 years. Only 3.2% of the patients with recurrence were alive at the end of follow-up. The cumulative incidence of BC mortality after 5 years was 6.7% (95% CI 3.6-9.9) and 10% (95% CI 6.8-14) for patients with ≤ pT1bN0 and pT2N0, respectively. For patients with lymph node positive disease the cumulative incidence of BC mortality after 5 years was 65% (95% CI 58-71). CONCLUSIONS: We found a significant risk of recurrence and disease-specific mortality following RC for BC, especially within the first 2 years following surgery. Our data seem comparable to other large cohorts. The chance of long-term survival following recurrence is low and there is a continuous need to improve adjuvant or salvage strategies following RC.

Reasons why not all Danish patients with muscle invasive bladder cancer receive neoadjuvant chemotherapy before radical cystectomy.

Background: Danish guidelines on muscle invasive bladder cancer (MIBC) recommend neoadjuvant chemotherapy (NAC) for non-metastatic patients fit for cisplatin-based chemotherapy. The current indication is urothelial MIBC in patients less than 75 years old with no metastasis on imaging and normal renal function (GFR ≥ 60 ml/min). Data from the Danish Bladder Cancer Database (DaBlaCa-Data) reveals that only 40-50% of MIBC patients below 75 years of age receive NAC prior to cystectomy. The aim of this study was to clarify the reasons why the remaining patients do not receive NAC.Methods: Individual patient data were collected retrospectively from all five Danish urologic departments performing cystectomies. Patients fulfilling the inclusion criteria: MIBC at TURBT, age less than 75 years old and subsequent cystectomy were included and registered by the specific reason why NAC was not given. In total, 449 patients met the age- and T-stage criteria for NAC in the period September 2014 through August 2017.Results: In total, 274 patients (61.0%) received chemotherapy. Of the 175 patients who did not receive NAC, 140 patients (80%) were not fit for cisplatin and 35 patients did not receive NAC and had no specific contraindication. This ranged from 0-18% of included patients in the different centres. The main reason was patient refusal (97%). Interestingly, this ranged from 0-50% of patients not receiving NAC when comparing the five centres.Conclusion: These findings underline the need for proper patient information in order to get a uniform treatment strategy between centres.

Human papillomavirus and squamous cell carcinoma of the urinary bladder: DaBlaCa-10 study.

OBJECTIVE: To evaluate a potential association between Human Papillomavirus (H.P.V.) and squamous cell carcinoma (S.C.C.) urinary bladder cancer (B.C.). Furthermore, the relation between p16INK4a, H.P.V. and B.C. was examined. PATIENTS AND METHODS: Patients were included and divided into three groups based on the histological diagnosis of B.C. SPECIMENS: An extensive exclusion was performed, including accepted casual risk factors for S.C.C. B.C., such as long-term use of catheters, cystolithiasis and Schistosoma hematobium infection. A total of 100 patients were included: 50 with pure S.C.C., 25 with urothelial carcinomas (U.C.) and 25 with squamous differentiation of U.C. (Sq.D.). The patients were operated at one of four major Danish hospitals in the period January 2005 to December 2016. Clinical information was collected from the medical records. Presence of H.P.V. was analyzed using the INNO-LiPA H.P.V. Genotyping Extra II. p16INK4a was analyzed using immunohistochemical (I.H.C.) staining. A p-value <0.05 was considered statistically significant. RESULTS: An overall H.P.V. prevalence of 12/100 (12%) was observed. H.P.V. was demonstrated in 9/50 (18%) of the S.C.C. PATIENTS: Overall, p16INK4a over-expression was observed in 52/100 (52%) patients. However, concomitant H.P.V. positivity and p16INK4a over-expression were observed in only 4/100 (4%) patients. CONCLUSION: The presence of H.P.V. in one fifth of patients with S.C.C. B.C. was demonstrated. H.P.V. infection could have a significant association with S.C.C. B.C. without other known casual risk factors for S.C.C. B.C.