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Background: Robotic-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) is surging worldwide. Aim of the study was to perform a multicentric cost-analysis of RARC by comparing the gross cost of the intervention across hospitals in four different European countries., Methods: Patients who underwent RARC + ICUD were recruited from eleven European centers in four European countries (Belgium, France, Netherlands, and UK) between 2015 and 2020. Costs were divided into six parts: cost for hospital stay, cost for ICU stay, cost for surgical theater occupation, cost for transfusion, cost for robotic instruments, and cost for stapling instruments. These costs were individually assessed for each patient., Results: A total of 490 patients were included. Median operative time was 300(270-360) minutes and median hospital length-of-stay was 11(8-15) days. The average total cost of RARC was 14.794€ (95%CI 14.300-15.200€). A significant difference was found for the total cost, as well as the various subcosts abovementioned, between the four included countries. Different sets and types of robotic instruments were used by each center, leading to a difference in cost of robotic instrumentation. Nearly 84% of costs of RARC were due to hospital stay (42%), ICU stay (3%) and operative time (39%), while 16% of costs were due to robotic (8%) and stapling (8%) instruments., Conclusion: Costs and subcosts of RARC + ICUD vary significantly across European countries and are mainly dependent of hospital length-of-stay and operative time rather than robotic instrumentation. Decreasing length-of-stay and reducing operative time could help to decrease the cost of RARC and make it more widely accessible., Competing Interests: Declaration of competing interest Guillaume Ploussard: COI with Intuitive®. The rest of co-authors have no conflict-of-interest to disclose., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Introduction: Urachal adenocarcinoma (UrAC) is a very rare malignancy with a poor prognosis. The role of preoperative serum tumor markers (STMs) in UrAC is unknown. The aim of this study was to assess the clinical value of elevated STMs including carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9), cancer antigen 125 (CA125), and cancer antigen 15-3 (CA15-3) in surgically treated UrAC, and to evaluate their prognostic significance., Methods: This was a retrospective study of consecutive patients with histopathologically confirmed UrAC who underwent surgical treatment at a single tertiary hospital. Blood levels of CEA, CA19-9, CA125, and CA15-3 were determined before surgery. The proportion of patients with elevated STMs was calculated, as well as the association between elevated STMs and clinicopathological characteristics, recurrence-free survival and disease-specific survival., Results: Of the 50 patients included; CEA, CA 19-9, CA125, and CA15-3 were elevated in 40%, 25%, 26%, and 6% respectively. Elevated CEA was associated with higher pT-stage (odds ratio [OR] 3.3 [95% confidence interval 1.0-11.1], P = 0.003), higher Sheldon stage (OR 6.9 [95% CI 0.8-60.4], P = 0.01), male sex (OR 4.7 [95% CI 1.2-18.3], P = 0.01), and the presence of peritoneal metastases at the time of diagnosis (OR 3.5 [95% CI 0.9-14.2], P = 0.04). Elevated CA19-9 was associated with signet-cell component (OR 1.7 [95% CI 0.9-3.3], P = 0.03) and elevated CA125 was associated with peritoneal metastases at the time of diagnosis (OR 6.0 [95% CI 1.2-30.6], P = 0.04). Elevated STMs before surgery were not associated with recurrence-free survival and/or disease-specific survival., Conclusion: A subset of patients with surgically treated UrAC has elevated STMs preoperatively. CEA was most frequently (40%) elevated and correlated with unfavorable tumor characteristics. However, STM levels did not correlate with prognostic outcomes., Competing Interests: Conflict of interest The authors have nothing to report., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction and Objectives: 18F-fluorodeoxyglucose positron-emission tomography-computed tomography (FDG-PET/CT) is increasingly used in the preoperative staging of patients with muscle-invasive bladder cancer. The clinical added value of FDG-PET/CT in high-risk non-muscle invasive bladder cancer (NMIBC) is unknown. In this study, the value of FDG-PET/CT in addition to contrast enhanced (CE)-CT was evaluated in high-risk NMIBC before radical cystectomy (RC)., Materials and Methods: This is a retrospective analysis of consecutive patients with high risk and very-high risk urothelial NMIBC scheduled for RC in a tertiary referral center between 2011 and 2020. Patients underwent staging with CE-CT (chest and abdomen/pelvis) and FDG-PET/CT. We assessed the clinical disease stage before and after FDG-PET/CT and the treatment recommendation based on the stage before and after FDG-PET/CT. The accuracy of CT and FDG-PET/CT for identifying metastatic disease was defined by the receiver-operating curve using a reference-standard including histopathology/cytology (if available), imaging and follow-up., Results: A total of 92 patients were identified (median age: 71 years). In 14/92 (15%) patients, FDG-PET/CT detected metastasis (12 suspicious lymph nodes and 4 distant metastases). The disease stage changed in 11/92 (12%) patients based on additional FDG-PET/CT findings. FDG-PET/CT led to a different treatment in 9/92 (10%) patients. According to the reference standard, 25/92 (27%) patients had metastases. The sensitivity, specificity and accuracy of FDG-PET/CT was 36%, 93% and 77% respectively, versus 12%, 97% and 74% of CE-CT only. The area under the ROC curve was 0.643 for FDG-PET/CT and 0.545 for CT, P = .036., Conclusion: The addition of FDG-PET/CT to CE-CT imaging changed the treatment in 10% of patients and proved to be a valuable diagnostic tool in a selected subgroup of NMIBC patients scheduled for RC., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: To determine the association between the FGFR3 mutation status and immuno-histochemistry (IHC) markers (p53 and Ki-67) in invasive bladder cancer (BC), and to analyze their prognostic value in a multicenter, multi-laboratory radical cystectomy (RC) cohort., Patients and Methods: We included 1058 cN0M0, chemotherapy-naive BC patients who underwent RC with pelvic lymph-node dissection at 8 hospitals. The specimens were reviewed by uro-pathologists. Mutations in the FGFR3 gene were examined using PCR-SNaPshot; p53 and Ki-67 expression were determined by standard IHC. FGFR3 mutation status as well as p53 (cut-off>10%) and Ki-67 (cut-off>20%) expression were correlated to clinicopathological parameters and disease specific survival (DSS)., Results: pT-stage was

Background: Urachal carcinoma (UrC) is a rare malignancy that often presents at an advanced stage with metastases in up to a quarter of patients. There is no consensus on the optimal form of staging for patients with UrC. In the present study, we evaluated the diagnostic value of 18 F-fluorodeoxyglucose-positron emitted tomography/computed tomography (FDG-PET/CT) for UrC., Patients and Methods: We evaluated 40 consecutive patients who were staged for urachal cancer between 2010 and 2020. They underwent a total of 62 FDG-PET/CTs (40 for primary staging, and 22 during follow-up), which were compared with standard-of-care contrast-enhanced CT (CECT). The metabolic detection of primary tumors, lymph node metastases (LNMs), peritoneal metastases (PMs), distant metastases (DMs), and local recurrence by FDG-PET/CT was evaluated. Sensitivity and specificity were calculated compared with CECT. Histopathology or follow-up imaging was the reference standard., Results: Of all 40 patients, 33 patients (83%) had urachal adenocarcinoma-26 (65%) with a mucinous component and 7 (17%) with invasive urothelial carcinoma. All local UrC tumors could be visualized on CT, and 80% showed increased FDG uptake. At initial staging, FDG-PET/CT detected FDG-avid LNMs, PMs, and DMs in 50%, 17%, and 25% of patients, respectively. These metastases were also visualized on CECT. During follow up, FDG-PET/CT revealed FDG-avid local recurrences that were not seen on CT in two out of eight patients (25%)., Conclusion: The present study demonstrates that most UrC can be visualized on FDG-PET/CT. At initial diagnosis, FDG-PET/CT does not seem to yield additional information compared with CECT; however, FDG-PET/CT may be helpful during follow-up. This is a small study, and the findings should be corroborated with larger series., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To assess the effect of patient's sex on response to neoadjuvant chemotherapy (NAC) in patients with clinically nonmetastatic muscle-invasive bladder cancer (MIBC)., Methods: Complete pathologic response, defined as ypT0N0 at radical cystectomy, and downstaging were evaluated using sex-adjusted univariable and multivariable logistic regression modeling. We used interaction terms to account for age of menopause and smoking status. The association of sex with overall survival and cancer-specific survival was evaluated using Cox regression analyses., Results: A total of 1,031 patients were included in the analysis, 227 (22%) of whom were female. Female patients had a higher rate of extravesical disease extension (P = 0.01). After the administration of NAC, ypT stage was equally distributed between sexes (P = 0.39). On multivariable logistic regression analyses, there was no difference between the sexes or age of menopause with regards to ypT0N0 rates or downstaging (all P > 0.5). On Cox regression analyses, sex was associated with neither overall survival (hazard ratio 1.04, 95% confidence interval 0.75-1.45, P = 0.81) nor cancer-specific survival (hazard ratio 1.06, 95% confidence interval 0.71-1.58, P = 0.77)., Conclusion: Our study generates the hypothesis that NAC equalizes the preoperative disparity in pathologic stage between males and females suggesting a possible differential response between sexes. This might be the explanation underlying the comparable survival outcomes between sexes despite females presenting with more advanced tumor stage., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Papillary urothelial neoplasm of low malignant potential (PUN-LMP) was introduced as a noninvasive, noncancerous lesion and a separate grade category in 1998. Subsequently, PUN-LMP was reconfirmed by World Health Organization (WHO) 2004 and WHO 2016 classifications for urothelial bladder tumors., Objectives: To analyze the proportion of PUN-LMP diagnosis over time and to determine its prognostic value compared to Ta-LG (low-grade) and Ta-HG (high-grade) carcinomas. To assess the intraobserver variability of an experienced uropathologist assigning (WHO) 2004/2016 grades at 2 time points., Materials and Methods: Individual patient data of 3,311 primary Ta bladder tumors from 17 hospitals in Europe and Canada were available. Transurethral resection of the tumor was performed between 1990 and 2018. Time to recurrence and progression were analyzed with cumulative incidence functions, log-rank tests and multivariable Cox-regression stratified by institution. Intraobserver variability was assessed by examining the same 314 transurethral resection of the tumorslides twice, in 2004 and again in 2018., Results: PUN-LMP represented 3.8% (127/3,311) of Ta tumors. The same pathologist found 71/314 (22.6%) PUN-LMPs in 2004 and only 20/314 (6.4%) in 2018. Overall, the proportion of PUN-LMP diagnosis substantially decreased over time from 31.3% (1990-2000) to 3.2% (2000-2010) and to 1.1% (2010-2018). We found no difference in time to recurrence between the three WHO 2004/2016 Ta-grade categories (log-rank, P = 0.381), nor for LG vs. PUN-LMP (log-rank, P = 0.238). Time to progression was different for all grade categories (log-rank, P < 0.001), but not between LG and PUN-LMP (log-rank, P = 0.096). Multivariable analyses on recurrence and progression showed similar results for all 3 grade categories and for LG vs. PUN-LMP., Conclusions: The proportion of PUN-LMP has decreased to very low levels in the last decade. Contrary to its reconfirmation in the WHO 2016 classification, our results do not support the continued use of PUN-LMP as a separate grade category in Ta tumors because of the similar prognosis for PUN-LMP and Ta-LG carcinomas., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: The neutrophil-to-lymphocyte ratio (NLR) is an attractive marker because it is derived from routine bloodwork. NLR has shown promise as a prognostic factor in muscle invasive bladder cancer (MIBC) but its value in patients receiving neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) is not yet established. Since NLR is related to an oncogenic environment and poor antitumor host response, we hypothesized that a high NLR would be associated with a poor response to NAC and would remain a poor prognostic indicator in patients receiving NAC., Methods: A retrospective analysis was performed on patients with nonmetastatic MIBC (cT2-4aN0M0) who received NAC prior to RC between 2000 and 2013 at 1 of 19 centers across Europe and North America. The pre-NAC NLR was used to split patients into a low (NLR ≤ 3) and high (NLR > 3) group. Demographic and clinical parameters were compared between the groups using Student's t test, chi-squared, or Fisher's exact test. Putative risk factors for disease-specific and overall survival were analyzed using Cox regression, while predictors of response to NAC (defined as absence of MIBC in RC specimen) were investigated using logistic regression., Results: Data were available for 340 patients (199 NLR ≤ 3, 141 NLR > 3). Other than age and rate of lymphovascular invasion, demographic and pretreatment characteristics did not differ significantly. More patients in the NLR > 3 group had residual MIBC after NAC than the NLR ≤ 3 group (70.8% vs. 58.3%, P = 0.049). NLR was the only significant predictor of response (odds ratio: 0.36, P = 0.003) in logistic regression. NLR was a significant risk factor for both disease-specific (hazard ratio (HR): 2.4, P = 0.006) and overall survival (HR:1.8, P = 0.02)., Conclusion: NLR > 3 was associated with a decreased response to NAC and shorter disease-specific and overall survival. This suggests that NLR is a simple tool that can aid in MIBC risk stratification in clinical practice., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Urachal adenocarcinoma (UrAC) is a rare malignancy arising from persistent urachal remnants, which can cause peritoneal metastases (PM). Currently, patients with this stage UrAC are considered beyond cure. Our objective is to report long-term oncological outcome after cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with PM of urachal adenocarcinoma (UrAC)., Materials and Methods: We identified 55 patients with UrAC treated at our hospital between 1994 and 2017. Patients were staged with CT, bone scintigraphy and/or PET/CT. From 2001 on, cN0M0 patients underwent staging laparoscopy. Ten patients had PM and were treated with CRS/HIPEC; 35 showed no metastases and underwent local treatment; 10 had distant metastases and received palliative chemotherapy. Disease-specific survival (DSS) rates were estimated using the Kaplan-Meier method and log-rank tests. Postoperative complications represent a secondary outcome., Results: The median follow-up was 96.8 months. Of the CRS/HIPEC patients, 5 (50%) developed a recurrence; 4 (40%) died of disease. The 2-yr and 5-yr DSS after CRS/HIPEC were 66.7% and 55.6%, respectively. DSS of the CRS/HIPEC patients did not significantly differ from DSS of patients without metastases who only underwent curative local treatment and was superior to patients with distant metastases (P = 0.012). The overall complication rate after CRS/HIPEC was 60%. Major complications (Clavien 3) constituted 20%. The study is limited by its retrospective nature and the small sample size., Conclusion: CRS/HIPEC demonstrates satisfactory long-term oncological outcome for patients with PM of UrAC. It may be offered as a potentially curative treatment option for this group of patients., (Copyright © 2019. Published by Elsevier Ltd.)

Purpose: To assess long-term functional and oncologic outcomes of prostate sparing cystectomy (PSC) as a sexuality-preserving alternative to radical cystectomy in a selected group of bladder cancer (BC) patients., Materials and Methods: Between 1995 and 2014, 185 BC patients underwent PSC according to one of two standardized procedures at two centers. All patients had received extensive evaluation to rule out prostate cancer and BC at the bladder neck and prostatic urethra (PU), including prostate specific antigen blood analysis, transrectal ultrasound and/or prostate biopsies, PU biopsies and/or PU frozen section analysis. All patients received an orthotopic ileal neobladder. Overall survival (OS) was assessed by Kaplan-Meier estimates. Cumulative incidence of cancer specific mortality, any recurrence and loco-regional recurrence were calculated using competing-risk methods. Finally, functional outcomes (voiding, continence and erectile function) were evaluated., Results: 185 patients (cTa-3N0M0) with a mean age of 57 years (SD: 9) were included. Median follow-up was 7.5 years (IQR: 5.6-10.8). Five-year OS was 71% and 5-year cumulative incidence of recurrence was 31%. Twenty patients (10.8%) had a loco-regional recurrence, two recurrences were in the PU. During follow-up, prostate cancer was detected in six patients (3.2%). Erectile function was preserved in 86.1% of patients, complete daytime and nighttime continence in 95.6% and 70.2%, respectively., Conclusion: This two-center study shows that in men with BC in whom the prostate and PU were proven free of malignancy, PSC would represent a valid treatment option with excellent functional outcome. Oncologic outcomes were comparable to what is known from radical cystoprostatectomy series., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Fibroblast growth factor receptor 3 (FGFR3) is an actionable target in bladder cancer. Preclinical studies show that anti-FGFR3 treatment slows down tumor growth, suggesting that this tyrosine kinase receptor is a candidate for personalized bladder cancer treatment, particularly in patients with mutated FGFR3. We addressed tumor heterogeneity in a large multicenter, multi-laboratory study, as this may have significant impact on therapeutic response., Patients and Methods: We evaluated possible FGFR3 heterogeneity by the PCR-SNaPshot method in the superficial and deep compartments of tumors obtained by transurethral resection (TUR, n = 61) and in radical cystectomy (RC, n = 614) specimens and corresponding cancer-positive lymph nodes (LN+, n = 201)., Results: We found FGFR3 mutations in 13/34 (38%) T1 and 8/27 (30%) ≥T2-TUR samples, with 100% concordance between superficial and deeper parts in T1-TUR samples. Of eight FGFR3 mutant ≥T2-TUR samples, only 4 (50%) displayed the mutation in the deeper part. We found 67/614 (11%) FGFR3 mutations in RC specimens. FGFR3 mutation was associated with pN0 (P < 0.001) at RC. In 10/201 (5%) LN+, an FGFR3 mutation was found, all concordant with the corresponding RC specimen. In the remaining 191 cases, RC and LN+ were both wild type., Conclusions: FGFR3 mutation status seems promising to guide decision-making on adjuvant anti-FGFR3 therapy as it appeared homogeneous in RC and LN+. Based on the results of TUR, the deep part of the tumor needs to be assessed if neoadjuvant anti-FGFR3 treatment is considered. We conclude that studies on the heterogeneity of actionable molecular targets should precede clinical trials with these drugs in the perioperative setting., (© The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Multiple bladder cancer studies report that the number of removed lymph nodes (lymph node count [LNC]) at radical cystectomy (RC) is positively associated with survival. Although these reports suggest that LNC can be used as a proxy for surgical quality, all studies used variable or inconsistent pelvic lymph node dissection (PLND) templates. We therefore wished to establish whether LNC at RC influences survival if surgeons adhere to a standardized PLND template., Materials and Methods: We included 274 patients who underwent RC from January 2005 until December 2012. All RCs were performed in either one of 2 hospitals (hospital A or B) by the same 4 urologists (all from hospital A) and a standardized PLND template was applied. PLND specimens were processed by 2 independent pathology departments (hospital A and B). We used Cox regression analysis to investigate the prognostic value of LNC adjusted for patient characteristics. We also compared LNC between hospitals and surgeons and investigated the effect of both the variables on overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS)., Results: Median LNC was 17 (interquartile range = 12). At a median follow-up of 64.3 months, there was no association between LNC and OS (P = 0.328), CSS (P = 0.645), or DFS (P = 0.450). Median LNC was higher in hospital B than in hospital A (20.0 vs. 16.0, P = 0.003). Median LNC varied significantly among surgeons (12-20, P<0.001). Neither the hospital of surgery nor the surgeon performing PLND influenced OS (P = 0.771 and P = 0.982, respectively), CSS (P = 0.310 and P = 0.691, respectively), or DFS (P = 0.256 and P = 0.296, respectively)., Conclusion: If surgeons adhere to a standardized template, LNC at RC does not affect long-term survival., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aim: To assess the results of a urinary diversion in patients who already have a colostomy or simultaneously require a (rectum) colon resection. The diversion is created from the distal part of the transected colon with a simultaneously created new colostomy contra-laterally (if necessary). This procedure is known in our institute as the 'colon shuffle'., Materials and Methods: All patients who underwent a colon shuffle in the period of 2003 and 2013 in our institute (Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital) were identified. Comorbidity was scored using the Charlson comorbidity index. Local or systemic treatment prior to surgery was reported (e.g. external beam radiotherapy, systemic chemotherapy). Surgical complications were reported according to the Clavien-Dindo classification., Results: Twenty-one patients (14 male; 7 female) underwent a colon shuffle procedure in our institute, with a mean age of 61.5 years. The majority (90.4%) of these patients had been subjected to radiotherapy on the pelvic region in the past. Although short-term complications (<30 days) were seen in 52.4% of these patients, major complications such as anastomotic leakage of the bowel and fecal peritonitis were not seen in this high-risk group of patients., Conclusion: The colon shuffle offers an elegant solution for patients who require a urinary diversion simultaneously with a colostomy or for patients who already have a colostomy from previous surgery., (Copyright © 2015 Elsevier Ltd. All rights reserved.)