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Objective: This study aimed to compare adverse in-hospital outcomes in ileal conduit versus neobladder urinary diversion type after radical cystectomy (RC) in contemporary versus historical patients., Methods: Patients were identified within the National Inpatient Sample (NIS 2000-2019). Propensity score matching (PSM; 1:2 ratio) and multivariable logistic regression models (LRMs) were used., Results: Of 10,533 contemporary (2011-2019) patients, 943 (9.0%) underwent neobladder urinary diversion, while 9590 (91.0%) underwent ileal conduit urinary diversion. Furthermore, of 9742 historical (2010-2019) patients, 932 (9.6%) underwent neobladder urinary diversion and 8810 (90.4%) underwent ileal conduit urinary diversion. After 1:2 PSM, within the contemporary cohort, 943/943 (100%) neobladder versus 1886/9590 (19.6%) ileal conduit patients were included. Similarly, within the historical cohort, 932/932 (100%) neobladder versus 1864/8810 (21.1%) ileal conduit patients were included after PSM. In multivariable LRMs, relative to contemporary neobladder patients, contemporary ileal conduit patients exhibited higher rates of overall postoperative (49.0 vs. 43.6%; multivariable odds ratio [MOR] 1.2), wound (4.2 vs. 2.7%; MOR 1.6), and genitourinary (13.1% vs. 10.0%; MOR 1.3) complications as well as blood transfusions (19.0 vs. 15.6%; MOR 1.3). Conversely, in multivariable LRMs within the historical cohort, no differences were recorded between ileal conduit and neobladder patients., Conclusions: Unlike historical comparisons between ileal conduit and neobladder patients, where no differences in adverse in-hospital outcomes were recorded, analyses relying on a contemporary patient cohort subject to PSM and multivariable adjustment revealed higher rates of adverse in-hospital outcomes in 4/13 examined categories. This observation should be considered at informed consent., (© 2024. Society of Surgical Oncology.)

Introduction: Neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) is guideline-recommended in patients with cT2-T4N0M0 urothelial carcinoma of urinary bladder (UCUB). However, no population-based study validated the survival benefit of NAC recorded in clinical trials in a stage-specific fashion. We addressed this knowledge gap., Methods: Within the Surveillance, Epidemiology, and End Results database (2007-2020), we identified patients with cT2-T4N0M0 UCUB treated with NAC before RC versus RC alone. Cumulative incidence plots and multivariable competing risks regression (CRR) models were fitted. Survival analyses were performed according to organ confined (OC: cT2N0M0) versus nonorgan confined stages (NOC: cT3-T4N0M0)., Results: Of 3,743 assessable patients, 1,020 (27%) underwent NAC versus 2,723 (73%) RC alone. NAC rates increased over time in OC stage (EAPC = 11.9%, P < 0.001) and NOC stage (EAPC = 8.6%, P < 0.001). In OC stage, cumulative incidence plots derived 5-year CSM was 15.6% in NAC and 19.9% in RC alone patients (P = 0.008). In multivariable CRR models, NAC independently predicted lower CSM (hazard ratio (HR): 0.74, P = 0.01). Similarly, in NOC stage, cumulative incidence plots derived 5-year CSM was 36.1% in NAC and 46.0% in RC alone patients (P = 0.01). In multivariable CRR models, NAC independently predicted lower CSM (HR: 0.66, P < 0.001)., Conclusion: NAC is associated with improved CSM compared to RC alone, both in OC and NOC stages. Specifically, the magnitude of the protective NAC effect was greater in NOC than OC patients. Thus, NAC should always be administered in all eligible patients before RC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

The overall survival (OS) improvement after the advent of several novel systemic therapies, designed for treatment of metastatic urothelial carcinoma of the urinary bladder (mUCUB), is not conclusively studied in either contemporary UCUB patients and/or non-UCUB patients. Within the Surveillance, Epidemiology, and End Results database, contemporary (2017-2020) and historical (2000-2016) systemic therapy-exposed metastatic UCUB and, subsequently, non-UCUB patients were identified. Separate Kaplan-Meier and multivariable Cox regression (CRM) analyses first addressed OS in mUCUB and, subsequently, in metastatic non-UCUB (mn-UCUB). Of 3443 systemic therapy-exposed patients, 2725 (79%) harbored mUCUB versus 709 (21%) harbored mn-UCUB. Of 2725 mUCUB patients, 582 (21%) were contemporary (2017-2020) versus 2143 (79%) were historical (2000-2016). In mUCUB, median OS was 11 months in contemporary versus 8 months in historical patients (Δ = 3 months; p < .0001). After multivariable CRM, contemporary membership status (2017-2020) independently predicted lower overall mortality (OM; hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.60-0.76; p < .001). Of 709 mn-UCUB patients, 167 (24%) were contemporary (2017-2020) and 542 (76%) were historical (2000-2016). In mn-UCUB, median OS was 8 months in contemporary versus 7 months in historical patients (Δ = 1 month; p = .034). After multivariable CRM, contemporary membership status (2017-2020) was associated with HR of 0.81 (95% CI = 0.66-1.01; p = .06). In conclusion, contemporary systemic therapy-exposed metastatic patients exhibited better OS in UCUB. However, the magnitude of survival benefit was threefold higher in mUCUB and approximated the survival benefits recorded in prospective randomized trials of novel systemic therapies., (© 2024 UICC.)

Objective: Systemic therapy is guideline-recommended for metastatic urothelial carcinoma of the urinary bladder (UCUB). Unmarried status represents an important barrier to treatment access in many primaries. The importance of married status is unknown in the context of systemic therapy in metastatic UCUB and was addressed in the current study., Methods: We relied on the Surveillance, Epidemiology, and End Results database (2004-2020) to identify patients with metastatic UCUB. Univariable and multivariable logistic regression models were fitted to address systemic therapy rates. Additionally, temporal trends were plotted., Results: Overall, 6873 patients with stage IV UCUB were identified. Of those, 4853 (71%) were male. Of males, 2993 (62%) were married vs. 797 (39%) of females. The rates of systemic therapy were 55% in both married males and married females. Married males and females differed from their unmarried counterparts regarding age and race/ethnicity. In males, prior to any adjustment, married status was associated with an odds ratio of 1.46 (P < .001). After adjustment for age and race/ethnicity, the odds ratio increased to 1.73 (P < .001). In females, prior to any adjustment, married status was associated with an odds ratio of 1.94 (P < .001). After adjustment for age and race/ethnicity, the odds ratio decreased to 1.57 (P < .001)., Conclusion: Unmarried males and unmarried females are significantly exposed to lower access to systemic therapy compared to their married counterparts. In consequence, both unmarried men and unmarried women should be given very careful consideration when use of systemic therapy in metastatic UCUB is contemplated., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To test the association between number as well as locations of organ-specific metastatic sites and overall survival (OS) in systhemic-therapy exposed metastatic urothelial carcinoma of urinary bladder (mUCUB) patients., Methods: Within Surveillance, Epidemiology and End Results database (2010-2020), all systhemic therapy-exposed mUCUB patients were identified. Kaplan-Meier and multivariable Cox regression (CRM) models first addressed OS in patients according to number of metastatic organ-locations: solitary versus 2 versus 3 or more. Subsequently, separate analyses stratified according to location type were completed in patients with solitary metastatic organ-location as well as in patients with 2 metastatic organ-locations., Results: Of 1,310 mUCUB, 1,069 (82%) harbored solitary metastatic organ-location versus 193 (15%) harbored 2 separate metastatic organ-locations versus 48 (3%) harbored 3 or more metastatic organ-locations. Median OS decreased with increasing number of metastatic organ-locations (solitary vs. 2 vs. 3 or more, P < .0001). In multivariable CRM, relative to solitary metastatic organ-location, 2 (HR: 1.57, 95 Confidence interval [CI], 1.33-1.85) as well as 3 or more (HR: 1.69, 95% CI, 1.23-2.31) metastatic organ-locations independently predicted higher overall mortality (OM) (P = .001). In patients with solitary metastatic organ-location, brain metastases independently predicted higher OM (HR 1.67; 95% CI, 1.05-2.67; P = .03) than other locations. In patients with 2 metastatic organ-locations, no differences in OM were recorded according to organ type location., Conclusion: In systemic therapy exposed mUCUB, number of metastatic organ-locations (solitary vs. 2 vs. 3 or more), independently predicted increasingly worse prognosis. In patients with solitary metastatic organ-location, brain purported worse prognosis than others., Competing Interests: Disclosure The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Administration of chemotherapy before radical cystectomy (RC) in neoadjuvant setting (NAC) or after RC in adjuvant setting (ADJ) are both associated with a survival benefit relative to RC alone. However, no study directly compared the magnitude of such benefit associated with NAC versus ADJ in locally-advanced UCUB patients (T3-T4N0M0). We addressed this knowledge gap., Methods: Within the Surveillance, Epidemiology, and End Results database (2007-2020), we identified T3-T4N0M0 UCUB patients who underwent NAC+RC or RC+ADJ. Cumulative incidence plots and multivariable competing risks regression (CRR) models were fitted. The same methodology was then re-applied in T3 and then T4 patient subgroups., Results: Of 875 assessable patients, 603 harbored T3 stage (69.0%) and 272 harbored T4 stage (31.0%). Of all 875, 563 (64.0%) underwent RC+ADJ versus 312 (36.0%) NAC+RC. NAC+RC rates increased over time (EAPC=+6.1%, P = .001). Cumulative incidence plots derived five-year CSM rates were 40.3% in NAC+RC versus 36.1% in RC+ADJ patients (P = .2). In multivariable CRR models that also adjusted for OCM, no statistically significant difference in CSM was recorded when NAC+RC was compared to RC+ADJ (HR:0.85, P = .1). Virtually the same observations were made in subgroup analyses where CSM associated with NAC+RC was not different from that recorded in RC+ADJ (HR: 0.89 and P = .4 in T3 stage and HR:0.8 and P = .2 in T4 stage)., Conclusion: In locally-advanced UCUB, NAC rates have sharply increased over time. However, the approach based on neoadjuvant chemotherapy prior to RC have not resulted in a statistically significant CSM benefit relative to RC+ADJ., Competing Interests: Disclosure None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To address cancer-specific mortality free-survival (CSM-FS) differences in patients with urothelial carcinoma of the urinary bladder (UCUB) vs non-UCUB who underwent trimodal therapy (TMT), according to organ confined (OC: T2N0M0) vs non-organ confined (NOC: T3-4NanyM0 or TanyN1-3M0) clinical stages., Patients and Methods: Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified patients with cT2-T4N0-N3M0 bladder cancer treated with TMT, defined as the combination of transurethral resection of bladder tumour, chemotherapy, and radiotherapy. Temporal trends described TMT use over time. Kaplan-Meier plots and multivariable Cox regression (MCR) models addressed CSM in UCUB vs non-UCUB according to OC vs NOC stages., Results: Of 5130 assessable TMT-treated patients, 425 (8%) harboured non-UCUB vs 4705 (92%) who had UCUB. The TMT rates increased for patients with OC UCUB from 92.4% to 96.8% (estimated annual percentage change of 0.4%, P < 0.001), but not in the NOC stages (P = 0.3). In the OC stage, the median CSM-FS was 36 months in patients with non-UCUB vs 60 months in those with UCUB, respectively (P = 0.01). Conversely, in the NOC stage, the median CSM-FS was 23 months both in UCUB and non-UCUB (P = 0.9). In the MCR models addressing OC stage, non-UCUB histology independently predicted higher CSM (hazard ratio 1.45, P = 0.004), but not in the NOC stage (P = 0.9)., Conclusion: In OC UCUB, TMT rates have increased over time in a guideline-consistent fashion. Patients with OC non-UCUB treated with TMT showed a CSM disadvantage relative to OC UCUB. In the NOC stage, use of TMT resulted in dismal CSM, regardless of UCUB vs non-UCUB histology., (© 2024 BJU International.)

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Introduction: Trimodal therapy (TMT) is guideline-recommended for the management of organ confined urothelial carcinoma of urinary bladder (UCUB). However, temporal trends in TMT use and cancer-specific mortality free-survival (CSM-FS) between historical TMT versus contemporary TMT have not been assessed. We addressed this knowledge gap., Material and Methods: Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified nonmetastatic UCUB patients with cT2-T4aN0-N2 treated with TMT, defined as the combination of transurethral resection of bladder tumor, chemotherapy and radiotherapy. Temporal trends described TMT use over time. Subsequently, patients were divided between historical (2004-2012) versus contemporary (2013-2020) cohorts. Survival analyses consisting of Kaplan-Meier plots and multivariable Cox regression (MCR) models addressed CSM-FS. Separate analyses addressed patients with organ confined (OC: cT2N0M0) versus nonorgan confined (NOC: cT3-4a and/or cN1-2) clinical stages., Results: Of 4,097 assessable UCUB TMT patients, 1744 (43%) were treated in the historical period (2004-2012) versus 2353 (58%) in the contemporary period (2013-2020). TMT use increased over time in OC patients (EAPC:+3.4%, P < .001), as well as in NOC (EAPC:+2.7%, P < .001). In OC stage, median CSM-FS was 55.3% in historical versus 49.0% in contemporary patients (HR:0.75, P < .001). Similarly, in NOC stage, 5-year median CSM-FS was 43.0% in historical versus 32.8% in contemporary patients (HR:0.78, P = .01)., Conclusion: TMT rates have increased over time in both OC and NOC patients. Contemporary TMT patients benefit of better cancer-specific survival. Interestingly, this benefit applies equally to OC and NOC TMT-treated patients., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: The study aims to report the feasibility and safety of palliative hypofractionated radiotherapy targeting macroscopic bladder tumors in a monocentric cohort of frail and elderly bladder cancer patients not eligible for curative treatments., Methods: Patients who underwent hypofractionated radiotherapy to the gross disease or to the tumor bed after transurethral resection of bladder tumor from 2017 to 2021 at the European Institute of Oncology IRCCS, were retrospectively considered. Schedules of treatment were 30 and 25 Gy in 5 fractions (both every other day, and consecutive days). Treatment response was evaluated with radiological investigation and/or cystoscopy. Toxicity assessment was carried out according to RTOG/EORTC v2.0 criteria., Results: A total of 16 patients were included in the study, of these 11 received hypofractionated radiotherapy on the macroscopic target volume and five on the tumor bed after transurethral resection of bladder tumor. No grade (G) >2 acute toxicities were described after treatment for both groups. Only one patient in the group receiving radiotherapy on the macroscopic disease reported G4 GU late toxicity. Ten patients had available follow-up status (median FU time 18 months), of them six had complete response, one had stable disease, and three had progression of disease. The overall response rate and disease control rate were 60% and 70%, respectively., Conclusion: Our preliminary data demonstrate that palliative hypofractionated radiotherapy for bladder cancer in a frail and elderly population is technically feasible, with an acceptable toxicity profile. These outcomes emphasize the potential of this approach in a non-radical setting and could help to provide more solid indications in this underrepresented setting of patients., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To assess in-hospital mortality and complication rates after radical cystectomy (RC) in patients with history of heart-valve replacement., Materials and Methods: Using the National Inpatient Sample (2000-2019), non-metastatic bladder cancer patients undergoing RC were stratified according to history of heart-valve replacement. Regression models (RM) predicted hospital outcomes., Results: Of 25,535 RC patients, 250 (1.0%) harbored history of heart-valve replacement. Heart-valve replacement patients were older (median 74 vs. 70 years), more frequently male (87.2 vs. 80.6%), and more frequently had Charlson comorbidity index ≥3 (26.8 vs. 18.9%). In RC patients with history of heart-valve replacement vs. others, 62 vs. 2634 (24.8 vs. 10.4%) experienced cardiac complications, 28 vs. 3092 (11.2 vs. 12.2%) intraoperative complications, 11 vs. 1046 (4.4 vs. 4.1%) infections, <11 vs. 594 (<4.4 vs. 2.3%) perioperative bleeding, <11 vs. 699 (<4.4 vs. 2.8%) vascular complications, 74 vs. 6225 (29.6 vs. 24.7%) received blood transfusions, 37 vs. 3054 (14.8 vs. 12.1%) critical care therapy (CCT), and in-hospital mortality was recorded in <11 vs. 463 (<4.4 vs. 1.8%) patients. In multivariable RM, history of heart-valve replacement independently predicted cardiac complications (odds ratio 2.20, 95% confidence interval 1.62-2.99; p < 0.001). Conversely, no statically significant association was recorded between history of heart-valve replacement and length of stay, estimated hospital cost, intraoperative complications, perioperative bleeding, vascular complications, infections, blood transfusions, CCT use, and in-hospital mortality., Conclusions: Radical cystectomy patients with history of heart-valve replacement exhibited a 2.2-fold higher risk of cardiac complications, but no other complications, including no significantly higher in-hospital mortality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Background: It is unknown whether regional differences in patient, tumor, and treatment characteristics of upper tract urothelial carcinoma (UTUC) patients exist and may potentially result in regional overall mortality (OM) differences. We tested for inter-regional differences, according to Surveillance, Epidemiology, and End Results (SEER) registries., Methods: Using SEER database 2000 to 2016, patient (age, sex, race/ethnicity), tumor (location, grade) and treatment (nephroureterectomy, systemic therapy [ST]) characteristics of UTUC patients of all-stages were tabulated and graphically depicted in a stage-specific fashion (T 1-2 N 0 M 0 vs. T 3-4 N 0 M 0 vs. T any N 1-2 M 0 /T any N any M 1 ). Multivariable Cox regression (MCR) models tested for inter-regional differences in OM., Results: Regarding T 1-2 N 0 M 0 patients, statistically significant differences existed for race/ethnicity (Caucasian 71 vs. 98%), location (renal pelvis: 55 vs. 67%), grade (high 60 vs. 83%) and ST (5.5 vs. 13.9%). In MCR models, registries 3 (Hazard ratio [HR]:1.39; P < 0.001) and 4 (HR:1.31; P = 0.01) independently predicted higher OM and Registry 8 (HR:0.64; P = 0.001) lower OM. Regarding T 3-4 N 0 M 0 patients, statistically significant differences existed for race/ethnicity (Caucasian 70 vs. 98%), location (renal pelvis: 67 vs. 76%), grade (high 84 vs. 94%) and ST (18.7 vs. 29.5%). In MCR models, registries 3 (HR:1.42; P < 0.001) and 4 (HR:1.31; P = 0.009) independently predicted higher OM. Regarding T any N 1-2 M 0 /T any N any M 1 patients, statistically significant differences existed for location (renal pelvis: 63 vs. 82%), grade (high 92 vs. 98%) and ST (53.4 vs. 58.8%). In MCR models, Registry 3 (HR:1.37; P = 0.004) independently predicted higher OM and Registry 2, (HR:0.78; P = 0.02) lower OM., Conclusions: Inter-regional differences were recorded in patients, tumor, and treatment characteristics. Even after adjustment for these characteristics, OM differences persisted which may be indicative of regional differences in quality of care or expertise in UTUC management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Upper tract urothelial carcinoma is rare but has a poor prognosis. Prognostic factors have been extensively studied in order to provide the best possible management for patients. We have aimed to investigate commonly available factors predictive of recurrence and survival in this patient population at high risk of death and recurrence, with an emphasis on the effects of age (using a cutoff of 70 years) on survival outcomes., Patients and Methods: From 1387 patients with clinically nonmetastatic upper tract urothelial carcinoma treated with radical nephroureterectomy at 21 academic hospital centers between 2005 and 2021, 776 patients were eligible and included in the study. Univariable and multivariable Cox regression models were built to evaluate the independent prognosticators for intravesical and extravesical recurrence, overall survival, and cancer-specific survival according to age groups. A P value of <.05 was considered statistically significant., Results: We did not find an association between groups aged <70 and >70 years old and preoperatively clinical or histopathological characteristics. Kaplan-Meier analysis was found no statistical significance between the 2 age groups in terms of intravesical or extravesical recurrence (P = .09 and P = .57). Overall survival (P = .0001) and cancer-specific survival (P = .0001) have been found to be statistically significantly associated with age as independent predictors (confounding factors: gender, tumor size, tumor side, clinical T stage, localization, preoperative hydronephrosis, tumor localization, type of surgery, multifocality of the tumor, pathological grade, lymphovascular invasion, concomitant CIS, lymph node status, necrosis, or history of previous bladder cancer)., Conclusion: This research confirms that patients aged 70 and above who undergo radical nephroureterectomy may have worse outcomes compared to younger patients, older patients needing an improved care and management of UTUC to improve their outcomes in the setting of an increase in this aged population group., (Copyright © 2023 Elsevier Inc. All rights reserved.)

To the Editor, Bladder cancer is one of the most common cancers in humans, representing the 7th and 17th type of neoplasm in both genders. Its incidence and mortality are quite heterogeneous in different countries and are due to different risk factors, quality and prevalence of healthcare and the possibility of early diagnosis and treatment of the tumor and its potential recurrences [...].

Background: In patients affected by high-risk nonmuscle invasive bladder cancer (HR-NMIBC) progression to muscle invasive status is considered as the main indicator of local treatment failure. We aimed to investigate the effect of progression and time to progression on overall survival (OS) and to investigate their validity as surrogate endpoints., Methods: A total of 1,510 patients from 18 different institutions treated for T1 high grade NMIBC, followed by a secondary transurethral resection and BCG intravesical instillation. We relied on random survival forest (RSF) to rank covariates based on OS prediction. Cox's regression models were used to quantify the effect of covariates on mortality., Results: During a median follow-up of 49.0 months, 485 (32.1%) patients progressed to MIBC, while 163 (10.8%) patients died. The median time to progression was 82 (95%CI: 78.0-93.0) months. In RSF time-to-progression and age were the most predictive covariates of OS. The survival tree defined 5 groups of risk. In multivariable Cox's regression models accounting for progression status as time-dependent covariate, shorter time to progression (as continuous covariate) was associated with longer OS (HR: 9.0, 95%CI: 3.0-6.7; P < 0.001). Virtually same results after time to progression stratification (time to progression ≥10.5 months as reference)., Conclusion: Time to progression is the main predictor of OS in patients with high risk NMIBC treated with BCG and might be considered a coprimary endpoint. In addition, models including time to progression could be considered for patients' stratification in clinical practice and at the time of clinical trials design., Competing Interests: Declaration of competing interest Each of the authors certify that the manuscript represents original and valid work that has not been previously published and is not currently under consideration by any other journal. Additionally, all the authors: have given final approval of the submitted manuscript approved the contents of this paper and have participated sufficiently in the work to take public responsibility for all content. None of the contributing authors have any conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript. No funding or other financial support was received., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Accurate visual classification of bladder tissue during Trans-Urethral Resection of Bladder Tumor (TURBT) procedures is essential to improve early cancer diagnosis and treatment. During TURBT interventions, White Light Imaging (WLI) and Narrow Band Imaging (NBI) techniques are used for lesion detection. Each imaging technique provides diverse visual information that allows clinicians to identify and classify cancerous lesions. Computer vision methods that use both imaging techniques could improve endoscopic diagnosis. We address the challenge of tissue classification when annotations are available only in one domain, in our case WLI, and the endoscopic images correspond to an unpaired dataset, i.e. there is no exact equivalent for every image in both NBI and WLI domains., Method: We propose a semi-surprised Generative Adversarial Network (GAN)-based method composed of three main components: a teacher network trained on the labeled WLI data; a cycle-consistency GAN to perform unpaired image-to-image translation, and a multi-input student network. To ensure the quality of the synthetic images generated by the proposed GAN we perform a detailed quantitative, and qualitative analysis with the help of specialists., Conclusion: The overall average classification accuracy, precision, and recall obtained with the proposed method for tissue classification are 0.90, 0.88, and 0.89 respectively, while the same metrics obtained in the unlabeled domain (NBI) are 0.92, 0.64, and 0.94 respectively. The quality of the generated images is reliable enough to deceive specialists., Significance: This study shows the potential of using semi-supervised GAN-based bladder tissue classification when annotations are limited in multi-domain data.

Purpose: To evaluate the association between radical cystectomy (RC) and cancer-specific mortality (CSM) in patients diagnosed with adenocarcinoma of the bladder (ACB). Moreover, to directly compare the survival advantage of RC between ACB vs. urothelial bladder cancer (UBC)., Materials and Methods: Non-metastatic muscle-invasive ACB and UBC patients were identified within Surveillance, Epidemiology, and End Results database (SEER 2000-2018). All analyses were stratified between RC vs. no-RC, in either organ-confined (OC: T 2 N 0 M 0 ) or non-organ-confined (NOC: T 3-4 N 0 M 0 or T any N 1-3 M 0 ) stages. Propensity score matching (PSM), cumulative incidence plots, competing risks regression (CRR) analyses, and 3 months' landmark analyses were performed., Results: Overall, 1,005 ACB and 47,741 UBC patients were identified, of whom 475 (47%) and 19,499 (41%) were treated with RC, respectively. After PSM, comparison between RC vs. no-RC applied to 127 vs. 127 OC-ACB, 7,611 vs. 7,611 OC-UBC, 143 vs. 143 NOC-ACB, and 4,664 vs. 4,664 NOC-UBC patients. 36-month CSM rates in RC vs. no-RC patients were 14 vs. 44% in OC-ACB, 18 vs. 39% in OC-UBC, 49 vs. 66% in NOC-ACB, and 44 vs. 56% in NOC-UBC patients. In CRR analyses, the effect of RC on CSM yielded a hazard ratio of 0.37 in OC-ACB, of 0.45 in OC-UBC, of 0.65 in NOC-ACB and of 0.68 in NOC-UBC patients (all P values<0.001). Landmark analyses virtually perfectly replicated the results., Conclusions: In ACB, regardless of stage, RC is associated with lower CSM. The magnitude of this survival advantage was greater in ACB than in UBC, even after control for immortal time bias., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: It is unknown to what extent overall survival (OS) of organ-confined (T2N0M0) urothelial carcinoma of the urinary bladder (UCUB) patients differs from age- and sex-matched population-based controls, especially when treatment modalities such as radical cystectomy (RC), trimodal therapy (TMT), or radiotherapy (RT) are considered., Methods: Relying on the Surveillance Epidemiology and End Results database (2004-2018), we identified newly diagnosed (2004-2013) T2N0M0 UCUB patients treated with either RC, TMT or RT. For each case, we simulated an age- and sex-matched control (Monte Carlo simulation), relying on Social Security Administration Life Tables with 5 years of follow-up, and compared OS with that of RC-, TMT-, and RT-treated cases. Additionally, we relied on smoothed cumulative incidence plots to display cancer-specific mortality (CSM) and other-cause mortality (OCM) rates for each treatment modality., Results: Of 7153 T2N0M0 UCUB patients, 4336 (61%) underwent RC, 1810 (25%) TMT, and 1007 (14%) RT. At 5 years, OS rate in RC cases was 65% vs. 86% in population-based controls (Δ = 21%); in TMT cases, 32% vs. 74% in population-based controls (Δ = 42%); and in RT, 13% vs. 60% in population-based control (Δ = 47%). Five-year CSM rates were highest in RT (57%), followed by TMT (46%) and RC (24%). Five-year OCM rates were the highest in RT (30%), followed by TMT (22%) and RC (12%)., Conclusion: OS of T2N0M0 UCUB patients is substantially less than that of age- and sex-matched population-based controls. The biggest difference affects RT, followed by TMT. A modest difference was recorded in RC and population-based controls., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Recently, the European Association of Urology Guidelines Panel updated the prognostic factor risk groups model for non-muscle-invasive bladder cancer (NMIBC) with the introduction of a new group of patients at very high risk (VHR). Furthermore, three additional clinical risk factors (i.e., age>70 years, multiple papillary tumors; tumor diameter >3 cm) were proposed. However, the new scoring model was created by analyzing data from patients who did not receive BCG intravesical therapy., Methods: This is a retrospective multicenter study analyzing data of 920 patients with HGT1 NMIBC that underwent ReTUR e following BCG intravesical therapy. Patients were stratified into risk groups according to the 2021 new EAU NMIBC prognostic factor risk groups model. This study aimed to identify variables related to disease progression in a large cohort of HGT1 NMIBC patients who underwent both Re-TURB and BCG intravesical immunotherapy., Results: Median follow-up was 51 months (IQR 41-75), according to EAU NMIBC 2021 scoring model 179 (19.5%) patients were at VHR. Progression-free survival at 5 years was 68.2% and 59.9% for the whole sample and the VHR group, respectively. At multivariable regression model size >3 cm, multifocal tumor, concomitant CIS and LVI were identified as independently associated with disease progression., Conclusions: Although patients at VHR are more likely to experience disease progression during follow-up, the European Association of Urology (EAU) NMIBC 2021 scoring model appears to be suboptimal in patients who underwent ReTUR and intravesical BCG therapy.

Purpose: To assess the effect of event-free survival duration on cancer-specific mortality (CSM) after radical cystectomy (RC) in nonmetastatic muscle-invasive squamous cell carcinoma of the urinary bladder., Methods: RC patients treated for non-metastatic muscle-invasive squamous cell carcinoma of the urinary bladder were identified within the Surveillance, Epidemiology, and End Results database (2000-2018). Independent predictor status for CSM of T and N stage groupings (i.e., T2N0, T3N0, T4N0, and TanyN1-3) was tested in multivariable Cox-regression models. Conditional 5-year CSM-free estimates were assessed at baseline and at 4 specific event-free survival times (i.e. 6, 12, 18 and 24 months), within each of the 4 examined stage groups., Results: Of 981 RC patients, 206 (21%), 416 (42%), 152 (16%), and 207 (21%) were T2N0, T3N0, T4N0, and TanyN1-3, respectively. In multivariable Cox-regression models T3N0 (HR 1.94), T4N0 (HR 5.22), and TanyN1-3 (HR 6.62) were independent predictors of CSM, relative to T2N0. In conditional survival analyses based on 24 months event-free status, survival estimates were: 89% for T2N0 vs. 76% at baseline (Δ = 13%), 84% for T3N0 vs. 58% at baseline (Δ = 26%), 69% for T4N0 vs. 25% at baseline (Δ = 44%), 69% for TanyN1-3 vs. 22% at baseline (Δ = 47%)., Conclusions: Event-free status at 24 months of follow-up is associated with substantially higher CSM-free survival than when CSM-free survival is predicted at baseline. The magnitude of this effect is most pronounced in TanyN1-3 and T4N0 patients, intermediate in T3N0 and more modest, nonetheless important, in T2N0., Competing Interests: Conflict of interest This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors declare no conflicts of interest in preparing this article., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: The effect of radical cystectomy (RC) on cancer-specific mortality (CSM) is unclear in non-metastatic sarcomatoid bladder cancer (SBC) patients. We aimed to test the benefit of RC in SBC, and to perform a direct comparison vs urothelial bladder cancer (UCB)., Materials and Methods: Within the Surveillance, Epidemiology, and End Results database (SEER 2001-2018) all non-metastatic SBC and UBC patients were identified. Endpoint of interest was CSM. Propensity score matching (PSM), cumulative incidence plots, competing risks regression (CRR) analyses, three-months landmark analyses, and sensitivity analyses were performed. All results were stratified according to organ-confined (OC: T 2 N 0 M 0 ) vs non-organ-confined (NOC: T 3-4 N 0 M 0 or T any N 1-3 M 0 ) stages., Results: Of 554 SBC patients, 49 vs 51% harbored OC vs NOC stages. Of 47,741 UBC patients, 62 vs 38% harbored OC vs NOC stages. RC rates were 33 vs 67% in OC vs NOC-SBC patients, and 40 vs 60% in OC vs NOC-UBC patients. After 1:1 PSM, comparison between RC vs no-RC was performed in OC-SBC (67 patients per group), OC-UBC (7611 patients per group), NOC-SBC (63 patients per group), and NOC-UBC patients (4644 patients per group). CRR hazard ratios associated with RC vs no-RC were 0.37 (p < 0.001) in OC-SBC vs 0.45 (p < 0.001) in OC-UBC, and 0.56 (p = 0.01) in NOC-SBC vs 0.68 (p < 0.001) in NOC-UBC. These results were replicated in sensitivity and landmark analyses., Conclusions: The protective effect of RC vs no-RC is stronger in SBC than UBC patients, regardless of OC vs NOC stages., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interests., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

A trend towards greater benefit from adjuvant chemotherapy (ACT) in pN+ bladder cancer (BCa) has been observed in multiple randomized controlled trials. However, it is still unclear which patients might benefit the most from this approach. We retrospectively analyzed a multicenter cohort of 1381 patients with pTany pN1-3 cM0 R0 urothelial BCa treated with radical cystectomy (RC) with or without cisplatin-based ACT. The main endpoint was overall survival (OS) after RC. We performed 1:1 propensity score matching to adjust for baseline characteristics and conducted a classification and regression tree (CART) analysis to assess postoperative risk groups and Cox regression analyses to predict OS. Overall, 391 patients (28%) received cisplatin-based ACT. After matching, two cohorts of 281 patients with pN+ BCa were obtained. CART analysis stratified patients into three risk groups: favorable prognosis (≤pT2 and positive lymph node [PLN] count ≤2; odds ratio [OR] 0.43), intermediate prognosis (≥pT3 and PLN count ≤2; OR 0.92), and poor prognosis (pTany and PLN count ≥3; OR 1.36). Only patients with poor prognosis benefitted from ACT in terms of OS (HR 0.51; p < 0.001). We created the first algorithm that stratifies patients with pN+ BCa into prognostic classes and identified patients with pTany BCa with PLN ≥3 as the most suitable candidates for cisplatin-based ACT. PATIENT SUMMARY: We found that overall survival among patients with bladder cancer and evidence of lymph node involvement depends on cancer stage and the number of positive lymph nodes. Patients with more than three nodes affected by metastases seem to experience the greatest overall survival benefit from cisplatin-based chemotherapy after bladder removal. Our study suggests that patients with the highest risk should be prioritized for cisplatin-based chemotherapy after bladder removal., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: Seventy-five percent of bladder cancers are non-muscle invasive. The treatment strategy includes the transurethral resection of bladder tumor (TURB) followed by intravesical immunotherapy with the bacillus of Calmette-Guerin (BCG) or chemotherapy, depending on the grade of bladder tumor. Despite a proper BCG intravesical instillations schedule, up to 40% of patients present a failure within 2 years. The aim of this retrospective study was to investigate the predictive factors in the response to BCG in patients with a high-grade non-muscle invasive bladder cancer diagnosis., Materials and Methods: Patients with non-muscle invasive bladder cancer from 13 hospitals and academic institutions were identified and treated, from January 1, 2002, until December 31, 2012, with TURB and a subsequent re-TURB for restaging before receiving BCG. Follow-up was performed with urine cytology and cystoscopy every 3 months for 1 year and, successively every 6 months. Univariate and multivariate Cox regression models addressed the response to BCG therapy. Kaplan-Meier overall survival (OS) and cancer-specific survival (CSS) estimates were determined for BCG responsive vs. BCG unresponsive patients., Results: A total of 1,228 patients with non-muscle invasive bladder cancer were enrolled. Of 257 (20.9%) patients were BCG unresponsive. Independent predictive factors for response to BCG were: multifocality (HR: 1.4; 95% CI 1.05-1.86; P = 0.019), lymphovascular invasion (HR: 1.75; 95% CI 1.22-2.49; P = 0.002) and high-grade on re-TURB (HR: 1.39; 95% CI 1.02-1.91; P = 0.037). Overall survival was significantly reduced in BCG-unresponsive patients compared to BCG-responsive patients at 5 years (82.9% vs. 92.4%, P < 0.0001) and at 10 years (44.2% vs. 74.4%, P < 0.0001). Similarly, cancer-specific survival was reduced in BCG-unresponsive patients at 5 years (90.6% vs. 97.3%, P < 0.0001) and at 10 years (72.3% vs. 87.2%, P < 0.0001)., Conclusion: Multifocality, lymphovascular invasion, and high-grade on re-TURB were independent predictors for response to BCG treatment. BCG-unresponsive patients reported worse oncological outcomes., Competing Interests: Conflict of interests The authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To investigate prevalence and predictors of renal function variation in a multicenter cohort treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC)., Methods: Patients from 17 tertiary centers were included. Renal function variation was evaluated at postoperative day (POD)-1, 6 and 12 months. Timepoints differences were Δ1 = POD-1 eGFR - baseline eGFR; Δ2 = 6 months eGFR - POD-1 eGFR; Δ3 = 12 months eGFR - 6 months eGFR. We defined POD-1 acute kidney injury (AKI) as an increase in serum creatinine by ≥ 0.3 mg/dl or a 1.5 1.9-fold from baseline. Additionally, a cutoff of 60 ml/min in eGFR was considered to define renal function decline at 6 and 12 months. Logistic regression (LR) and linear mixed (LM) models were used to evaluate the association between clinical factors and eGFR decline and their interaction with follow-up., Results: A total of 576 were included, of these 409(71.0%) and 403(70.0%) had an eGFR < 60 ml/min at 6 and 12 months, respectively, and 239(41.5%) developed POD-1 AKI. In multivariable LR analysis, age (Odds Ratio, OR 1.05, p < 0.001), male gender (OR 0.44, p = 0.003), POD-1 AKI (OR 2.88, p < 0.001) and preoperative eGFR < 60 ml/min (OR 7.58, p < 0.001) were predictors of renal function decline at 6 months. Age (OR 1.06, p < 0.001), coronary artery disease (OR 2.68, p = 0.007), POD-1 AKI (OR 1.83, p = 0.02), and preoperative eGFR < 60 ml/min (OR 7.80, p < 0.001) were predictors of renal function decline at 12 months. In LM models, age (p = 0.019), hydronephrosis (p < 0.001), POD-1 AKI (p < 0.001) and pT-stage (p = 0.001) influenced renal function variation (ß 9.2 ± 0.7, p < 0.001) during follow-up., Conclusion: Age, preoperative eGFR and POD-1 AKI are independent predictors of 6 and 12 months renal function decline after RNU for UTUC., (© 2022. The Author(s).)

Purpose: To compare the outcomes of robotic radical nephroureterectomy (RRNU) and laparoscopic radical nephroureterectomy (LRNU) within a large multi-institutional worldwide dataset. Materials and Methods: The ROBotic surgery for Upper tract Urothelial cancer STudy (ROBUUST) includes data from 17 centers worldwide regarding 877 RRNU and LRNU performed between 2015 and 2019. Baseline features, perioperative and oncologic outcomes, were included. A 2:1 nearest-neighbor propensity-score matching with a 0.001 caliper was performed. A univariable and a multivariable logistic regression model were built to evaluate the predictors of a composite "tetrafecta" outcome defined as occurrence of bladder cuff excision+LND+no complications+negative surgical margins. Results: After matching, 185 RRNU and 91 LRNU were assessed. Patients in the RRNU group were more likely to undergo bladder cuff excision (81.9% vs 63.7%; p  < 0.001) compared to the LRNU group. A statistically significant difference was found in terms of overall postoperative complications ( p  = 0.003) and length of stay ( p  < 0.001) in favor of RRNU. Multivariable analysis demonstrated that LRNU was an independent predictor negatively associated with achievement of "tetrafecta" (odds ratio: 0.09; p  = 0.003). Conclusions: In general, RRNU and LRNU offer comparable outcomes. While the rate of overall complications is higher for LRNU in this study population, this is mostly related to low-grade complications, and therefore with more limited clinical relevance. RRNU seems to offer shorter hospital stay, but this might also be related to the different geographical location of participating centers. Overall, the implementation of robotics might facilitate achievement of a "tetrafecta" outcome as defined in the present study.

Objective: To compare the accuracy in detecting variant histologies (VH) at transurethral resection of bladder (TURB) and radical cystectomy (RC) specimen among tertiary referral centres, in order to investigate potential reasons of discrepancies from the pathological point of view., Patients and Methods: Clinical and histopathological data of TURB specimen and subsequent cystectomy specimen of 3,445 RC candidate patients have been retrospectively collected from 24 tertiary referral centres between 1980 and 2021. VH considered in the analysis were pure squamous cell carcinoma, urothelial carcinoma with squamous differentiation, pure adenocarcinoma, urothelial carcinoma with glandular differentiation, micropapillary bladder cancer (BCa), neuroendocrine BCa, and other variants. The degree of agreement between TURB and RC concerning the identification of VH was expressed as concordance, classified according to Cohen's kappa coefficient., Results: A VH was reported in 17% of TURB specimens, 45% of which were not confirmed in RC. The lowest concordance rate was reported for micropapillary BCa with 11 out of 18 (61%) centres reporting no agreement, whereas neuroendocrine BCa achieved the highest concordance rate with only 3 centres (17%) reporting no agreement. Our results shows that even among centres with the advantage of a referent uropathologist the micropapillary variant is characterized by scarce accuracy between TURB and RC. Differences in TURB specimen acquisition by the urologist and in sampling methods among different centres are the main limitations of the study., Conclusions: Accuracy of TURB in detecting VH is poor for certain VH, in particular for micropapillary BCa, with evident variation among centres. Novel diagnostic tools are required to better identify these VH and drive patients toward a personalized treatment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To test the impact of carboplatin-based ACT on overall survival (OS) in patients with pN1-3 cM0 BCa., Methods: A retrospective analysis was conducted on 1057 patients with pTany pN1-3 cM0 urothelial BCa treated with or without carboplatin-based ACT after radical cystectomy and bilateral lymph-node dissection between 2002 and 2018 at 12 European and North-American hospitals. No patient received neoadjuvant chemotherapy or radiation therapy. Only patients with negative surgical margins at surgery were included. A 3:1 propensity score matching (PSM) was performed using logistic regression to adjust for baseline characteristics. Univariable and multivariable Cox regression analyses were used to predict the effect of carboplatin-based ACT on OS. The Kaplan-Meier method was used to display OS in the matched cohort., Results: Of the 1057 patients included in the study, 69 (6.5%) received carboplatin-based ACT. After PSM, 244 total patients were identified in two cohorts that did not differ for baseline characteristics. Death was recorded in 114 (46.7%) patients over a median follow-up of 19 months. In the multivariable Cox regression analyses, increasing age at surgery (hazard ratio [HR] 1.02, 95% confidence interval [CI] 1.01-1.06, p < 0.001) and increasing number of positive lymph nodes (HR 1.06, 95% CI 1.01-1.07, p = 0.02) were independent predictors of worse OS. The delivery of carboplatin-based ACT was not predictive of improved OS (HR 0.67, 95% CI 0.43-1.04, p = 0.08). The main limitations of this study are its retrospective design and the relatively low number of patients involved., Conclusions: Carboplatin-based might not improve OS in patients with pN1-3 cM0 BCa. Our results underline the need for alternative therapies for cisplatin-ineligible patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The preoperative lymph node (LN) staging of bladder cancer (BCa) addresses the subsequent therapeutic strategy and influences patient's prognosis. However, sparce evidence exists regarding the accuracy of conventional cross-sectional imaging, such as computed tomography or magnetic resonance imaging, in correctly detect LN status. We aimed to assess the diagnostic accuracy of conventional cross-sectional imaging in detecting preoperative LN involvement among BCa patients treated with radical cystectomy and pelvic lymph node dissection., Methods: We retrospectively analyzed data of 1,104 patients who underwent preoperative LN staging with computed tomography or magnetic resonance imaging and subsequent radical cystectomy with pelvic lymph node dissection for BCa between 1997 and 2017 at three tertiary referral centers. Patients receiving neoadjuvant chemotherapy were excluded. We assessed the concordance between clinical (cN) and pathological LN (pN) status, defined as the accuracy of imaging in detecting LN involvement using pathological specimen as reference; concordance was expressed according to Cohen's kappa coefficient. Location-based sub-analyses were performed, distinguishing among external iliac, intern iliac, obturator, common iliac, presacral and paraaortic LNs., Results: Among 870 cN0 patients, 68.9% were confirmed pN0 at pathological report; while among 234 cN+ patients, 50.5% were found with LN metastases at pathological specimen. Overall, conventional imaging showed slight concordance (64.9%) between cN and pN stages (sensitivity: 30%; specificity: 84%). At sub-analysis, no agreement between cN and pN status was found in each LN location, with the only exception of common iliac LNs with slight concordance (37.5%). Common iliac LNs achieved the highest sensitivity and positive likelihood ratio (15% and 2.4, respectively) compared to other LN locations., Conclusions: Overall, preoperative cross-sectional imaging exhibited a slight concordance between cN and pN status. Our location-based sub-analyses showed unsatisfactory results in each LN location- Thus, nomograms combining morphological patterns with serological and clinicopathological features are urgently required., Competing Interests: Conflict of interest disclosure None declared., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: The aim of this multicenter study was to investigate the role of age (cut-off 70 years) at diagnosis in predicting oncologic behavior of pure carcinoma in situ of the bladder., Material and Methods: Inclusion criteria were: patients with pure CIS confirmed and that followed intravesical BCG treatment. Pure CIS was defined at any CIS not associated with another urothelial cancer. Exclusion criteria were: any CIS associated with invasive urothelial carcinoma. A total of 172 with pure CIS treated between January 1, 2002 and December 31, 2012 at 8 academic institutions met the inclusion criteria. The maintenance schedule was generally according to the EAU guidelines at the time RESULTS: A total of 99 (57.6%) patients had an age >70 years prior to TURBT. There was no difference between clinico-pathologic features among groups (group 1, age ≤ 70 years and group 2, age > 70 years), except that patients aged ≤ 70 years presented a larger size of CIS (35.6% vs. 21.2%), P = .02. In multivariable Cox regression analyses, the same clinico-pathologic factors (age, multifocality, and recurrent tumor state) were independently associated with worse RFS. Harrell's C-index was 65.75.In multivariable Cox regression analyses in addition to age (P = .006) and multifocality (P < .001) also BMI (P = .04) was independently associated with worse PFS. Harrell's C-index was 74.71 CONCLUSION: Advanced age at diagnosis appears to be associated with an increased risk of recurrence and progression of pure carcinoma in situ of the bladder. Elderly patients might fail to respond to BCG therapy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Correct identification of variant histologies (VHs) of bladder cancer (BCa) at transurethral resection of the bladder (TURB) could drive the subsequent treatment., Objective: To evaluate the concordance in detecting VHs between TURB and radical cystectomy (RC) specimens in BCa patients., Design, Setting, and Participants: We retrospectively analyzed 1881 BCa patients who underwent TURB and subsequent RC at seven tertiary care centers between 1980 and 2018. VHs were classified as sarcomatoid, lymphoepithelioma-like, neuroendocrine, squamous, micropapillary, glandular, adenocarcinoma, nested, and other variants., Outcome Measurements and Statistical Analysis: Concordance between TURB and RC was defined as the ability to achieve histological subtypes at TURB confirmed at RC specimen, and was expressed according to Cohen's kappa coefficient., Results and Limitations: Of the patients, 14.6% and 21% were diagnosed with VH at TURB and RC specimens, respectively. The most common VHs at TURB were squamous, neuroendocrine, and micropapillary carcinoma (5.2%, 1.5%, and 1.5%, respectively). At RC, the most frequent VHs were squamous, micropapillary, and sarcomatoid carcinoma (7.2%, 3.0%, and 2.7%, respectively). The overall concordance in detecting VH was defined as slight concordance (coefficient: 0.18). Moderate concordance was found for neuroendocrine, adenocarcinoma, and squamous carcinoma (coefficient: 0.49, 0.47, and 0.41, respectively). Micropapillary, glandular, and other variants showed slight concordance (coefficient: 0.05, 0.17, and 0.12, respectively), while nested and sarcomatoid carcinoma showed fair concordance (coefficient: 0.32 and 0.26, respectively). Results may be limited by the absence of centralized pathological analysis., Conclusions: A non-negligible percentage of patients were diagnosed with VH at both TURB and RC. TURB showed relatively low accuracy, ranging from poor to moderate, in detecting VHs. Our study underlines the need of additional diagnostic tools in order to identify VHs properly at precystectomy time and to improve patient survival outcomes., Patient Summary: In this report, we underlined the low accuracy of transurethral resection of the bladder in detecting variant histologies and the need for additional diagnostic tools., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: This study reports the safety and efficacy of Oncofid - P-B, a novel compound under development by Fidia Farmaceutici S.p.A. with specific binding to CD44 receptor, in patients with CIS unresponsive or intolerant to BCG., Materials and Methods: This is a phase 1 open-label, single arm, multicenter European study to assess safety, tolerability and efficacy of Oncofid-P-B administered in 20 patients with CIS ± Ta-T1, unresponsive or intolerant to BCG, unwilling or unfit for cystectomy. Oncofid-P-B was administered by intravesical instillation for 12 consecutive weeks (intensive phase) followed, in CR patients, by 12 monthly instillations (maintenance phase). The primary objective was the overall safety profile. Secondary objectives included: i) any evidence of antitumor activity, ii) patient's compliance, iii) systemic absorption. The CR was defined as a negative cystoscopy, negative biopsy of the urothelium and negative cytology., Results: At the end of the intensive phase, 15 of the 20 enrolled patients (75%), achieved the CR. Patients still in CR after 3, 6, 9 and 12 months of maintenance phase were 13 (65%), 12 (60%), 9 (45%) and 8 (40%), respectively. Only seven (5 mild and 2 moderate) drug-related AEs were reported in three patients. No drug related serious AEs and no drug related withdrawals have been reported. In all plasma samples, the drug concentratiosn was below the LLOQ (1ng/ml)., Conclusions: Oncofid-P-B is very safe, well tolerated and highly effective (75% CR) when administered weekly for up to 12 consecutive weeks (75% CR), with 40% CR still after 15 months from treatment start., (Copyright © 2021. Published by Elsevier Inc.)

Background: We aimed to test the hypothesis that the immune-modulatory effect of statins may improve survival outcomes in patients with non-muscle invasive bladder cancer (NMIBC). We focused on a cohort of patients diagnosed with high risk NMIBC, that were treated with intravesical BCG immunotherapy., Methods: We included patients at first diagnosis of T1 high grade NMIBC after transurethral resection of bladder (TURB). All procedures were performed at 18 different tertiary institutions between January 2002 and December 2012. Univariable and multivariable models were used to test differences in terms of residual tumor, disease recurrence, disease progression and overall mortality (OM) rates., Results: Overall, 1510 patients with T1 high grade NMIBC at TURB were included in our analyses. Of these, 402 (26.6%) were statin users. At multivariable analysis, statin use was associated with a higher rate of high-grade BC at re-TURB (OR: 1.37, 95%CI: 1.04-1.78; P=0.022), while at follow-up it was not independently associated with OM (HR: 0.71, 95%CI: 0.50-1.03; P=0.068) and disease progression rates (HR: 0.97, 95%CI: 0.79-1.19; P=0.753). Conversely, statin use has been shown to be independently associated with a lower risk of recurrence (HR:0.80, 95%CI: 0.67-0.95; P=0.009). The median recurrence-free survival was 47 (95%CI 40-49) months for those classified as non-statin users vs. 53 (95%CI 48-68) months in those classified as statin users., Conclusions: Statin daily intake do not compromise oncological outcomes in high risk NMIBC patients treated with BCG. Moreover, statin may have a beneficial effect on recurrence rates in this cohort of patients.

The objective of the current research was to explore the potential prognostic value of readily available clinical and pathologic variables in bladder cancer. The novel association found between cholesterol levels and prognosis may provide the rationale for exploring novel treatments. Patients included had histologically confirmed urothelial bladder cancer and were treated with at least 3 cycles of cisplatin-based neoadjuvant chemotherapy before radical cystectomy with lymphadenectomy. A total of 245 patients at low, intermediate and high risk, presenting with 0-1, 2 or 3-4 risk factors, including positive lymph nodes, Hb <12.8, NLR ≥2.7 and cholesterol levels ≥199, were included. Five-year cancer-specific survival rate was 0.67, 0.78 and 0.94 at high, intermediate and low risk, respectively. Total cholesterol levels at the time of cystectomy may represent a commonly assessable prognostic factor and may be incorporated in a clinically meaningful risk-group classification model.

Purpose: Presently, major guidelines do not provide specific recommendations on oncologic surveillance for patients who harbor variant histology (VH) bladder cancer (BCa) at radical cystectomy. We aimed to create a personalized followup scheme that dynamically weighs other cause mortality (OCM) vs the risk of recurrence for VH BCa, and to compare it with a similar one for pure urothelial carcinoma (pUC)., Materials and Methods: Within a multi-institutional registry, 528 and 1,894 patients with VH BCa and pUC, respectively, were identified. The Weibull regression was used to detect the time points after which the risk of OCM exceeded the risk of recurrence during followup. The risk of OCM over time was stratified based on age and comorbidities, and the risk of recurrence on pathological stage and recurrence site., Results: Individuals with VH had a higher risk of recurrence (recurrence-free survival 30% vs 51% at 10 years, p <0.001) and shorter median time to recurrence (88 vs 123 months, p <0.01) relative to pUC. Among VH, micropapillary variant conferred the greatest risk of recurrence on the abdomen and lungs, and mixed variants carried the greatest risk of metastasizing to bones and other sites compared to pUC. Overall, surveillance should be continued for a longer time for individuals with VH BCa. Notably, patients younger than 60 years with VH and pT0/Ta/T1/N0 at radical cystectomy should continue oncologic surveillance after 10 years vs 6.5 years for pUC individuals., Conclusions: VH BCa is associated with greater recurrence risk than pUC. A followup scheme that is valid for pUC should not be applied to individuals with VH. Herein, we present a personalized approach for surveillance that may allow an improved shared decision.

Introduction: To compare surgical, oncologic, functional outcomes and complication rate between intracorporeal neobladder (ICNB) and extracorporeal neobladder (ECNB) orthotopic ileal neobladder of robot-assisted radical cystectomy (RARC) in patients with nonmetastatic bladder carcinoma (BC). Materials and Methods: From 2014 to 2019, we prospectively collected and retrospectively analyzed 101 patients with nonmetastatic BC treated with RARC and ortothopic neobladder. Chi-squared test estimated differences in proportions of functional and oncologic outcomes. Multivariable logistic regression models (MLRMs) focused on overall, early (<30 days from discharge), and late complication rate (>30 days from discharge) in ICNB vs ECNB. Results: Of all patients, 57 (56.4%) ICNB and 44 (43.6%) ECNB patients were identified. At least one complication occurred in 75.4% vs 72.7% in ICNB vs ECNB, respectively ( p  = 0.9). In MLRMs, focusing on complication rate, there was no statistically significant difference between ICNB vs ECNB for overall ( p  = 0.8), early ( p  = 0.6), and late complications ( p  = 0.8). No statistically significant differences were recorded for tumor relapse rate, cancer-specific and other cause mortality. No positive surgical margins were recorded in both groups. Daytime and nighttime continence recovery were 89.4% vs 87.1% ( p  = 1.0) and 63.8% vs 51.6% ( p  = 1.0) for ICNB vs ECNB. Potency recovery was 59.1% vs 54.3% ( p  = 0.5) for ICNB vs ECNB. Conclusions: No statistically significant differences in complication rate (overall, early, or late) were identified, when ICNB and ECNB were compared. Similarly, no statistically significant difference was found in oncologic and functional outcomes.

Purpose: To assess the impact of perioperative chemotherapy on survival in cN+ BCa patients and analyze it according to the pN status., Methods: A retrospective analysis was conducted on 639 BCa patients with cTanyN1-3M0 BCa treated with radical cystectomy (RC) and bilateral lymph node dissection (LND) with or without perioperative chemotherapy in ten tertiary referral centers from 1990 to 2017. Selected cN+ patients received induction chemotherapy (IC), whereas adjuvant chemotherapy (ACT) was delivered to selected pN+ patients. Univariable and multivariable Cox regression analyses were used to predict overall mortality (OM) after surgery, adjusting for clinicopathological confounders. Kaplan-Meier analyses assessed OM according to the treatment modality., Results: Overall, 356 (56%) patients were treated with surgery alone, 155 (24%) with IC followed by surgery, and 128 (20%) with ACT following surgery. Over a median follow-up of 25 months, 316 deaths were recorded. At univariable analysis, patients treated with IC and surgery had lower OM both considering cN+ [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.87, p = 0.004] and cN+pN- patients (HR 0.61, 95% CI 0.37-0.99, p = 0.05) compared to those treated with surgery alone. cN+pN+ patients treated with ACT experienced lower OM compared to those treated with IC or surgery alone at multivariable analysis (HR 0.40, 95% CI 0.22-0.74, p = 0.003)., Conclusion: Patients with cTany cN+ cM0 BCa benefit more in terms of OS when treated with IC followed by RC + LND compared to RC + LND alone, regardless of LNMs at final histopathology examination. More data are needed to assess the role of ACT in the management of cN+ patients.

Background: Bladder cancer is the ninth most common type of cancer worldwide. In the past, radical cystectomy via open surgery has been considered the gold-standard treatment for muscle invasive bladder cancer. However, in recent years there has been a progressive increase in the use of robot-assisted laparoscopic radical cystectomy. The aim of the current project is to investigate the surgical, oncological, and functional outcomes of patients with bladder cancer who undergo radical cystectomy comparing three different surgical techniques (robotic-assisted, laparoscopic, and open surgery). Pre-, peri- and post-operative factors will be examined, and participants will be followed for a period of up to 24 months to identify risks of mortality, oncological outcomes, hospital readmission, sexual performance, and continence., Methods: We describe a protocol for an observational, prospective, multicenter, cohort study to assess patients affected by bladder neoplasms undergoing radical cystectomy and urinary diversion. The Italian Radical Cystectomy Registry is an electronic registry to prospectively collect the data of patients undergoing radical cystectomy conducted with any technique (open, laparoscopic, robotic-assisted). Twenty-eight urology departments across Italy will provide data for the study, with the recruitment phase between 1st January 2017-31st October 2020. Information is collected from the patients at the moment of surgical intervention and during follow-up (3, 6, 12, and 24 months after radical cystectomy). Peri-operative variables include surgery time, type of urinary diversion, conversion to open surgery, bleeding, nerve sparing and lymphadenectomy. Follow-up data collection includes histological information (e.g., post-op staging, grading, and tumor histology), short- and long-term outcomes (e.g., mortality, post-op complications, hospital readmission, sexual potency, continence etc)., Discussion: The current protocol aims to contribute additional data to the field concerning the short- and long-term outcomes of three different radical cystectomy surgical techniques for patients with bladder cancer, including open, laparoscopic, and robot-assisted. This is a comparative-effectiveness trial that takes into account a complex range of factors and decision making by both physicians and patients that affect their choice of surgical technique., Trial Registration: ClinicalTrials.gov , NCT04228198 . Registered 14th January 2020- Retrospectively registered.

Introduction: Radical cystectomy (RC) is the gold standard treatment for patients with muscle-invasive or refractory non-muscle invasive bladder cancer. It is estimated that approximately 64% and 13% of RC patients experience any complication and major complications, respectively. Specialized immunonutrition (SIM) aims to reduce the rates of complications after RC. We reported surgical complication rates in RC patients who received (SIM group) versus who did not receive (no-SIM group) perioperative SIM. Moreover, we investigated factors associated with complications after RC., Material and Methods: This is a retrospective cohort study of 52 patients who underwent RC between April 2016 and December 2017. Overall, 26 (50%) patients received perioperative SIM. We recorded age, gender, Charlson Comorbidity Index (CCI), body mass index (BMI), Malnutrition Universal Screening Tool (MUST) score, unintentional weight loss (UWL), SIM drinks consume, surgical approach, urinary diversion, neoadjuvant chemotherapy (NAC), use of total parenteral nutrition (TPN), final pathology, length of stay (LOS), and complications., Results: SIM was associated with higher rates of documented infections ( P  = .03). Conversely, post-operative ileus was associated with higher rates of overall infections ( P  = .03). Median LOS was comparable within the 2 groups. Overall, 4 (15.38%) versus 0 (0%) patients in SIM versus no-SIM group were readmitted to hospital ( P  = .03). Age, CCI, NAC, and TPN were not associated with complication rates., Conclusions: SIM is not associated with lower rates of post-operative complications in RC candidates. Moreover, higher rates of documented infections were observed in the SIM group. Patients with post-operative ileus experienced more infections. Age, CCI, NAC, and TPN were not predictive of complications.

Objective: The objective of the study is to test the effect of age on cancer-specific mortality (CSM) in patients with urothelial carcinoma of the urinary bladder (UCUB), across all disease stages., Materials and Methods: Within the Surveillance, Epidemiology, and End Results (SEER) registry (2004-2016), we identified 207,714 patients. Age was categorized as: below 60 versus 60 to 69 versus 70 to 79 versus 80 years and above. Multivariable competing-risks regression (CRR) models were used according to disease stage (low-risk nonmuscle invasive: TaN0M0 low grade, high-risk nonmuscle invasive: Ta high grade or Tis-1N0M0, muscle invasive: T2-3N0M0, regional: T4N0M0/TanyN1-3M0, and metastatic: TanyNanyM1)., Results: Overall, 33,970 (16.4%) versus 52,173 (25.1%) versus 64,537 (31.1%) versus 57,034 (27.4%) patients were below 60 versus 60 to 69 versus 70 to 79 versus 80 years and above, respectively. In multivariable CRR models that focused on low-risk nonmuscle invasive UCUB, advanced age was associated with higher CSM rates (hazard ratio [HR]: 7.04 in patients aged 80 y and above, relative to below 60 y; P<0.001). Moreover, advanced age was also associated with higher CSM rates in high-risk nonmuscle invasive UCUB (HR: 2.77 in patients aged 80 y and above, relative to below 60 y; P<0.001) and in muscle invasive UCUB patients (HR: 1.38 in patients aged 80 y and above, relative to below 60 y; P<0.001). Conversely, lower CSM rates with advanced age were observed in multivariable CRR that focused on regional (HR: 0.91 for patients aged 80 y and above, relative to below 60 y; P=0.02) or metastatic UCUB (HR: 0.75 for patients aged 80 y and above, relative to below 60 y; P<0.001)., Conclusions: The direction and the magnitude of the association between advanced age and CSM in UCUB patients changes according to tumor stage. In low-risk nonmuscle invasive, high-risk nonmuscle invasive, and muscle invasive UCUB, more advanced age is associated with higher CSM rates. Conversely, in regional and metastatic UCUB patients, more advanced age is associated with lower CSM rates., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To test the effect of tumor location (urachal vs. non-urachal) on cancer-specific mortality (CSM) in patients with adenocarcinoma of the urinary bladder (ADKUB)., Materials and Methods: Within the Surveillance, Epidemiology, and End Results registry (2004-2016), we identified patients with non-metastatic (≤ T4N0M0) ADKUB. Stratification was made according to tumor location: urachal vs. non-urachal ADKUB. Kaplan-Meier plots and multivariable Cox regression models were fitted before and after 1:3 propensity score (PS) matching and separate Cox regression models were refitted before and after inverse probability of treatment weighting (IPTW)., Results: Of 1681 patients, 226 (13.5%) vs. 1455 (86.5%) harboured urachal vs. non-urachal ADKUB, respectively. Five-year cancer-specific survival (CSS) rates were, respectively, 75 vs. 67% for urachal vs. non-urachal ADKUB (p = 0.001). In subgroup analyses of ≤ T2N0M0 patients, 5-year CSS rates were, respectively, 84 vs. 73% for urachal vs. non-urachal ADKUB (p = 0.006). In subgroup analyses of T3-4N0M0 patients, 5-year CSS rates were, respectively, 68 vs. 49% for urachal vs. non-urachal ADKUB (p < 0.001). In multivariable Cox regression models, urachal ADKUB was associated with lower CSM rates (HR 0.6; p = 0.01). Virtually, the same findings were recorded after 1:3 PS matching (HR 0.6; p = 0.009) as well as when Cox regression models were refitted after IPTW (HR 0.7; p = 0.01)., Conclusion: The distinction between urachal vs. non-urachal ADKUB indicates better prognosis when the origin of the tumor is urachal, regardless of methodological approach used for the comparison.

Objectives: To test the effect of systemic chemotherapy on cancer-specific mortality (CSM) in patients with adenocarcinoma of the urinary bladder (ADKUB)., Materials and Methods: Within the Surveillance, Epidemiology, and End Results registry (2004 to 2016), we identified patients with localized (T2-3N0M0), regional (T4N0M0/TanyN1-3M0), and metastatic (TanyNanyM1) ADKUB. Temporal trends, Kaplan-Meier plots, and multivariable Cox regression models were used before and after 1:1 propensity score matching and inverse probability of treatment weighting., Results: Of 1537 patients with ADKUB, 834 (54.0%), 363 (23.5%), and 340 (22.5%) harbored localized, regional, and metastatic disease, respectively. The rates of chemotherapy use increased in localized (estimated annual percentage change [EAPC]: +2.7%; P=0.03) and regional ADKUB (EAPC: +2.4%; P=0.04). Conversely, chemotherapy rates remained stable in metastatic patients (EAPC: +1.6%; P=0.4). In multivariable Cox regression models, chemotherapy use was associated with lower CSM in metastatic ADKUB (hazard ratio [HR]: 0.5; P=0.003), but not in either localized (HR: 0.8; P=0.2) or in regional ADKUB (HR: 1.0; P=0.9). In metastatic ADKUB, the benefit of chemotherapy on CSM persisted after 1:1 propensity score matching (HR: 0.6; P=0.002) and after inverse probability of treatment weighting (HR: 0.4; P<0.001)., Conclusions: Chemotherapy improves survival in metastatic ADKUB. However, only one out of 2 such patients benefit from chemotherapy. In consequence, greater emphasis on chemotherapy use may be warranted in these patients. Conversely, no benefit was identified in localized or regional ADKUB.

Background: The objective of this study was to test the effect of chemotherapy and/or radical cystectomy (RC) and/or radiotherapy (RT) on survival of patients with non-metastatic small-cell carcinoma of the urinary bladder (SCCUB)., Materials and Methods: Within the Surveillance, Epidemiology, and End Results registry (2001-2016), we identified patients with non-metastatic (T1-4, N0, M0) SCCUB. Treatment was defined as: chemotherapy alone, chemotherapy + RC, and chemotherapy + RT. Temporal trends, cumulative incidence plots, and multivariable competing risks regression models were used., Results: Of 595 patients with SCCUB, 230 (38.5%), 159 (27%), and 206 (34.5%) were treated with chemotherapy alone, chemotherapy + RC, and chemotherapy + RT, respectively. The rates of chemotherapy + RC increased (estimated annual percentage changes [EAPC], +5.9%; P = .002). Conversely, chemotherapy alone (EAPC, -1.7%; P = .1) and chemotherapy + RT rates decreased (EAPC: -2.2%; P = .08). Overall, 5-year cancer-specific mortality (CSM) rates were 44%, 29%, and 40% for patients treated with chemotherapy alone, chemotherapy + RC, and chemotherapy + RT, respectively (P = .004). Relative to chemotherapy alone, patients treated with chemotherapy + RC experienced lower CSM (hazard ratio, 0.5; P < .001). Conversely, patients treated with chemotherapy + RT did not exhibit any CSM benefit (hazard ratio, 0.8; P = .2), when compared with chemotherapy alone., Conclusion: In contemporary patients with SCCUB with non-metastatic disease, the rates of chemotherapy + RC are increasing. Conversely, the rates of combined chemotherapy with RT and chemotherapy alone are decreasing. These patterns of treatment are in agreement with better cancer control in patients with SCCUB. In consequence, until more robust data become available, the combination of chemotherapy and RC should represent the recommended treatment strategy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: The aim of this multicenter study was to investigate the prognostic role of type 2 diabetes mellitus (T2DM) comorbidity in a large multi-institutional cohort of patients with primary T1HG/G3 non-muscle-invasive bladder cancer (NMIBC) treated with transurethral resection of the bladder (TURB)., Materials and Methods: A total of 1,172 patients with primary T1 HG/G3 who had NMIBC on re-TURB and who received adjuvant intravesical bacillus Calmette-Guérin therapy with maintenance were included. Endpoints were recurrence-free survival and progression-free survival., Results: A total of 231 (19.7%) of patients had T2DM prior to TURB. Five-year recurrence-free survival estimates were 12.5% in patients with T2DM compared to 36% in patients without T2DM, P < 0.0001. Five-year PFS estimates were 60.5% in patients with T2DM compared to 70.2% in patients without T2DM, P = 0.003. T2DM was independently associated with disease recurrence (hazard ratio = 1.41; 95% confidence interval = 1.20-1.66, P < 0.001) and progression (hazard ratio = 1.27; 95% confidence interval = 0.99-1.63, P < 0.001), after adjusting for other known predictive factors such as tumor size, multifocality, T1G3 on re-TURB, body mass index, lymphovascular invasion, and neutrophil-to-lymphocytes ratio., Conclusions: Given the potential implications for management, prospective validation of this finding along with translational studies designed to investigate the underlying biology of such an association are warranted., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: To analyze contemporary multimodality treatment rates, defined as radical cystectomy plus chemotherapy and/or radiotherapy, for pT2-3 any N-stage M0 non-urothelial carcinoma of urinary bladder patients. Additionally, we tested for the effect of multimodality treatment versus radical cystectomy alone on cancer-specific mortality., Methods: Within the Surveillance, Epidemiology and End Results database (2004-2015), 887 pT2-3 any N-stage M0 non-urothelial carcinoma of urinary bladder patients treated with radical cystectomy were identified. Kaplan-Meier plots, and univariable and multivariable Cox regression analyses focused on cancer-specific mortality rates., Results: Squamous cell carcinoma was recorded in 499 (56.3%) patients, neuroendocrine carcinoma in 246 (27.7%) and adenocarcinoma in 142 (16.0%). The highest proportion of multimodality treatment patients was recorded in neuroendocrine carcinoma (69.1%), relative to adenocarcinoma (34.5%) and squamous cell carcinoma (26.4%). A statistically significant annual increase was recorded in multimodality treatment rates in neuroendocrine carcinoma patients (46.7-74.2%, P < 0.01), but not in adenocarcinoma or squamous cell carcinoma patients. The 5-year cancer-specific mortality rate in neuroendocrine carcinoma patients was significantly lower after multimodality treatment versus radical cystectomy alone (37.0% vs 51.5%; P < 0.01), but no statistically significant differences were recorded in both adenocarcinoma (46.1% vs 35.5%; P = 0.8) and squamous cell carcinoma (41.4% vs 31.1%; P = 0.8) patients. In multivariable analyses, for neuroendocrine carcinoma patients, multimodality treatment was an independent predictor of a lower cancer-specific mortality rate (hazard ratio 0.58, P = 0.03)., Conclusions: Multimodality treatment has been increasingly used during the study period in neuroendocrine carcinoma patients, and it has translated into a cancer-specific mortality benefit. This is not the case for other non-urothelial carcinoma of urinary bladder patients, such as adenocarcinoma or squamous cell carcinoma., (© 2020 The Japanese Urological Association.)

Background: The present study tested cancer-specific (CSM) and overall mortality (OM) after partial cystectomy (PC) for variant histology bladder cancer (non-urothelial carcinoma of the urinary bladder UCUB), relative to UCUB and relative to radical cystectomy (RC)., Materials and Methods: Within the Surveillance, Epidemiology, and End Results registry (2001-2016), we identified patients with stage T1-T2N0M0 non-UCUB and UCUB who had undergone PC or RC. Non-UCUB included adenocarcinoma, squamous carcinoma, neuroendocrine carcinoma, and other histologic subtypes. First, CSM and OM after PC were compared between the non-UCUB and UCUB groups. Second, CSM and OM after PC were compared with RC in the non-UCUB group. Kaplan Meier plots and multivariable Cox regression models were used before and after inverse probability of treatment weighting., Results: Overall, 248 patients (16.3%) treated with PC had had non-UCUB. Of the 248 cases, 115 (46.5%), 50 (20%), 34 (14%), and 49 (19.5%) were adenocarcinoma, squamous carcinoma, neuroendocrine carcinoma, and other histologic subtypes, respectively. The comparison between PC in the non-UCUB and PC in the UCUB group showed higher CSM (hazard ratio, 1.4; P = .03) but the same OM rates (hazard ratio, 1.1; P = .7) in the non-UCUB group. The comparison between PC and RC for the non-UCUB group showed no CSM or OM differences., Conclusions: PC for non-UCUB was associated with higher CSM compared with PC for UCUB. However, PC instead of RC for select patients with non-UCUB appears not to undermine cancer-control outcomes. Thus, the excess CSM is probably unrelated to cystectomy type but could originate from differences in the tumor biology. These results could act as hypothesis generating for the design of future trials., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: We investigated the effect of partial cystectomy (PC) on cancer-specific mortality (CSM) and other-cause mortality (OCM) and the effect of pelvic lymph node dissection (PLND) during PC on CSM., Materials and Methods: Within the Surveillance, Epidemiology, and End Results database (2004-2015), 11,429 cases of nonmetastatic stage pT2-T3 urothelial carcinoma of the urinary bladder treated with either PC or radical cystectomy (RC) were identified. All comparisons between PC and RC relied on propensity score (PS; ratio, 1:1) adjusted univariable and multivariable logistic and competing risks regression models. In contrast, all comparisons between PLND and no PLND at PC relied on inverse probability of treatment weighting-adjusted univariable and multivariable Cox regression models., Results: Within the SEER database, PC had been performed in 979 patients (8.6%). The PC annual rates decreased from 11.0% to 6.8% during the study period (P < .001). In PS-adjusted multivariable analyses focusing on CSM and OCM, no statistically significant difference between the PC and RC groups (P = .2 and P = .3, respectively). The annual PLND rates with PC (50.3%) did not vary over time (P = .3). In the overall cohort and the PC subgroup, PLND was associated with a lower CSM rate (hazard ratio, 0.56; P < .001; and hazard ratio, 0.57; P < .001, respectively)., Conclusions: A small proportion of patients with stage pT2-T3 urothelial carcinoma of the urinary bladder were candidates for PC. In the PS-adjusted multivariable analyses, no statistically significant differences were found in CSM or OCM between the PC and RC groups. Within the PC group, PLND had been omitted 50% of the time despite its association with lower CSM., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The new severe acute respiratory syndrome virus (SARS-CoV-2) outbreak is a huge health, social and economic issue and has been declared a pandemic by the World Health Organization. Bladder cancer, on the contrary, is a well-known disease burdened by a high rate of affected patients and risk of recurrence, progression and death., Summary: The coronavirus disease (COVID-19 or 2019-nCoV) often involves mild clinical symptoms but in some cases, it can lead to pneumonia with acute respiratory distress syndrome and multiorgan dysfunction. Factors associated with developing a more severe disease are increased age, obesity, smoking and chronic underlying comorbidities (including diabetes mellitus). High-risk non-muscle-invasive bladder cancer (NMIBC) progression and worse prognosis are also characterized by a higher incidence in patients with risk factors similar to COVID-19. Immune system response and inflammation have been found as a common hallmark of both diseases. Most severe cases of COVID-19 and high-risk NMIBC patients at higher recurrence and progression risk are characterized by innate and adaptive immune activation followed by inflammation and cytokine/chemokine storm (interleukin [IL]-2, IL-6, IL-8). Alterations in neutrophils, lymphocytes and platelets accompany the systemic inflammatory response to cancer and infections. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for example have been recognized as factors related to poor prognosis for many solid tumors, including bladder cancer, and their role has been found important even for the prognosis of SARS-CoV-2 infection. Key Messages: All these mechanisms should be further analyzed in order to find new therapeutic agents and new strategies to block infection and cancer progression. Further than commonly used therapies, controlling cytokine production and inflammatory response is a promising field., (© 2020 S. Karger AG, Basel.)

Background: Basophils, eosinophils and monocytes may be involved in BCG-induced immune responses and be associated with outcomes of bladder cancer patients receiving intravesical BCG. Our objective was to explore the association of baseline counts of basophils, eosinophils and monocytes with outcomes of patients with high-grade T1 bladder cancer receiving a standard course of intravesical BCG., Methods: We retrospectively reviewed medical records of patients with primary T1 HG/G3 bladder cancer. After re-TURBT, patients were treated with a 6-week course of intravesical BCG induction followed by intravesical BCG every week for 3 weeks given at 3, 6, 12, 18, 24, 30 and 36 months from initiation of therapy The analysis of potential risk factors for recurrence, muscle invasion and cancer-specific and overall survival was performed using univariable Cox regression models. Those factors that presented, at univariate analysis, an association with the event at a liberal p < 0.1, have been selected for the development of a multivariable model., Results: A total of 1045 patients with primary T1 HG/G3 were included. A total of 678 (64.9%) recurrences, 303 (29.0%) progressions and 150 (14.3%) deaths were observed during follow-up. Multivariate analysis showed that logarithmic transformation of basophils count was associated with a 30% increment in the hazard of recurrence per unit increase of logarithmic basophils count (HR 1.30; 95% confidence interval 1.09-1.54; p = 0.0026). Basophil count modeled by quartiles was also significantly associated with time to recurrence [second vs. lower quartile HR 1.42 (1.12-1.79); p = 0.003, third vs. lower quartile HR 1.26 (1.01-1.57); p = 0.041; upper vs. lower quartile HR 1.36 (1.1-1.68); p = 0.005]. The limitations of a retrospective study are applicable., Conclusion: Baseline basophil count may predict recurrence in BCG-treated HG/G3 T1 bladder cancer patients. External validation is warranted.

Background: To test the effect of radical cystectomy (RC) with chemotherapy vs only chemotherapy on overall mortality (OM) in metastatic urothelial carcinoma of the urinary bladder (mUCUB)., Methods: Within the Surveillance, Epidemiology, and End Results registry (2004-2016), we identified patients with mUCUB. Stratification was made according to treatment: RC with chemotherapy vs only chemotherapy. Kaplan-Meier plots and multivariable Cox regression models were used before and after 1:1 propensity score (PS) matching and inverse probability of treatment weighting (IPTW)., Results: Of 2414 patients with mUCUB, 500 (21.0%) vs 1914 (79.0%) were treated with RC with chemotherapy vs only chemotherapy, respectively. In multivariable Cox regression models, RC with chemotherapy was associated with lower OM in the overall cohort (hazard ratio [HR], 0.5; P < .001), after 1:1 PS matching (HR, 0.5; P < .001), after IPTW (HR, 0.5; P < .001) and after accounting for number and location of metastases (HR, 0.5; P < .001). However, higher overall survival after RC with chemotherapy was only observed in patients with one metastatic site (21 vs 16 months; P = .001)., Conclusion: In contemporary patients with mUCUB, RC with chemotherapy is associated with lower OM rates, relative to chemotherapy alone, but only in patients with a single metastatic site. These individuals accounted for the vast majority of patients in whom an RC was performed, despite the presence of metastatic disease., (© 2019 Wiley Periodicals, Inc.)

Upper tract urinary carcinoma (UTUC) and bladder cancer (BCa) share similar biological, histological and pathological characteristics. These resemblances could explain the high rate of synchronous and metachronous tumors affecting both upper urinary tract and bladder. In patients affected by primary UTUC bladder recurrence is quite common and it represents one of the major concerns during the follow-up of patients who underwent radical nephroureterectomy. Conversely, UTUC recurrence after primary non-muscular invasive BCa is a relatively rare event. Moreover, there is no clear evidence on whether the use of Double-J stenting as drainage in patients affected by BCa increases the risk of UTUC recurrence. The aim of the current study was to summarize the most recent evidence regarding the bladder recurrence after UTUC surgical treatment, and the UTUC recurrence after stent positioning in patients affected by primary BCa.