BACKGROUND AND OBJECTIVE:To determine whether the existing European Organisation for Research and Treatment of Cancer (EORTC) QLQ-NMIBC24 and QLQ-BLM30 modules remain fit for purpose and to assess health-related quality of life (HRQoL) issues relevant for patients with metastatic bladder cancer (mBC). METHODS:Following the EORTC Quality of Life Group (QLG) guidelines, phase 1 included an expert meeting, five systematic reviews, and interviews with 14 healthcare professionals (HCPs) and 48 bladder cancer (BC) patients across six countries. HRQoL issues were identified through the literature and rated by HCPs and patients for relevance and importance. Decision rules guided selection for phase 2. In phase 2, selected issues were translated into items using the EORTC Item Library and expert consensus. KEY FINDINGS AND LIMITATIONS:A total of 443 articles and 62 interviews yielded 150 unique HRQoL issues; 40 issues and two branching questions were retained for the provisional module. Seventeen new items were added beyond the existing EORTC BC modules, while 11 existing items were excluded. Issues specific to mBC and newer treatments, such as immunotherapy, were identified. Limitations include potential selection bias due to purposive sampling and small sample sizes per treatment subgroup. CONCLUSIONS AND CLINICAL IMPLICATIONS:This phase 1-2 study supports the need to update the existing EORTC BC modules and incorporate additional items relevant to all disease stages, including mBC. A single, flexible module with branching logic may improve clinical applicability across patient subgroups. The provisional module will undergo international pretesting and psychometric evaluation in phase 3.

To evaluate the oncological outcomes of second-look transurethral resection of bladder tumor (TURBT) in patients with a high grade (HG) Ta non-muscle invasive bladder cancer (NMIBC). We conducted a real-life multicenter study including all consecutive patients with HG Ta NMIBC, with or without second TURBT. Oncological outcomes included disease recurrence and progression. Multivariable Cox regression analyses were used to identify the independent predictors of bladder recurrence and progression. Of the 447 patients with HG Ta NMIBC, 240 (53.7

Objectives: To investigate the rate and predictors of recurrence at second-look ureterorenoscopy (URS) and to assess the adequate timeframe for second-look URS in upper tract urothelial carcinoma (UTUC). Methods: This multicenter retrospective study included 179 patients who underwent endoscopic kidney-sparing surgery (KSS) and second-look URS for non-invasive UTUC between 2004 and 2017. We performed logistic and Cox proportional hazard regression analyses to investigate the association between clinical parameters and second-look recurrence, recurrence-free survival (RFS), and cancer-specific mortality. The optimal duration to second-look URS was extrapolated using restricted cubic splines. Results: Overall, 66 (36.9%) patients experienced recurrence at second-look URS. After second-look URS, further recurrence was observed in 87 (48.6%) patients during a median follow-up of 12 months. Female gender (OR [odds ratio] 2.3, 95% CI [confidence interval] 1.1–4.7, p = 0.026) and tumor size > 1 cm (OR 3.3, 95% CI 1.2–9.5, p = 0.027) were independently associated with recurrence at second look. Second-look recurrence was a strong prognostic factor for RFS (HR 5.0, 95% CI 3.1–8.0, p < 0.001). Second-look URS between 5 and 12 weeks after initial endoscopic laser ablation was an independent favorable factor for RFS (HR 0.5, 95% CI 0.3–0.9, p = 0.014). Conclusions: Early recurrence at second-look URS appears to be one of the strongest predictive factors for RFS in patients undergoing endoscopic KSS. Our results suggest that second-look URS performed within 5 to 12 weeks is associated with a lower probability of further disease recurrence. Given that this interval was derived and tested in the same cohort, this finding should be regarded as hypothesis-generating and requires external validation before being adopted as a clinical standard.

PURPOSE:To assess the value of routine annual imaging in identifying complications more than 5 years after radical cystectomy (RC) with ileal conduit. METHODS:We included patients with bladder cancer who underwent RC with ileal conduit between 2011 and 2018. Patients were excluded if they received no functional follow up after discontinuing oncological follow up, if there was oncological progression or if an uretero-enteric structure (UES) was diagnosed within 5 years after RC. Functional follow up consisted of annual imaging using either ultrasound or CT, along with laboratory tests. The primary outcomes were: (1) the incidence of new or progressive hydronephrosis, and (2) the incidence of imaging-diagnosed complications i.e. UES and urolithiasis. RESULTS:A total of eighty-two patients were included, with a mean follow up of 6.5 years after RC. In total, 202 ultrasounds and 71 CTs were performed. New or progressive hydronephrosis was observed in 6 imaging modalities (2.2%), in 6 different patients (7.3%). No UES cases were diagnosed following routine annual imaging. One patient was diagnosed with UES after diagnostic imaging was prompted by clinical symptoms. CONCLUSION:In our cohort, routine annual imaging beyond five years after radical cystectomy (RC) with ileal conduit rarely revealed abnormalities and did not contribute to the diagnosis of UES nor urolithiasis. However, imaging should be performed when clinically indicated.

Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease, with Ta tumors accounting for about 70

[¹⁸F]FDG‑PET/CT is increasingly used to stage invasive bladder cancer (IBC), resulting in growing demand at tertiary centres for time‑intensive second‑opinion reading of externally acquired scans. However, the incremental clinical value of routine reinterpretation is unclear. We evaluated the clinical impact of second‑opinion [¹⁸F]FDG‑PET/CT reading in a centralised referral network in the Netherlands. In this multicentre retrospective diagnostic cohort study, consecutive patients with histologically confirmed high-grade IBC who underwent externally acquired [¹⁸F]FDG‑PET/CT followed by expert second‑opinion reading at two tertiary centres were evaluated. Initial staging reports were compared with second-opinion staging assessments. Clinically meaningful discrepancies were defined as changes in nodal status (cN0 vs. cN+) or distant metastatic status (cM0 vs. cM1 or cM1a vs. cM1b). Treatment recommendation changes directly attributable to second-opinion reading were recorded. Six hundred patients were included. Agreement between initial and second‑opinion reading was high for both nodal and metastatic staging (κ = 0.89 and κ = 0.87, respectively). Clinically meaningful discrepancies occurred in 33 patients (5.5

To evaluate the impact of detrusor muscle (DM) absence on oncological outcomes in patients with pTaHG within a large, multicenter cohort. This is a retrospective multicenter study based on a national database including 12 international expert centers. All patients who underwent transurethral resection of bladder tumor (TURBT) for a new diagnosis of pTaHG bladder cancer between January 2010 and December 2018 were included and divided into two groups according to the presence or absence of DM. Kaplan-Meier curves were used to illustrate survival outcomes, while Cox regression analyses were conducted to identify independent predictors of survival. Overall, 418 patients had either pTaHG with DM (n = 365;87.3

Background and objective:Preoperative anemia is common in patients undergoing radical cystectomy for bladder cancer, but its prevalence and impact on outcomes remain poorly characterized across different health care settings. This study aims to assess the prevalence of preoperative anemia, evaluate its current management practices, and determine its association with postoperative and oncological outcomes in patients undergoing radical cystectomy. Methods:We retrospectively analyzed 4886 patients with nonmetastatic bladder cancer who underwent radical cystectomy across 28 centers in 13 countries. Multivariable regression models identified the predictors of preoperative hemoglobin levels and postoperative blood transfusions. Survival outcomes were assessed using Kaplan-Meier and Cox proportional hazards regression analyses. Key findings and limitations:Preoperative anemia was present in 44% of women and 48% of men. Among anemic patients, 73% received no blood management interventions. Higher hemoglobin levels before transurethral resection of a bladder tumor correlated with higher levels before cystectomy and fewer postoperative blood transfusions (odds ratio: 0.98, 95% confidence interval [CI]: 0.97-0.99, p < 0.001). Higher preoperative hemoglobin levels were associated with lower 90-d mortality rates (hazard ratio: 0.98, 95% CI: 0.97-0.99, p < 0.001) and independently predicted reduced all-cause mortality, cancer-specific mortality, and disease relapse. Conclusions and clinical implications:Preoperative anemia is prevalent and undertreated in patients undergoing radical cystectomy, and is independently associated with adverse perioperative and oncological outcomes. This highlights the need for further research regarding the potential benefits of implementing systematic preoperative anemia management. Patient summary:This study found that low blood counts before bladder removal surgery are common, often untreated, and linked to worse outcomes. Early treatment of low blood counts before surgery could improve results for patients.

INTRODUCTION/BACKGROUND:A recent study reported that patients with residual urothelial carcinoma of the bladder subsequent to neoadjuvant/induction chemotherapy (NAIC) prior to RC exhibited inferior oncological outcomes in comparison to pathological stage-matched patients who underwent upfront RC. Our hypothesis is that this may be ascribed to variations in preoperative CT-stage rather than the impact of chemotherapy. PATIENTS AND METHODS:This retrospective multicentre study included 513 patients who underwent RC for cT2-4N0-3M0 disease between 2010 and 2017. Patients were categorized based on pathological outcomes: pathological complete response (pCR, (y)pT0N0), complete downstaging (pCD, (y)pT0/is/a/1N0) and residual muscle-invasive and/or node positive disease (rMIBC, (y)pT2-4N0 and/or (y)pN1-3). RESULTS:Of the total cohort, 175 (34.1%) patients underwent NAIC+RC, while 338 (65.9%) underwent upfront RC. NAIC+RC patients exhibited lower age and CCI-scores, along with higher cT&N-stage (all P-values < .001). The mOS was 60.5 months for NAIC+RC and 49.4 months for upfront RC (P-value = .171). In patients with rMIBC, survival was inferior after NAIC+RC compared to upfront RC. However, the clinical stage distribution between NAIC+RC and upfront RC was imbalanced, with 3% versus 49% cT2N0 patients and 47% versus 9% cT4b and/or N+ patients, respectively. Following adjustments for cT & N-stage, age, and CCI-scores in multivariable Cox proportional-hazards analysis, worse OS was associated with upfront RC (HR 1.52, [95% CI, 1.11-2.10], P-value = .009). CONCLUSION:The observed inferior survival in cT2-4N0-3M0 patients with rMIBC after NAIC+RC compared to those undergoing upfront RC resulted from worse preoperative characteristics, including clinical stage. The representation of clinical disease stage should not be overlooked in survival analyses.

OBJECTIVES:To evaluate the current European Association of Urology/American Society of Clinical Oncology follow-up (FU) schedule with routine use of ultrasonography (US) ± US-guided fine-needle aspiration cytology (FNAC) in patients with lymph node (LN)-negative penile squamous cell carcinoma (PSCC). PATIENTS AND METHODS:We evaluated FU outcomes for low-risk clinically LN-negative (cN0) and intermediate- to high-risk sentinel node (SN) negative (pathological N-stage [pN]0) patients with PSCC at a high-volume centre. We analysed routine inguinal US ± FNAC (in case of a suspicious LN) during FU. A competing risk analysis was performed to calculate the cumulative risk of LN metastases in these groups, with local recurrence as competing risk. RESULTS:A total of 201 patients with PSCC were analysed, with 2694 inguinal US investigations being evaluated. FNAC was performed during 270 US procedures (10.0%). A LN metastasis was found in four of 270 US + FNAC procedures (1.5%, 0.2% of all US). All tumours were intermediate- to high-risk tumours. Three occurred within the first year after primary treatment, and one at 20 months. The cumulative risk of developing LN metastases in cN0 low-risk tumours was 0% (no events occurred) and in SN-negative intermediate- to high-risk group 2.0%, both at 1 year of FU. Two (out of four) patients with LN recurrence died from disease. CONCLUSION:After adequate staging and treatment, patients with cN0/pN0 PSCC rarely develop LN metastasis during FU. As these metastases generally occur within 1 year after treatment, we recommend (3-monthly) routine inguinal US only during the first year of FU. Thereafter, the frequency of FU visits and examinations can be reduced in patients capable of self-examination of the penis, resulting in a substantial (up to a 50%) reduction of FU visits compared to current guideline recommendations.

BACKGROUND:Pre-operative immune checkpoint blockade (ICB) with ipilimumab and nivolumab has shown encouraging pathological complete response (pCR) rates in stage III urothelial cancer (UC). A previous analysis of NABUCCO suggested that ipilimumab 3 mg/kg is more effective than ipilimumab 1 mg/kg. However, long-term progression-free and overall survival (PFS, OS) following pre-operative combination ICB are unknown. METHODS:In NABUCCO, 54 patients received pre-operative ipilimumab plus nivolumab in different dosing regimens. PFS and OS were determined for the entire NABUCCO population and various clinically relevant subgroups. We explored ICB effects on the cellular composition of tumor-draining lymph nodes (tdLN) from ICB-treated patients (n = 5) and untreated or chemotherapy-treated patients (n = 5) using multiplex immunofluorescence for the PhenoCycler Fusion (Akoya). RESULTS:With a median follow-up of 70 months, PFS and OS at 60 months were 67 % and 70 %, respectively, for the entire study. PFS and OS at 60 months were similar for patients with residual non-muscle invasive UC (NMIBC) and patients with a pCR. The presence of a nodal micrometastasis (<2 mm) after ICB, the development of grade ≥ 3 immune-related adverse events (irAE) and corticosteroids or antibiotics did not negatively impact survival. We observed smaller distances from CD20+ cells to CD14+ cells in tdLN following ICB compared to tdLN from untreated or chemotherapy-treated patients. CONCLUSIONS:Our data demonstrate a 5-year PFS of 67 % and OS of 70 % after pre-operative ICB in stage III UC. Survival was not impaired for patients with residual NMIBC, a nodal micrometastasis at resection, grade ≥ 3 irAE or corticosteroid use. CLINICAL TRIAL REGISTRATION NUMBER:NCT03387761.

Introduction and objective: Imiquimod (IQ) is an immunomodulator used in the management of penile intraepithelial neoplasia (PeIN) lesions. However, IQ treatment maybe associated with bothersome side effects (SEs). To date, studies reporting on this morbidity and evaluating predictors of response to IQ are scarce and included small cohorts. The primary objective of our study was to assess the response to IQ treatment, associated SEs, and potential predictors of response in the largest reported cohort to date. Methods: We conducted a collaborative retrospective study involving patients diagnosed with PeIN and treated with IQ between 2010 and 2022 in two high-volume centers in the Netherlands and Belgium. Eligible patients had a confirmed diagnosis of PeIN and a minimum of 6-mo follow-up. Response to IQ was categorized as a complete response (CR), partial response, or no response. Descriptive statistics were generated and statistical tests included the Mann-Whitney U test for age and Fisher's exact test for categorical variables. Key findings and limitations: The study included a total of 44 patients, with a median age of 65.4 yr (interquartile range 56-72). Of these patients, 28 (64%) achieved a CR, while 14 (32%) had a partial response and two (4.5%) had no response. In the CR subgroup, the 3-yr recurrence rate was 25%. No significant correlation was found between response status and age, human papillomavirus status, history of penile cancer, or circumcision before treatment. Among the patients, 50% reported SEs, mainly local pain, irritation, and bleeding, and 12% discontinued treatment because of SEs. There was no significant correlation between CR and the incidence or type of SE. Conclusions and clinical implications: Despite the high overall response rate to IQ, a significant number of patients experienced local recurrence within 3 yr, and approximately half of the patients reported SEs. Our results did not identify any clinical or pathological factors or local SEs predictive of the therapeutic response to IQ. Prospective studies are needed to help in predicting which patients are likely to respond to IQ so that those who will not benefit can be spared the SEs associated with this treatment. Patient summary: Our study looked at responses to imiquimod (IQ), an immune- based treatment in cream format, for precancerous lesions on the penis, called penile intraepithelial neoplasia. More than 95% of patients had a complete or partial response to IQ, but 50% reported side effects, and 25% of the group with a complete response had recurrence within 3 years. More research is needed to help in selecting patients who will benefit the most from IQ treatment. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of European Associa tion of Urology. This is an open access article under the CC BY license (http://creativecom org/licenses/b mons. y/4.0/).

Background and objective: Intravesical instillation of chemotherapy (IIC) after radical surgery for upper urinary tract urothelial carcinoma (UTUC) reduces the risk of intravesical recurrence (IVR). However, compliance is low because of possible extravesical leakage after bladder cuff excision. The aim of this study was to evaluate the efficacy of preoperative IIC in reducing the risk of IVR. Methods: In this prospective, single-arm, multi-institutional, phase 2 clinical trial, 190 chemona & iuml;ve patients with primary UTUC without prior or concurrent bladder cancer received a single intravesical instillation of mitomycin C for 1-2 hr within 3 h before surgery. The primary endpoint was the 2-yr histologically confirmed IVR rate, with a target reduction of >40% (from 33.2% according to literature data to <20%). A historical cohort of 247 patients with UTUC who did not receive perioperative IIC served as the reference. Secondary endpoints included compliance, toxicity, and IVR-free survival, which was analyzed via multivariable Cox regression and stratified by previous diagnostic ureteroscopy (d-URS). Key findings and limitations: The 2-yr IVR rate was 24% (95% confidence interval [CI] 18-31%) on intention-to-treat analysis and 23% (95% CI 13-32%) on per-protocol analysis. Multivariable analysis revealed that d-URS was associated with higher IVR risk. In the REBACARE cohort, patients without d-URS had threefold lower IVR risk (hazard ratio 0.33, 95% CI 0.12-0.87) in comparison to the reference cohort. Compliance with preoperative instillation was 96% and no grade >2 toxicity occurred. Conclusions and clinical implications: Preoperative IIC with mitomycin C was feasible and well tolerated and significantly reduced IVR risk for patients without d-URS. These findings suggest that preoperative IIC is a viable strategy for this subset of UTUC patients and that d-URS should be performed judiciously. (c) 2024 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).

ObjectiveTo evaluate penile squamous cell carcinoma (PSCC) incidence and centralisation trends in the Netherlands over the past three decades, as well as the effect of centralisation of PSCC care on survival.Patients and methodsIn the Netherlands PSCC care is largely centralised in one national centre of expertise (Netherlands Cancer Institute [NCI], Amsterdam). For this study, the Netherlands Cancer Registry, an independent nationwide cancer registry, provided per‐patient data on age, clinical and pathological tumour staging, follow‐up, and vital status. Patients with treatment at the NCI were identified and compared to patients who were treated at all other centres. The age‐standardised incidence rate was calculated with the European Standard Population. The probability of death due to PSCC was estimated using the relative survival. Multivariable Cox regression analysis was performed to evaluate predictors of survival.ResultsA total of 3160 patients were diagnosed with PSCC between 1990 and 2020, showing a rising incidence (P < 0.001). Annual caseload increased at the NCI (1% in 1990, 65% in 2020) and decreased at other (regional) centres (99% to 35%). Despite a relatively high percentage of patients with T2–4 (64%) and N+ (33%) at the NCI, the 5‐year relative survival was higher (86%, 95% confidence interval [CI] 82–91%) compared to regional centres (76%, 95% CI 73–80%, P < 0.001). Patients with a pathological T2 tumour were treated with glans‐sparing treatment more often at the reference centre than at the regional centres (16% vs 5.0%, P < 0.001). After adjusting for age, histological grading, T‐stage, presence of lymph node involvement and year of diagnosis, treatment at regional centres remained a predictor for worse survival (hazard ratio 1.22, 95% CI 1.05–1.39; P = 0.006).ConclusionThe incidence of PSCC in the Netherlands has been gradually increasing over the past three decades, with a noticeable trend towards centralisation of PSCC care and improved relative survival rate.

Background and objective: The possible negative impact of radical surgery on patients’ health-related quality of life (HRQoL) plays an important role in preoperative counseling. Here, we analyzed the HRQoL of patients treated for upper urinary tract urothelial carcinoma (UTUC) in the context of a single-arm phase 2 multicenter study, in which the safety and efficacy of a single preoperative intravesical instillation with mitomycin C were investigated. Our objective was to investigate early changes in HRQoL in patients undergoing radical surgery for UTUC and identify factors associated with these outcomes. Methods: Patients with pTanyN0-1M0 UTUC were prospectively included. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) questionnaire at baseline, and at 1 and 3 mo after surgery. A linear mixed model was used to evaluate the changes in HRQoL over time and identify the variables associated with these outcomes. The clinical effect size was used to assess the clinical impact and level of perceptibility of HRQoL changes for clinicians and/or patients based on given thresholds. Key findings and limitations: Between 2017 and 2020, 186 patients were included. At baseline, 1 mo after surgery, and 3 mo after surgery, response rates were 91%, 84%, and 78%, respectively. One month after surgery, a statistically significant and clinically relevant deterioration was observed in physical, role, and social functioning, and for the included symptom scales: constipation, fatigue, and pain. An improvement in emotional functioning was observed. At 3 mo, HRQoL returned to baseline levels, except emotional functioning, which improved at 1 mo and persisted to be better than that before surgery. Age >70 yr was associated with worse physical functioning, but better social and emotional functioning. Male patients reported better emotional functioning than females. Postoperative complications were negatively associated with social functioning. Conclusions and clinical implications: UTUC patients treated with radical surgery experienced a significant, albeit temporary, decline in HRQoL. Three months following surgery, HRQoL outcomes returned to baseline levels. This information can be used to counsel UTUC patients before undergoing radical surgery and contextualize recovery after surgery. Patient summary: We investigated the changes in quality of life as reported by patients who underwent surgery for upper tract urothelial carcinoma (UTUC). We found that patients experienced a decline in quality of life 1 mo after surgery, but this was temporary, with full recovery of quality of life 3 mo after surgery. These findings can help doctors and other medical staff in counseling UTUC patients before undergoing radical surgery.

OBJECTIVES:To investigate changes in quality of life (QoL) up to 8 years after radical cystectomy (RC) and compare QoL after RC with a gender- and age-matched Dutch normative population. Furthermore, we aimed to identify patient characteristics associated with QoL and QoL trajectories after RC. PATIENTS AND METHODS:Patients with bladder cancer were invited to complete QoL questionnaires at 3-month intervals in the first year and yearly thereafter. Follow-up data were available for a maximum of 8 years. We used linear mixed-effect models to investigate changes in QoL subscales (physical functioning [PF], emotional functioning [EF], and QoL summary score [QoL-sum]) over time, and to identify potential demographic and clinical correlates of QoL and QoL trajectories (i.e., interaction with time). RESULTS:Data from 278 patients was included. Post-RC EF scores increased from 83.7 (95% confidence interval [CI] 81.7-85.6) to levels comparable to the normative population (90.1) 8 years after RC. PF (post-RC: 82.4, 95% CI 78.5-86.3) and QoL-sum (post-RC: 88.2, 95% CI 85.2-91.2) remained lower compared to the normative population (88.9 and 91.4, respectively) 8 years after RC. Compared to patients with an American Society of Anesthesiologists (ASA) score of 1 at diagnosis, those with ASA score 2 or ASA score 3 had significant lower post-RC PF (mean difference (MD) = -8 and -22, respectively; P < 0.001), EF (MD = -1 and -11; P = 0.5 and P < 0.01) and QoL-sum (MD = -2 and -9; P = 0.2 and P < 0.01). In addition, patients with a higher ASA score had a worse QoL-sum trajectory (Pinteraction = 0.01). Older patients had a worse PF trajectory (Pinteraction < 0.01) but higher post-RC EF (P < 0.01). CONCLUSIONS:Directly after RC, patients have lower PF, EF and QoL-sum, compared to a normative population. Notably, EF recovers to normative levels over a period of 8 years after RC. Clinicians are encouraged to administer supportive care interventions to enhance the QoL for patients undergoing RC, especially targeting older patients and those with higher ASA scores.

Cohort 1 of the phase 1B NABUCCO trial showed high pathological complete response (pCR) rates with preoperative ipilimumab plus nivolumab in stage III urothelial cancer (UC). In cohort 2, the aim was dose adjustment to optimize responses. Additionally, we report secondary endpoints, including efficacy and tolerability, in cohort 2 and the association of presurgical absence of circulating tumor DNA (ctDNA) in urine and plasma with clinical outcome in both cohorts. Thirty patients received two cycles of either ipilimumab 3 mg kg −1 plus nivolumab 1 mg kg −1 (cohort 2A) or ipilimumab 1 mg kg −1 plus nivolumab 3 mg kg −1 (cohort 2B), both followed by nivolumab 3 mg kg −1 . We observed a pCR in six (43%) patients in cohort 2A and a pCR in one (7%) patient in cohort 2B. Absence of urinary ctDNA correlated with pCR in the bladder (ypT0Nx) but not with progression-free survival (PFS). Absence of plasma ctDNA correlated with pCR (odds ratio: 45.0; 95% confidence interval (CI): 4.9–416.5) and PFS (hazard ratio: 10.4; 95% CI: 2.9–37.5). Our data suggest that high-dose ipilimumab plus nivolumab is required in stage III UC and that absence of ctDNA in plasma can predict PFS. ClinicalTrials.gov registration: NCT03387761 .

Background: Head-to-head comparisons between ileal conduit (IC) and orthotopic neobladder (ONB) in terms of peri-and postoperative outcomes and complications, in the specific setting of robot-assisted radical cystectomy (RARC), are not available.Objective: To address the impact of the type of urinary diversion (UD, IC vs ONB) on RARC morbidity, as well as operative time (OT), length of stay (LOS), and readmissions.Design, setting, and participants: Urothelial bladder cancer patients treated with RARC at nine high-volume European institutions between 2008 and 2020 were identified. Intervention: RARC with either IC or ONB.Outcome measurements and statistical analysis: Intra-and postoperative complica-tions were collected and reported according to the Intraoperative Complications Assessment and Reporting with Universal Standards recommendations and European Association of Urology guidelines, respectively. Multivariable logistic regression models tested the impact of UD on outcomes, after adjustment for clus-tering at single hospital level.Results and limitations: Overall, 555 nonmetastatic RARC patients were identified. In 280 (51%) and 275 (49%) patients, an IC and an ONB were performed, respectively. Eighteen intraoperative complications were recorded. The rates of intraoperative complications were 4% in IC patients and 3% in ONB patients (p = 0.4). The median LOS and readmission rates were 10 versus 12 d (p < 0.001) and 20% versus 21% (p = 0.8) in IC versus ONB patients, respectively. At a multivariable logistic regres-sion analyses, the type of UD (IC vs ONB) reached the independent predictor status for prolonged OT (odds ratio [OR]: 0.61, p = 0.03) and prolonged LOS (OR: 0.34, p < 0.001), but not for readmission (OR: 0.92, p = 0.7). Overall, 513 postoperative complications were experienced by 324 patients (58%). At least one postoperative complication was experienced by 160 (57%) IC patients versus 164 (60%) ONB patients (p = 0.6). The type of UD reached the status of an independent predictor of UD-related complications (OR: 0.64, p = 0.03). Conclusions: Compared with RARC with ONB, RARC with IC is less prone to UD-related postoperative complications, prolonged OT, and prolonged LOS.Patient summary: To date, the impact of the type of urinary diversion, namely, ileal conduit versus orthotopic neobladder, on peri-and postoperative outcomes of robot-assisted radical cystectomy is unknown. Based on a rigorous data accrual, which relied on established complication reporting systems (Intraoperative Complications Assessment and Reporting with Universal Standards and European Association of Urology recommended systems), we reported intra-and postopera-tive complications according to urinary diversion type. Moreover, we found that ileal conduit was associated with lower operative time and length of stay, and yielded a protective effect in terms of urinary diversion-related complications.(c) 2023 The Authors. Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY-NC-ND license (http://creative-commons.org/licenses/by-nc-nd/4.0/).