Prognostic impact of variant histologies in urothelial bladder cancer treated with radical cystectomy.

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.

Clinical outcomes of adapted hypofractionated radiotherapy for bladder cancer in elderly patients.

OBJECTIVE: To investigate the feasibility, efficacy, and safety of trimodal therapy (TMT) using a bifractionated split-course hypofractionated radiotherapy (RT) for non-metastatic muscle-invasive bladder cancer (MIBC) in elderly patients. PATIENTS AND METHODS: We retrospectively reviewed the characteristics and outcomes of patients aged >75 years with non-metastatic MIBC suitable or not for radical cystectomy (RC) and treated with transurethral resection of bladder tumour followed by concomitant radio-chemotherapy (platinum salt and 5-fluorouracil) at two institutions (Saint Louis Hospital, Paris, France and European Georges Pompidou Hospital, Paris, France) between 1990 and 2021. RT consisted of an adapted bifractionated split-course hypofractionated RT. Acute toxicities were reported according to Common Terminology Criteria for Adverse Events version 5.0 and late toxicities were reported according to the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer late radiation morbidity scoring schema. The primary end-point was overall survival (OS). Secondary end-points included other survivals outcomes and safety. RESULTS: A total of 122 patients were identified, with a median (range) follow-up of 51.1 (0.5-210.8) months. In all, 83.5% of patients completed radio-chemotherapy. The OS rate was 61.7% at 3 years and 51.2% at 5 years. In multivariate analysis, the completion of RT and concomitant chemotherapy were significantly associated with better OS and cancer-specific survival. For patients fit for RC, a complete histological response was achieved for 77 patients (91.7%) with radio-chemotherapy and the bladder conservation rate was 90.5%. Acute and late Grade ≥3 toxicities were <5%. CONCLUSION: Bifractionated split-course hypofractionated RT with concomitant chemotherapy regimen appears to be well-tolerated and effective. Trimodal treatment seems to be a curative option for elderly patients unfit for radical surgery compared with palliative care and may contribute to improved survival in these patients.

Oncological and safety profiles in patients undergoing simultaneous transurethral resection (TUR) of bladder tumour and TUR of the prostate.

OBJECTIVES: To determine the oncological impact and adverse events of performing simultaneous transurethral resection of bladder tumour (TURB) and transurethral resection of the prostate (TURP), as evidence on the outcomes of simultaneous TURB for bladder cancer and TURP for obstructive benign prostatic hyperplasia is limited and contradictory. PATIENTS AND METHODS: Patients from 12 European hospitals treated with either TURB alone or simultaneous TURB and TURP (TURB+TURP) were retrospectively analysed. A propensity score matching (PSM) 1:1 was performed with patients from the TURB+TURP group matched to TURB-alone patients. Associations between surgery approach with recurrence-free (RFS) and progression-free (PFS) survivals were assessed in Cox regression models before and after PSM. We performed a subgroup analysis in patients with risk factors for recurrence (multifocality and/or tumour size >3 cm). RESULTS: A total of 762 men were included, among whom, 76% (581) underwent a TURB alone and 24% (181) a TURB+TURP. There was no difference in terms of tumour characteristics between the groups. We observed comparable length of stay as well as complication rates including major complications (Clavien-Dindo Grade ≥III) for the TURB-alone vs TURB+TURP groups, while the latest led to longer operative time (P < 0.001). During a median follow-up of 44 months, there were more recurrences in the TURB-alone (47%) compared to the TURB+TURP group (28%; P < 0.001). Interestingly, there were more recurrences at the bladder neck/prostatic fossa in the TURB-alone group (55% vs 3%, P < 0.001). TURB+TURP procedures were associated with improved RFS (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.29-0.53; P < 0.001), but not PFS (HR 1.63, 95% CI 0.90-2.98; P = 0.11). Within the PSM cohort of 254 patients, the simultaneous TURB+TURP was still associated with improved RFS (HR 0.33, 95% CI 0.22-0.49; P < 0.001). This was also true in the subgroup of 380 patients with recurrence risk factors (HR 0.41, 95% CI 0.28-0.62; P < 0.001). CONCLUSION: In our contemporary cohort, simultaneous TURB and TURP seems to be an oncologically safe option that may, even, improve RFS by potentially preventing disease recurrence at the bladder neck and in the prostatic fossa.

Oncological impact of cystoscopic findings in non-muscle-invasive bladder cancer: a meta-analysis.

OBJECTIVE: To assess the association between cystoscopic findings and oncological outcomes in patients with non-muscle-invasive bladder cancer (NMIBC) given that the oncological impact of quantity and quality assessment of tumours with cystoscopy has not been well verified. METHODS: Multiple databases were queried in May 2022 for studies investigating the association of oncological outcomes, such as recurrence-free (RFS), progression-free (PFS), and cancer-specific survival (CSS), with cystoscopic findings, including multiplicity, size, and gross appearance of tumours in patients with NMIBC. RESULTS: Overall, 73 studies comprising 28 139 patients were eligible for the meta-analysis. Tumour multiplicity was associated with worse RFS (pooled hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.48-1.74) and PFS (pooled HR 1.44, 95% CI 1.18-1.76) in NMIBC patients (including both Ta and T1). Tumour size (≥3 cm) was associated with worse RFS (pooled HR 1.97, 95% CI 1.69-2.30) and PFS (pooled HR 1.81, 95% CI 1.52-2.15) in NMIBC patients. In patients with T1 bladder cancer (BCa), tumour multiplicity and size (≥3 cm) were also associated with worse RFS, PFS and CSS. By contrast, among patients treated with bacillus Calmette-Guérin (BCG), tumour multiplicity was not associated with worse RFS, and tumour size (≥3 cm) was not associated with worse PFS. Sessile tumours were associated with worse RFS (pooled HR 2.14, 95% CI 1.52-3.01) and PFS (pooled HR 2.17, 95% CI 1.42-3.32) compared to pedunculated tumours. Compared to papillary tumours, solid tumours were associated with worse RFS (pooled HR 1.84, 95% CI 1.25-2.72) and PFS (pooled HR 3.06, 95% CI 2.31-4.07) in NMIBC patients, and CSS in T1 BCa patients (pooled HR 2.32, 95% CI 1.63-3.30). CONCLUSIONS: Cystoscopic findings, including tumour multiplicity, size, and gross appearance, strongly predict oncological outcomes in NMIBC patients. Cystoscopic visual features can help in the decision-making process regarding the timeliness and extent of tumour resection as well as future management such as intravesical therapy.

Clinical presentation of bacille Calmette-Guérin (BCG) infections after BCG instillation therapy.

OBJECTIVES: To investigate the timing of the clinical presentation of various types of bacille Calmette-Guérin (BCG) infections in a Finnish population of patients with bladder cancer treated with BCG instillation therapy. PATIENTS AND METHODS: We identified patients with a history of post-instillation BCG infection from 1996 to 2016 using the Finnish Cancer Registry and the Finnish National Infectious Diseases Registry. We categorised infections as systemic if the infection was found in the non-urogenital system and genitourinary (GU) if the infection affected the urogenital tract. We calculated the time interval between the last BCG instillation and the presentation of the infection. The infection was considered late if the time interval was ≥1 year. RESULTS: A total of 100 patients with BCG infection were identified during the study period. In all, 39 (39%) infections presented as systemic and 61 (61%) were in the GU tract. The majority of the systemic infections presented rapidly after the last instillation, while five (13%) presented after a latency of ≥1 year. The presentation of GU infections was more heterogeneous, with 12 (20%) presenting as late infections. CONCLUSION: This study confirms the concept of early and late infection types, especially among systemic infections. However, late infections appeared to be rarer than previously described. Urologists should be aware of the possibility of late BCG infection if patients develop symptoms even several years after the BCG regimen.

Oncological validation and discriminative ability of pentafecta criteria after open radical cystectomy.

OBJECTIVES: To validate the pentafecta criteria (PC) proposed by the PROMETRICS group for outcome reporting after radical cystectomy in an open radical cystectomy (ORC) cohort with long-term follow-up and to assess the discriminative ability of PC attainment for oncological endpoints. PATIENTS AND METHODS: Between January 2009 and December 2017, 420 patients underwent ORC with pelvic lymph node dissection and urinary diversion for non-metastatic bladder cancer. The PC were defined as reported by the PROMETRICS group. The primary endpoint was PC attainment, and oncological outcomes comprised further endpoints. We used uni- and multivariable logistic regression analysis to assess predictors of PC attainment. The discriminative ability of PC for overall mortality (OM), cancer-specific mortality (CSM) and other-cause mortality (OCM) was compared using Kaplan-Meier curves and cumulative incidence functions. After stratification by the number of PC attained, the association between PC attainment and the survival endpoints was tested on multivariable Cox regression and competing-risks models. RESULTS: A total of 108 patients (26%) fulfilled all PC, while 195 (46%), 77 (18%), 35 (8.3%) and five (1.2%) attained 4/5, 3/5, 2/5 and ≤1/5 PC, respectively. Increasing age-adjusted Charlson comorbidity index (odds ratio [OR] 0.80, P = 0.015) and incontinent diversion (OR 0.38, P = 0.005) were independent predictors of PC non-attainment. The median follow-up was 73 months. PC attainment (≥4/5 vs 3/5 vs ≤2/5 PC attained) was used to stratify patients into groups at significantly different risk of death (P < 0.001). A decreasing number of PC attained (<4/5) was associated with unfavourable survival estimates for both OM and CSM (all P ≤ 0.005) but not for OCM (all P ≥ 0.2). CONCLUSIONS: The PC proposed by the PROMETRICS group represent accurate quality indicators for oncological outcome reporting after ORC for non-metastatic bladder cancer and have a distinct discriminative ability to predict long-term OM and CSM.

The influence of multidisciplinary team meetings on treatment decisions in advanced bladder cancer.

OBJECTIVES: To investigate the role of specialised genitourinary multidisciplinary team meetings (MDTMs) in decision-making and identify factors that influence the probability of receiving a treatment plan with curative intent for patients with muscle invasive bladder cancer (MIBC). PATIENTS AND METHODS: Data relating to patients with cT2-4aN0/X-1 M0 urothelial cell carcinoma, diagnosed between November 2017 and October 2019, were selected from the nationwide, population-based Netherlands Cancer Registry ('BlaZIB study'). Curative treatment options were defined as radical cystectomy (RC) with or without neoadjuvant chemotherapy, chemoradiation or brachytherapy. Multilevel logistic regression analyses were used to examine the association between MDTM factors and curative treatment advice and how this advice was followed. RESULTS: Of the 2321 patients, 2048 (88.2%) were discussed in a genitourinary MDTM. Advanced age (>80 years) and poorer World Health Organization performance status (score 1-2 vs 0) were associated with no discussion (P < 0.001). Being discussed was associated with undergoing treatment with curative intent (odds ratio [OR] 3.0, 95% confidence interval [CI] 1.9-4.9), as was the involvement of a RC hospital (OR 1.70, 95% CI 1.09-2.65). Involvement of an academic centre was associated with higher rates of bladder-sparing treatment (OR 2.05, 95% CI 1.31-3.21). Patient preference was the main reason for non-adherence to treatment advice. CONCLUSIONS: For patients with MIBC, the probability of being discussed in a MDTM was associated with age, performance status and receiving treatment with curative intent, especially if a representative of a RC hospital was present. Future studies should focus on the impact of MDTM advice on survival data.

Surgical checklist adherence across urology expertise levels impacts transurethral resection of bladder tumour quality indicators.

OBJECTIVES: To address the association of perioperative surgical checklist across variable surgical expertise with transurethral resection of bladder tumour (TURBT) accuracy and oncological outcomes in non-muscle-invasive bladder cancer. PATIENTS AND METHODS: We relied on our prospective collaborative database of patients treated with TURBT between 2012 and 2017. Surgical experience was stratified into three groups: resident vs young vs expert consultants. The association of surgical experience with detrusor muscle (DM) presence and adherence to the standardised peri-procedural nine-items TURBT checklist was evaluated with logistic regression models. A Cox regression model was used to investigate the association of surgical experience with recurrence-free survival (RFS). RESULTS: A total of 503 patients were available for analysis. TURBT was performed by expert consultants in 265 (52.7%) patients, by young consultants in 149 (29.6%) and by residents in 89 (17.7%). Residents were more likely to have DM in the TURBT specimen than expert consultants (odds ratio [OR] 1.75, 95% confidence interval [CI] 1.03-2.99, P = 0.04). Conversely, no differences in DM presence were seen between young vs expert consultants (OR 1.09, 95% CI 0.71-1.70, P = 0.69). The median checklist completion rate was higher for both residents and young consultants when compared to experts' counterparts (56% and 56% vs 44%, P = 0.009). When focusing on patients receiving a second-look TURBT, the persistent disease was associated with resident status (OR 4.24, 95% CI 1.14-17.70, P = 0.037) at initial TURBT. Surgical experience was not associated with 5-years RFS. CONCLUSION: Surgeon's experience in the case of adequate perioperative surgical checklist implementation was inversely associated with the presence of DM in the specimen but directly linked to higher probability of persistent disease at re-TURBT, although no 5-year RFS differences were noted.

Robotic Radical Cystectomy with Intracorporeal Urinary Diversion - Tips and Tricks.

Radical cystectomy represents the standard surgical treatment in case of muscle invasive bladder cancer. During the last two decades a change in the surgical approach of the MIBC has been observed, from open surgery to minimal invasive surgery. Nowadays, in the majority of tertiary urologic centers, robotic radical cystectomy with intracorporeal urinary diversion represents the standard surgical approach. The aim of the current study is to describe in detail the surgical steps of the robotic radical cystectomy and the reconstruction of the urinary diversion and to present our experience. From the surgical point of view, the most important principles which should guide the surgeon when performing this procedure are: 1. Good working place and access both to the pelvis and abdomen and use of the "technique of spaces" 2. Respect the oncological principles of the surgery with attention to the margin resection and limitation of the risk of tumour spillage; 3. Attention to both the ureter and bowel manipulation in order to avoid grasping lesions; 4. High care in realisation of the uretero-ileal anastomosis so that good long term functional results are achieved. We analyzed our database of 213 patients diagnosed with muscle invasive bladder cancer who underwent minimally invasive radical cystectomy (laparoscopic and robotic approaches) between January 2010 and December 2022. We identified 25 patients for whom the robotic approach was used to perform the surgery. Despite being one of the most challenging urologic surgical procedures, with careful preparation and training, the surgeon is able to achieve the maximum oncological and functional results by performing robotic radical cystectomy with intracorporeal urinary.

Uretero-enteric stricture outcomes: secondary analysis of a randomised controlled trial comparing open versus robot-assisted radical cystectomy.

OBJECTIVES: To analyse the risk of uretero-enteric anastomotic stricture in patients randomised to open (ORC) or robot-assisted radical cystectomy (RARC) with extracorporeal urinary diversion. PATIENTS AND METHODS: We included 118 patients randomised to RARC (n = 60) or ORC (n = 58) at a single, high-volume institution from March 2010 to April 2013. Urinary diversion was performed by experienced open surgeons. Stricture was defined as non-malignant obstruction on imaging, corroborated by clinical status, and requiring procedural intervention. The risk of stricture within 1 year was compared between groups using Fisher's exact test. RESULTS: In all, 58 and 60 patients were randomised to RARC and ORC, respectively. We identified five strictures, all in the ORC group. In patients with ≥1 year of follow-up, the increase in risk of stricture from open surgery was 9.3% (95% confidence interval 1.5%, 17%). Of the five strictures, three were managed endoscopically while two required open revision. There was no evidence that perioperative Grade 3-5 complications were associated with development of a stricture (P = 1) and no evidence of a difference in 24-month estimated glomerular filtration rate between arms (P = 0.15). CONCLUSIONS: In this study at a high-volume centre, RARC with extracorporeal urinary diversion achieved excellent ureteric anastomotic outcomes. Purported increased risk of stricture is not a reason to avoid RARC. Future research should examine the impact of different surgical techniques and operator experience on the risk of stricture, especially as more intracorporeal diversions are performed.

The development of the Cystectomy-Pathway Assessment Tool (C-PAT): a concise tool to assess the quality of care in the cystectomy pathway.

OBJECTIVES: To develop and test the psychometric properties of a concise, patient-reported questionnaire, designed to assess key aspects of the radical cystectomy (RC) patient pathway that are important to both patients and clinicians. PATIENTS AND METHODS: Draft items were developed by a consultation with a 13-member expert clinical panel, and the in-depth qualitative analysis of 14 semi-structured interviews with patients who had received RC within the previous 18 months. A further nine cognitive interviews with patients refined the items and ensured they were easy to complete. Pilot testing in 122 patients recruited from five hospitals in England tested the properties of validity and reliability of the resulting 17-item questionnaire. RESULTS: Patients and clinicians identified the following aspects as important for the delivery of quality patient care. These included timely referral and initial test results; an explanation of risk/benefits of treatment; access to a cancer nurse specialist; training and support in stoma management; timely surgery, surgical complications, and timely follow-up. Pilot testing showed missing data was low (≤3% for all items), and between 73% and 89% of the responses to items were the most positive about their care (indicating ceiling effects). Five items were identified using factor analysis as being statistically related (Cronbach's α 0.76, intraclass correlation coefficient test-retest reliability of 0.95) and formed the scored part of the tool 'care and support', scored 0-16. There was insufficient evidence at this stage to show the tool was capable of measuring differences between cancer centres. CONCLUSION: We have developed a questionnaire that captures aspects of quality of care within the RC patient pathway. The results support the validity and reliability of the 17-item Cystectomy-Pathway Assessment Tool (C-PAT). We envisage the tool can be the basis for audit of the patient reported assessment of the quality of care for individual cancer centres.

Long-term renal function in patients with chronic kidney disease following radical cystectomy and orthotopic neobladder.

OBJECTIVE: To evaluate long-term renal function in patients with chronic kidney disease (CKD) Stage IIIa who underwent radical cystectomy and orthotopic neobladder (RC/ONB) compared to matched controls. PATIENTS AND METHODS: Using our Institutional Review Board-approved institutional database, patients with a glomerular filtration rate (GFR) of 45-59.9 mL/min/1.73 m2 who underwent RC/ONB were identified. A control group of patients with a GFR of ≥60 mL/min/1.73 m2 was selected. Groups were matched based on age, baseline hypertension/diabetes mellitus, perioperative chemotherapy, and preoperative hydronephrosis. A decrease in GFR of >10 mL/min/1.73 m2 during the follow-up was considered significant. A multivariate Cox regression analysis was performed to identify predictors of GFR decline in each group. RESULTS: Of 1237 patients who underwent RC/ONB, 508 patients were included (254 per group). The mean preoperative GFR was 53.3 mL/min/1.73 m2 in the study group and 78.8 mL/min/1.73 m2 in controls. The median follow-up was 3.7 years. During follow-up, GFR stayed at or above baseline in 51% of the study patients compared to 46% of the controls (P = 0.5). The mean time to a significant GFR decline in the study patients was significantly longer compared to the controls (5.6 vs 2 years, respectively; P < 0.001). In multivariate analysis, neoadjuvant chemotherapy was found to be the strongest predictor of a significant GFR decline as well as GFR decline below baseline (hazard ratio [HR] 2.15, 95% confidence interval [CI] 1.4-3.29, P = 0.004; and HR 2.15, 95% CI 1.4-3.29, P < 0.001, respectively). CONCLUSION: Patients with CKD Stage IIIa who undergo ONB appear to have comparable long-term renal function to those with a GFR of ≥60 mL/min/1.73 m2 . An ONB reconstruction is a safe option for patients with CKD Stage IIIa desiring a continent diversion.

Association between early change in neutrophil-to-lymphocyte ratio after radical cystectomy and treatment outcomes.

OBJECTIVES: To evaluate the associations of peri-operative neutrophil-to-lymphocyte ratio (NLR) and change in NLR with survival after radical cystectomy. PATIENTS AND METHODS: We retrospectively reviewed a multicentre cohort of patients with bladder cancer who underwent radical cystectomy between 2010 and 2020. Preoperative NLR, postoperative NLR, delta-NLR (postoperative minus preoperative NLR) and NLR change (postoperative divided by preoperative NLR) were calculated. Patients were stratified based on elevation of preoperative and/ or postoperative NLR above the median values. Multivariable Cox regression models were used to evaluate the associations of peri-operative NLR and NLR change with survival. RESULTS: The study cohort included 346 patients with a median age of 69 years. The median (interquartile range) preoperative NLR, postoperative NLR, delta-NLR and NLR change were 2.55 (1.83, 3.90), 3.33 (2.21, 5.20), 0.43 (-0.50, 2.08) and 1.2 (0.82, 1.96), respectively. Both preoperative and postoperative NLR were elevated in 110 patients (32%), 126 patients (36%) had an elevated preoperative or postoperative NLR, and 110 patients (32%) did not have an elevated NLR. On multivariable analysis, increased preoperative and postoperative NLR were significantly associated with decreased survival. While delta-NLR and NLR change were not associated with outcome, patients with elevations in both preoperative and postoperative NLR had the worst overall (hazard ratio [HR] 2.97, 95% confidence interval [CI] 1.78, 4.95; P < 0.001) and cancer-specific survival rates (HR 2.41, 95% CI 1.3, 4.4; P = 0.004). CONCLUSIONS: Preoperative and postoperative NLR are significant predictors of survival after radical cystectomy; patients in whom both NLR measures were elevated had the worst outcomes. Future studies should evaluate whether an increase in NLR during long-term follow-up may precede disease recurrence.

Perioperative continuation of aspirin, oral anticoagulants or bridging with therapeutic low-molecular-weight heparin does not increase intraoperative blood loss and blood transfusion rate in cystectomy patients: an observational cohort study.

OBJECTIVE: To assess if uninterrupted anticoagulant agents' administration affects blood loss and blood transfusion during open radical cystectomy (RC) and urinary diversion. PATIENTS AND METHODS: We conducted an observational single-centre cohort study of a consecutive series of 1430 RC patients, between 2000 and 2020. Blood loss was depicted according to body weight and duration of surgery (mL/kg/h), and blood transfusion. The group 'with anticoagulant agents' was considered if surgery was performed with uninterrupted low-dose aspirin (ASS), oral anticoagulants (OAC) with an international normalised ratio (INR) goal of 2-2.5 or bridging with therapeutic low-molecular-weight heparin (LMWH). Outcomes were intraoperative blood loss, blood transfusion rate (separately analysed if administered within 24 h perioperatively or >24 h after surgery) and the 90-day major adverse cardiac events (MACE) rate. We used propensity score (PS)-matching analysis to adjust for imbalances between groups with or without anticoagulant agents. RESULTS: The PS-matched median (interquartile range [IQR]) blood loss was 2.10 (1.50-2.94) mL/kg/h in patients with anticoagulant agents vs 2.11 (1.47-2.94) mL/kg/h without anticoagulant agents (Padj > 0.99). The PS-matched blood transfusion rates were 26.2% vs 35.1% (Padj = 0.875) within 24 h perioperatively and 57.0% vs 55.0% (Padj = 0.680) if administered >24 h postoperatively. A sub-analysis of the three different anticoagulant agents could not detect any significance between ASS, OAC, or LMWH. The PS-matched incidence of MACE was 9.1% in the group with anticoagulant agents and 8.1% in those without anticoagulant agents (Padj > 0.99). Limitations include selection bias and retrospective analysis from prospectively assessed data. CONCLUSIONS: Perioperative continuation of ASS, uninterrupted OAC with low INR goal or bridging with LMWH had no impact on blood loss and transfusion rate in RC patients. Therefore, there might be no compulsory need for discontinuation of anticoagulant agents.

Safety of neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer and malignant ureteric obstruction.

OBJECTIVES: To determine whether patients with carcinoma invading bladder muscle (MIBC) and ureteric obstruction can safely receive cisplatin-based neoadjuvant chemotherapy (C-NAC), and to determine whether such patients require relief of obstruction with a ureteric stent or percutaneous nephrostomy prior to beginning C-NAC. PATIENTS AND METHODS: We performed a single-institution retrospective analysis of MIBC patients receiving C-NAC and falling into three groups: no ureteric obstruction (NO); relieved ureteric obstruction (RO); and unrelieved ureteric obstruction (URO). To address whether patients with obstruction can safely receive C-NAC, we compared patients with NO to those with RO, with the primary outcome of premature chemotherapy discontinuation. To investigate whether patients with obstruction should have the obstruction relieved prior to NAC, we compared RO to URO patients using a primary composite outcome of grade ≥ 3 adverse events, premature chemotherapy discontinuation, dose reduction, or dose interruption. The primary outcomes were compared using multivariable logistic regression. Sensitivity analyses were performed for the RO vs URO comparison, in which patients with only mild degrees of obstruction were excluded from the URO group. RESULTS: A total of 193 patients with NO, 49 with RO, and 35 with URO were analysed. There were no statistically significant differences between those with NO and those with RO in chemotherapy discontinuation (15% vs 22%; P = 0.3) or any secondary outcome. There was no statistically significant difference between those with RO and URO in the primary composite outcome (51% vs 53%; P = 1) or any secondary outcome. CONCLUSION: Patients with ureteric obstruction can safely receive C-NAC. Relief of obstruction was not associated with increased safety of C-NAC delivery.

Artificial intelligence to improve cytology performances in bladder carcinoma detection: results of the VisioCyt test.

OBJECTIVE: To explore the utility of artificial intelligence (AI) using the VisioCyt® test (VitaDX International, Rennes, France) to improve diagnosis of bladder carcinoma using voided urine cytology. PATIENTS AND METHODS: A national prospective multicentre trial (14 centres) was conducted on 1360 patients, divided in two groups. The first group included bladder carcinoma diagnosis with different histological grades and stages, and the second group included control patients based on negative cystoscopy and cytology results. The first step of this VISIOCYT1 trial focussed on algorithm development and the second step on validating this algorithm. A total of 598 patients were included in this first step, 449 patients with bladder tumours (219 high-grade and 230 low-grade) and 149 as negative controls. The VisioCyt test was compared to voided urine cytology performed by experienced uro-pathologists from each centre. RESULTS: Overall sensitivity was highly improved by the VisioCyt test compared to cytology (84.9% vs 43%). For high-grade tumours the VisioCyt test sensitivity was 92.6% vs 61.1% for the uro-pathologists. Regarding low-grade tumours, VisioCyt test sensitivity was 77% vs 26.3% for the uro-pathologists. CONCLUSION: In comparison to routine cytology, the results of the first phase of the VISIOCYT1 trial show very clear progress in terms of sensitivity, which is particularly visible and interesting for low-grade tumours. If the validation cohort confirms these results, it could lead to the VisioCyt test being considered as a very useful aid for pathologists. Moreover, as this test is in fact software based on AI, it should become more and more efficient as more data are collected.

Clinical efficacy of mebeverine for persistent nocturnal enuresis after orthotopic W-neobladder.

OBJECTIVES: To investigate the efficacy of mebeverine for nocturnal incontinence in male patients with an ileal orthotopic bladder substitute (OBS). PATIENTS AND METHODS: A randomised controlled trial was carried out for adult male patients who were nocturnal incontinent. Patients were allocated to receive mebeverine 200 mg or placebo once a day in the evening for 3 months. The primary outcome was to compare the continence status between groups, assessed by the urinary domain of the Bladder Cancer Index (BCI) and pad usage. The secondary outcomes were to assess the safety of mebeverine. RESULTS: There were 55 patients in the placebo group and 58 in mebeverine group who completed the follow-up. The median (interquartile range) interval between OBS surgery and starting treatment was 9 (4-13) years in the placebo group and 9 (6-13) years in the mebeverine group. The mean (SD) 3-month urinary domain score of the BCI was 70.8 (5.6) and 86.4 (14.2) in the placebo and mebeverine groups, respectively (P < 0.001). At 3 months, 54 (98.2%) and 26 (44.8%) patients required the use of a night-time pad in the placebo and mebeverine groups, respectively. Mebeverine reduced the risk of pad use by 53.4% (95% confidence interval 40.1-66.6; P < 0.001). Constipation occurred in one (2.1%) and three (5.8%) patients in the placebo and mebeverine groups, respectively; abdominal distention occurred in two (3.8%) of the patients in the mebeverine group (P = 0.25). CONCLUSION: Mebeverine decreases night-time pad use and improves the quality of life in male patients with an ileal OBS and is associated with minimal adverse events.

Recovery of health-related quality of life in patients undergoing robot-assisted radical cystectomy with intracorporeal diversion.

OBJECTIVE: To report the health-related quality of life (HRQoL) after robot-assisted radical cystectomy and intracorporeal urinary diversion (iRARC), and to identify factors impacting on return to baseline. PATIENTS AND METHODS: Consecutive patients undergoing iRARC between January 2016 and December 2017 completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30-item core (EORTC-QLQ-C30) and EORTC-QLQ-Muscle-Invasive Bladder Cancer Module (EORTC-QLQ-BLM30) questionnaires before surgery and had a minimum of 12 months follow-up postoperatively. RESULTS: A total of 76 patients met the inclusion criteria at 12 months. Neobladder (NB) cases (n = 24) were younger (57.0 vs 71.0 years, P < 0.001) and fitter than ileal conduit (IC) cases (n = 52), and had higher physical (100.0 vs 93.3, P = 0.039) and sexual functioning (66.7 vs 50.0, P = 0.013) scores at baseline. Longitudinal analysis of the EORTC-QLQ-C30 showed that physical (NB: 93.3 vs 100.0, P = 0.020; IC: 80.0 vs 93.3, P < 0.001) and role functioning scores (NB: 83.3 vs 100.0, P = 0.010; IC: 83.3 vs 100.0, P = 0.017) decreased and fatigue score (NB: 22.2 vs 11.1, P = 0.026; IC: 33.3 vs 22.2, P = 0.008) increased at 3 months in both diversion groups. Scores returned to baseline at 6 months except physical functioning score in IC patients that remained below baseline until 12 months (86.7 vs 93.3, P = 0.012). The global HRQoL score did not show significant change postoperatively in both groups. A major 90-day Clavien-Dindo complication was a significant predictor (odds ratio [OR] 0.11, 95% confidence interval [CI] 0.02-0.62; P = 0.012) of deteriorated global HRQoL score at 3 months, while occurrence of a late complication (OR 0.14, 95% CI 0.03-0.65; P = 0.013) was a predictor of deteriorated global HRQoL score at 12 months. Longitudinal analysis of the EORTC-QLQ-BLM30 showed that urinary problems (NB: 14.3 vs 38.3, P < 0.001; IC: 5.6 vs 19.1, P < 0.001) and future perspective (NB: 33.3 vs 44.4, P = 0.004; IC: 22.2 vs 44.4, P < 0.001) scores were better than baseline at 3 months. Sexual function deteriorated significantly at 3 months (NB: 8.3 vs 66.7, P < 0.001; IC: 4.2 vs 50.0, P < 0.001) and then showed improvement at 12 months but was still below baseline (NB: 33.3 vs 66.7, P = 0.001; IC: 25.0 vs 50.0, P < 0.001). Involvement in penile rehabilitation was shown to be a significant predictor (ß 18.62, 95% CI 6.06-30.45; P = 0.005) of higher sexual function score at 12 months. CONCLUSION: While most functional domains and symptoms scales recover to or exceed baseline within 6 months of iRARC, physical function remains below baseline in IC patients up to 12 months. Global HRQoL is preserved for both types of urinary diversion; however, postoperative complications seem to be the main driving factor for global HRQoL. Sexual function is adversely affected after iRARC suggesting that structured rehabilitation of sexual function should be an integral part of the RC pathway.

Incidence of and mortality from Bacille Calmette-Guérin (BCG) infections after BCG instillation therapy.

OBJECTIVES: To investigate the incidence of and mortality associated with Bacille Calmette-Guérin (BCG) infections in a Finnish population of patients with bladder cancer treated with BCG instillations. MATERIALS AND METHODS: We conducted a nationwide register study and identified patients with BCG infections in Finland during 1996 to 2016 using the Finnish Cancer Registry and the Finnish National Infectious Diseases Register. We estimated the number of patients treated with BCG instillations based on data on national consumed BCG doses used to treat patients with bladder cancer, and calculated the annual incidence proportion of BCG infections. We further performed a detailed medical chart review to describe the clinical features and outcomes of the treated BCG infections. RESULTS: In total, 87 patients with BCG infection after BCG treatment of bladder cancer were identified. The incidence proportion increased gradually, yielding a cumulative incidence proportion of 2.5% during the latter half of the study period. BCG infections led to significant mortality, with 10% overall mortality and 17.5% mortality from systemic infections, which is notably higher than previously reported. CONCLUSION: The incidence proportion of BCG infections among bladder cancer patients treated with BCG has increased in Finland up to 2.5% at a nationwide level, with a notably higher mortality rate than previously reported.

Pathological and oncological outcomes in patients with sarcomatoid differentiation undergoing cystectomy.

OBJECTIVE: To evaluate whether urothelial carcinoma (UC) with sarcomatoid differentiation is associated with a lower pathological response rate to neoadjuvant chemotherapy (NAC) and worse oncological outcomes compared to UC without variant histology among patients undergoing radical cystectomy. PATIENTS AND METHODS: Patients with UC undergoing cystectomy from 1995 to 2018 at the Memorial Sloan Kettering Cancer Centre were identified. Patients with sarcomatoid differentiation at transurethral resection (TUR) or cystectomy, and patients without variant histology were selected. Downstaging from ≥cT2 to ≤pT1N0 defined partial response and pT0N0 defined complete response. Recurrence-free, cancer-specific and overall survival were modelled. RESULTS: We identified 131 patients with sarcomatoid differentiation and 1722 patients without variant histology, of whom 25 with sarcomatoid histology on biopsy and 313 without variant histology received NAC. Those with sarcomatoid differentiation presented with higher consensus tumour stage (94% ≥T2 vs 62%; P < 0.001) and were, therefore, more likely to receive NAC (29% vs 18%; P = 0.003). We found no evidence to support a difference in partial (24% vs 31%) or complete (20% vs 24%) response between patients with sarcomatoid histology and those with pure UC at TUR (P = 0.6). Among patients with sarcomatoid differentiation, 5-year recurrence-free survival was 55% (95% confidence interval [CI] 41-74) among patients receiving NAC and 40% (95% CI 31-52) among patients undergoing cystectomy alone (P = 0.1). Adjusting for stage, nodal involvement, margin status and receipt of NAC, sarcomatoid differentiation was associated with worse recurrence-free (hazard ratio [HR] 1.82, 95% CI 1.39-2.39), disease-specific (HR 1.66, 95% CI 1.23-2.22), and overall survival (HR 1.37, 95% CI 1.06-1.78). CONCLUSIONS: Sarcomatoid differentiation was associated with higher stage at presentation and independently associated with worse survival. Given similar pathological response rates if sarcomatoid differentiation is detected at initial resection, and greater survival among patients receiving NAC, treatment with NAC appears warranted. Other drivers of the poor outcomes of this histology must be investigated.