Previous Bladder Cancer Research Articles

Advanced Age Impacts Survival After Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma

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. 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. 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). 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.

MP69-14 THE IMPLEMENTATION OF SYSTEMATIC BIOPSIES IN THE ENDOSCOPIC MANAGEMENT OF UPPER TRACT UROTHELIAL CANCER

You have accessJournal of UrologyCME1 Apr 2023MP69-14 THE IMPLEMENTATION OF SYSTEMATIC BIOPSIES IN THE ENDOSCOPIC MANAGEMENT OF UPPER TRACT UROTHELIAL CANCER Andrea Gallioli, Angelo Territo, Basile Giuseppe, Pietro Diana, Paolo Verri, Francesco Sanguedolce, Josep Maria Gaya, Pavel Gavrilov, Alessandro Uleri, Sofia Fontanet, Paula Izquierdo, Jordi Huguet, Ferran Algaba, Joan Palou, and Alberto Breda Andrea GallioliAndrea Gallioli More articles by this author , Angelo TerritoAngelo Territo More articles by this author , Basile GiuseppeBasile Giuseppe More articles by this author , Pietro DianaPietro Diana More articles by this author , Paolo VerriPaolo Verri More articles by this author , Francesco SanguedolceFrancesco Sanguedolce More articles by this author , Josep Maria GayaJosep Maria Gaya More articles by this author , Pavel GavrilovPavel Gavrilov More articles by this author , Alessandro UleriAlessandro Uleri More articles by this author , Sofia FontanetSofia Fontanet More articles by this author , Paula IzquierdoPaula Izquierdo More articles by this author , Jordi HuguetJordi Huguet More articles by this author , Ferran AlgabaFerran Algaba More articles by this author , Joan PalouJoan Palou More articles by this author , and Alberto BredaAlberto Breda More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003332.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Diagnosis of upper tract urothelial cancer (UTUC) is crucial. In this regard, uretheral systematic biopsies (USB) have never been considered. We aim to investigate the safety and usefulness of USB in the diagnosis of UTUC and its impact on disease management. METHODS: We relied on a prospectively maintained database of patients who underwent diagnostic ureteroscopy (URS) for UTUC between 2015-21. USB included at least 2 biopsies in each UT portion: pelvis, proximal, medium, and distal ureter. Perioperative complications were graded using the Clavien-Dindo (CD) classification. We assessed the surgical safety and diagnostic impact of USB and estimated the 2-yr nephroureterectomy free-survival (NFU-FS) according to USB results. Then, we investigated the added value of USB over high-risk tumor variables according to EAU prognostic model. Finally, uni and multivariable logistic regression (MLR) analyses investigated preoperative predictors of positive USB. RESULTS: Overall, 91/360 (25.3%) patients underwent USB. Compared to patients who did not undergo USB, USB did not increase the risk of perioperative and major (CD >3a) complications, nor the risk of readmission (all p>0.05). USB was positive in 43 (47.25%) cases, negative in 30 (33%) patients. 58/300 (19.3%) biopsies were not diagnostic. In 36 (39.5%) patients both USB and biopsy of a suspicious lesion were performed. In 7 (19.4%) cases, USB outperformed the biopsy of the lesion in detecting UTUC. 11 (12%) patients were diagnosed with a distal ureter tumor. In 5 (45.4%) cases USB detected UTUC in other upper tract portions. The 2-yr NFU-FS rates were 87.7% (95CI%: 78.1-98.5) vs 53% (95%CI: 39.4-71.2) (p=0.001) for negative vs positive USB patients. At Cox-regression model accounting for predefined variables, patients with positive USB (vs. negative) had a higher risk of being treated with NFU [Hazard ratio: 3.38, 95%CI: 1.46-7.80, p=0.004)]. At MLR analysis, after adjusting for age, pre-operative positive cytology, smoking status, previous bladder cancer and previous UTUC, patients with negative pre-operative CT scan had a higher probability of having a positive USB (Odds ratio: 8.36, 95%CI: 1.57-71.18, p=0.02). CONCLUSIONS: USB is a safe procedure and detected a non-visible tumor at URS in one over five patients. Positive USB increases the risk of radical treatment and possibly changes the treatment algorithm in almost 50% of the patients with distal ureteral tumor candidates to conservative management. When UTUC is suspected, patients with preoperative negative CT scan may benefit the most from USB. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e969 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Andrea Gallioli More articles by this author Angelo Territo More articles by this author Basile Giuseppe More articles by this author Pietro Diana More articles by this author Paolo Verri More articles by this author Francesco Sanguedolce More articles by this author Josep Maria Gaya More articles by this author Pavel Gavrilov More articles by this author Alessandro Uleri More articles by this author Sofia Fontanet More articles by this author Paula Izquierdo More articles by this author Jordi Huguet More articles by this author Ferran Algaba More articles by this author Joan Palou More articles by this author Alberto Breda More articles by this author Expand All Advertisement PDF downloadLoading ...

Ileal Conduit Necrosis Secondary to Spontaneous Retroperitoneal Hematoma

Case Presentation: A fifty-nine years old woman with previous muscle-invasive bladder cancer treated five years prior in another medical center with radical cystectomy and Bricker’s ureteroileostomy diversion, presented to the Emergency Room (ER) describing general discomfort, diarrhea, arterial hypotension and tachycardia. After conducting an imaging test, ileal conduit ischemia and mesenteric ischemia was diagnosed secondary to retroperitoneal hematoma. Ileal reservoir resection, resection of the ischemic intestine, and bilateral cutaneous ureterostomy were performed. Relevance: In patients with previous urinary diversion and acute abdominal pain, it is imperative to dismiss conduit involvement. Clinical Implications: In cases of acute abdomen with history of urinary diversion, physical examination and imaging tests can detect if the ileal reservoir has been compromised and, therefore, guide the adequate therapeutic approach. Conclusions: Identifying the complications of the urinary diversion in early stages in order to treat the underlying cause is advisable.

Clinical Determinants of Extraurinary Tract Recurrence and Survival after Radical Surgery for pT2 Upper Tract Urothelial Carcinoma

Oncologic outcomes for pT2N0M0 upper tract urothelial carcinoma (UTUC) after nephroureterectomy are not well defined, with most previous studies focused on a heterogeneous population. Therefore, we aimed to investigate the clinical determinants of extraurinary tract recurrence and survival after radical surgery in patients with localized UTUC. We retrospectively identified 476 patients with pT2N0M0 UTUC who underwent radical nephroureterectomy or ureterectomy between October 2002 and March 2022. To evaluate the prognostic impact, patients were divided into renal pelvic, ureteral, and both-region (renal pelvis plus synchronous ureter) groups based on tumor location. The outcomes included recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Associations were evaluated using multivariable Cox regression analyses for prognostic factors and Kaplan-Meier analyses for survival curves. The renal pelvic, ureteral, and both-region groups consisted of 151 (31.7%), 314 (66.0%), and 11 (2.3%) patients, respectively. Kaplan-Meier analyses comparing the three tumor types showed significant differences in 5-year RFS (83.6% vs. 73.6% vs. 52.5%, p = 0.013), CSS (88.6% vs. 80.7% vs. 51.0%, p = 0.011), and OS (83.4% vs. 70.1% vs. 45.6%, p = 0.002). Multivariable analyses showed that age >60 years, previous bladder cancer history, ureteral involvement (ureteral and both-regional groups), and positive surgical margins were significant negative prognostic factors for the studied outcomes. Patients with pT2 UTUC and presence of ureteral involvement had more frequent disease relapse. Subsequent adjuvant therapy regimens and close follow-up in patients with negative prognostic factors are warranted despite complete pathological removal of the tumor.

Assessment of association between lower ureteric excision technique and oncological outcomes for upper urinary tract urothelial carcinoma: retrospective analysis from the Scottish Renal Cancer Consortium

PurposeNephroureterectomy(NU) remains the gold-standard surgical option for the management of upper urinary tract urothelial carcinoma(UTUC). Controversy exists regarding the optimal excision technique of the lower ureter. We sought to compare post-UTUC bladder tumour recurrence across the Scottish Renal Cancer Consortium(SRCC).MethodsPatients who underwent NU for UTUC across the SRCC 2012–2019 were identified. The impact of lower-end surgical technique along with T-stage, N-stage, tumour location and focality, positive surgical margin, pre-NU ureteroscopy, upper-end technique and adjuvant mitomycin C administration were assessed by Kaplan–Meier and Cox-regression. The primary outcome was intra-vesical recurrence-free survival (B-RFS).ResultsIn 402 patients, the median follow-up was 29 months. The lower ureter was managed by open transvesical excision in 90 individuals, transurethral and laparoscopic dissection in 76, laparoscopic or open extra-vesical excision in 31 and 42 respectively, and transurethral dissection and pluck in 163. 114(28.4%) patients had a bladder recurrence during follow-up. There was no difference in B-RFS between lower-end techniques by Kaplan–Meier (p = 0.94). When all factors were taken into account by adjusted Cox-regression, preceding ureteroscopy (HR 2.65, p = 0.001), lower ureteric tumour location (HR 2.16, p = 0.02), previous bladder cancer (HR 1.75, p = 0.01) and male gender (HR 1.61, p = 0.03) were associated with B-RFS.ConclusionThese data suggest in appropriately selected patients, lower ureteric management technique does not affect B-RFS. Along with lower ureteric tumour location, male gender and previous bladder cancer, preceding ureteroscopy was associated with a higher recurrence rate following NU, and the indication for this should be carefully considered.

Uncovering additional predictors of urothelial carcinoma from voided urothelial cell clusters through a deep learning-based image preprocessing technique.

Urine cytology is commonly used as a screening test for high-grade urothelial carcinoma for patients with risk factors or hematuria and is an essential step in longitudinal monitoring of patients with previous bladder cancer history. However, the semisubjective nature of current reporting systems for urine cytology (e.g., The Paris System) can hamper reproducibility. For instance, the incorporation of urothelial cell clusters into the classification schema is still an item of debate and perplexity among expert cytopathologists because several previous works have disputed their diagnostic relevance. In this work, an automated preprocessing tool for urothelial cell cluster assessment was developed that divides urothelial cell clusters into meaningful components for downstream assessment (ie, population-based studies, workflow automation). In this work, an automated preprocessing tool for urothelial cell cluster assessment was developed that divides urothelial cell clusters into meaningful components for downstream assessment (ie, population-based studies, workflow automation). Results indicate that cell cluster atypia (i.e., defined by whether the cell cluster harbored multiple atypical cells, thresholded by a minimum number of cells), cell border overlap and smoothness, and total number of clusters are important markers of specimen atypia when considering assessment of urothelial cell clusters. Markers established through techniques to separate cell clusters may have wider applicability for the design and implementation of machine learning approaches for urine cytology assessment.

MP40-16 EXPRESSION ANALYSIS AND MUTATIONAL STATUS OF HISTONE METHYLTRANSFERASE KMT2D IN UPPER TRACT UROTHELIAL CARCINOMA

You have accessJournal of UrologyCME1 May 2022MP40-16 EXPRESSION ANALYSIS AND MUTATIONAL STATUS OF HISTONE METHYLTRANSFERASE KMT2D IN UPPER TRACT UROTHELIAL CARCINOMA Ekaterina Laukhtina, Ursula Lemberger, Andreas Bruchbacher, Dafina Ilijazi, David D’Andrea, Martin Susani, Dmitry Enikeev, Eva Compérat, Shahrokh F. Shariat, and Melanie R. Hassler Ekaterina LaukhtinaEkaterina Laukhtina More articles by this author , Ursula LembergerUrsula Lemberger More articles by this author , Andreas BruchbacherAndreas Bruchbacher More articles by this author , Dafina IlijaziDafina Ilijazi More articles by this author , David D’AndreaDavid D’Andrea More articles by this author , Martin SusaniMartin Susani More articles by this author , Dmitry EnikeevDmitry Enikeev More articles by this author , Eva CompératEva Compérat More articles by this author , Shahrokh F. ShariatShahrokh F. Shariat More articles by this author , and Melanie R. HasslerMelanie R. Hassler More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002600.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The gene coding for histone methyltransferase KMT2D is found among the top mutated genes in upper tract urothelial carcinoma (UTUC); however, there is a lack of data regarding its association with clinicopathologic features as well as survival outcomes. Therefore, we aimed to investigate KMT2D expression and mutation patterns and their utility as prognostic biomarkers in patients with UTUC. METHODS: A retrospective single-center study was conducted on tumor specimens from 51 patients treated with radical nephroureterectomy (RNU). Analysis of KMT2D expression on the protein level was performed by immunohistochemistry (IHC). Customized Next Generation Sequencing (NGS) was used to assess alterations in KMT2D exons. Cox-regression analyses were used to correlate KMT2D protein expression and mutational status with survival outcomes such as disease-free and overall survival. RESULTS: KMT2D expression was increased in patients with a previous history of bladder cancer (25% vs. 0%, p=0.02). NGS analysis of KMT2D exons in 27 UTUC tumors revealed a significant association between pathogenic KMT2D variants and tumor location (p=0.02). Pathogenic KMT2D variants were predominantly found in patients with non-pelvic or multifocal tumors (60% vs. 14%), while the majority of patients with pelvic tumor location (81% vs. 20%) did not harbor pathogenic KMT2D alterations. Both IHC and NGS analyses of KMT2D failed to detect a statistically significant association between KMT2D protein or KMT2D gene alteration status and clinical variables such as stage/grade of the disease as well as survival outcomes (all p >0.05). CONCLUSIONS: In this study, KMT2D protein expression and KMT2D mutational status did not emerge as prognostic markers for UTUC. However, KMT2D alterations and protein expression were associated with features of biologically aggressive UTUC such as multifocality, ureteral location, and previous bladder cancer. Therefore, KMT2D seems to hold the potential of improving our clinical decision in UTUC regarding perioperative systemic therapy and/or additional intravesical therapy. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e681 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ekaterina Laukhtina More articles by this author Ursula Lemberger More articles by this author Andreas Bruchbacher More articles by this author Dafina Ilijazi More articles by this author David D’Andrea More articles by this author Martin Susani More articles by this author Dmitry Enikeev More articles by this author Eva Compérat More articles by this author Shahrokh F. Shariat More articles by this author Melanie R. Hassler More articles by this author Expand All Advertisement PDF DownloadLoading ...

A Comparative Study of the Triglycerides/HDL Ratio and Pseudocholinesterase Levels in Patients with Bladder Cancer.

Background: Lipid alterations may serve as potential tumour biomarkers. The ratio of triglycerides to HDL cholesterol (TG/HDL ratio) is associated with various cancers. Pseudocholinesterase (PChE) activity, involved in TG hydrolysis, plays an important role in the metabolism of lipoprotein. There is scarce data assessing the reliability of both the TG/HDL ratio and PChE levels in correctly classifying patients suffering from bladder cancer. Methods: Three hundred and ninety-six patients undergoing cystoscopy or transurethral resection of the bladder (TURB), broken into two major groups, i.e., patients with histologically confirmed, non-metastatic bladder cancer (n = 208) and without bladder cancer (no bladder cancer, n = 188), formed the study population. The last group was split into two subgroups consisting of a cohort of patients never suffering from bladder cancer but with other bladder diseases (no CaBD, n = 100) and another cohort formed by patients characterised by eradicated bladder cancer after TURB with no recurrence during a three-month follow-up (previous bladder cancer, n = 88). Pieces of information by both metabolic derangement (the presence of type 2 diabetes mellitus), hypertension and lipid profile were retrieved from patient records upon entry to the study. Sensitivity, specificity, areas under the ROC (AUROC) of the TG/HDL ratio, and PChE levels were used in diagnostic decision making. Results: The TG/HDL ratio as well as PChE concentrations of bladder cancer patients were significantly different when compared to those with previous bladder cancer and the no CaBD patients (p = 0.023 and 0.0004, respectively). There was an independent role of both the TG/HDL ratio and PChE levels in predicting the presence of bladder cancer (OR: 1.22 and 0.99, respectively), but the reliability of the TG/HDL ratio (AUROC: 0.587) was superior to that of PChE levels (AUROC: 0.374). The AUROC of a new parameter resulting from the combination of the TG/HDL ratio with PChE levels showed a further increment in the discriminant power of the bladder cancer presence (0.6298), interestingly with a negative predictive value (89%) according to the Bayesian approach. The cut-off of the TG/HDL ratio, the main marker of the present study that better distinguishes bladder cancer from no bladder cancer patients, was 2.147. Discussion and Conclusions: The reliability of the TG/HDL ratio is based on the fact that this parameter likely mirrors the insulin resistance (IR) underlying bladder cancer patients. Furthermore, PChE levels evidence both IR and the associated non-alcoholic fatty liver disease. The TG/HDL ratio and PChE levels as well as their combined use could help physicians to assess/confirm the presence of this very common cancer, where early detection is important to ensure the best therapeutical approach.

Effect of prior radiation on stage, differentiation, and survival in bladder cancer.

Clinically significant differences in radiation-related bladder tumors are not well-characterized, and survival analyses are needed. In this study, we aimed to utilize a national cancer database to evaluate the effect of prior radiation on tumor characteristics and survival in bladder cancer patients. The Surveillance, Epidemiology, and End Results (SEER) 9 database was queried to identify patients diagnosed with bladder cancer as a second malignancy. Patients having undergone radiation prior to developing bladder cancer were selected for comparative analysis. Logistic regression was used to generate odds ratios to evaluate differences in differentiation, stage, grade, and tumor size. Kaplan-Meier analysis and Cox non-proportional hazards regression models were used to assess the association between previous radiation and bladder cancer survival. A total of 25,408 patients were identified, of which 14,570 patients had sufficient data for analysis. Of these, 5968 (41.0%) received radiation for their primary malignancy. Prior radiation conferred a lower risk of developing moderately- or poorly-differentiated bladder tumors and muscleinvasive or node-positive disease. An increased risk of squamous cell carcinoma was noted (OR 1.43, CI 1.06-1.93). Prior radiation led to an increased risk of bladder cancer-specific (HR 1.13, CI 1.03-1.24) mortality at 5years. The greatest effect of prior radiation was an increased risk of bladder cancer-specific mortality for carcinoma in situ at 5years (OR 2.37, CI 1.45-3.86). Prior radiation is associated with lower grade and stage of bladder tumors in addition to worse cancer-specific survival.

Impact of previous, simultaneous or intravesical recurrence bladder cancer on prognosis of upper tract urothelial carcinoma after nephroureterectomy: a large population-based study.

BackgroundCurrently, the impact of previous, simultaneous, or subsequent bladder cancer on the prognosis of upper urinary tract urothelial carcinoma (UTUC) is controversial. We aimed to investigate the impact of previous, simultaneous or intravesical recurrence (IVR) bladder cancer on the prognosis of UTUC based on a large population-based cohort from the Surveillance, Epidemiology, and End Results (SEER) database.MethodsA total of 8,431 UTUC patients diagnosed from 2004 to 2018 met the inclusion criteria were identified based on the SEER database. We evaluated the impact of bladder cancer on the prognosis of UTUC by Kaplan-Meier method and propensity score matching (PSM).ResultsIn all, 6,831 patients only had UTUC (UTUC-only), 880 patients with previous or simultaneous bladder cancer (UTUC-Bca), 720 patients with IVR (UTUC-IVR). After adjusting baseline covariates that varied significantly among groups, we found UTUC-Bca cohort, regardless of tumor grade and stage, had poorer prognosis than UTUC-only cohort. In general, we demonstrated IVR had no significant impact on the prognosis of UTUC compared to PSM matched patients without IVR. However, subgroup analysis revealed that UTUC patients with subsequent MIBC recurrence or shorter interval (<20 months) between UTUC and IVR had worse prognosis compared with UTUC-only cohort.ConclusionsUTUC patients with previous or simultaneous bladder cancer, IVR with MIBC, and shorter interval between UTUC and IVR were significant predictor for worse prognosis. Thus, more stringent postoperative surveillance and active treatment strategies should be considered for UTUC patients with those risk factors.

Risk Factors Leading to Radical Cystectomy in Patients Who Had Undergone Nephroureterectomy

Purpose: To identify the risk factors leading to radical cystectomy in patients who had undergone nephroureterectomy (NUx).Materials and Methods: We retrospectively reviewed the medical records of patients with upper tract urothelial carcinoma who underwent NUx during 2011–2019 and excluded patients with metastatic cancer. In total 646 patients were included in this study; of these, 532 had no previous bladder cancer history. Follow-up was performed every 3 months for 2 years after NUx was administered, and recurrence was confirmed using cystoscopy, urine cytology, computed tomography, and chest radiography. Bladder recurrence was confirmed through biopsy, urine cytology, or radiologic examination. Univariate and multivariate Cox regression analyzes were performed for statistical analysis of risk factors leading to radical cystectomy in patients undergoing NUx.Results: Lymphovascular invasion (LVI) (hazard ratio [HR], 4.728; 95% confidence interval [CI], 1.463–15.570; p=0.011), previous transurethral resection of bladder tumor history (HR, 3.825; 95% CI, 1.164–12.571; p=0.027), and intravesical recurrence (IVR) within 6 months (HR, 3.733; 95% CI, 1.091–12.778; p=0.036) in patients undergoing NUx are predictors of radical cystectomy implementation. In a multivariate analysis of patients without bladder cancer history, bladder recurrence was identified as a predictor of radical cystectomy implementation, if it occurred within 6 months of NUx (HR, 8.608; 95% CI, 1.545–47.976; p=0.014).Conclusions: LVI and IVR within 6 months and previous bladder cancer history are factors that can predict the need for radical cystectomy after NUx. Even in patients without bladder cancer history, early bladder recurrence within 6 months is a major predictor of radical cystectomy.

Expression Analysis and Mutational Status of Histone Methyltransferase KMT2D at Different Upper Tract Urothelial Carcinoma Locations.

The gene coding for histone methyltransferase KMT2D is found among the top mutated genes in upper tract urothelial carcinoma (UTUC); however, there is a lack of data regarding its association with clinicopathologic features as well as survival outcomes. Therefore, we aimed to investigate KMT2D expression, mutation patterns, and their utility as prognostic biomarkers in patients with UTUC. A single-center study was conducted on tumor specimens from 51 patients treated with radical nephroureterectomy (RNU). Analysis of KMT2D protein expression was performed using immunohistochemistry (IHC). Customized next-generation sequencing (NGS) was used to assess alterations in KMT2D exons. Cox regression was used to assess the relationship of KMT2D protein expression and mutational status with survival outcomes. KMT2D expression was increased in patients with a previous history of bladder cancer (25% vs. 0%, p = 0.02). The NGS analysis of KMT2D exons in 27 UTUC tumors revealed a significant association between pathogenic KMT2D variants and tumor location (p = 0.02). Pathogenic KMT2D variants were predominantly found in patients with non-pelvic or multifocal tumors (60% vs. 14%), while the majority of patients with a pelvic tumor location (81% vs. 20%) did not harbor pathogenic KMT2D alterations. Both IHC and NGS analyses of KMT2D failed to detect a statistically significant association between KMT2D protein or KMT2D gene alteration status and clinical variables such as stage/grade of the disease or survival outcomes (all p > 0.05). KMT2D alterations and protein expression were associated with UTUC features such as multifocality, ureteral location, and previous bladder cancer. While KMT2D protein expression and KMT2D mutational status do not seem to have prognostic value in UTUC, they appear to add information to improve clinical decision-making regarding the type of therapy.

742 Transurethral LASER Ablation (TULA): A Safe and Well Tolerated Procedure for The Treatment of Bladder Tumours Up To 4cm In Diameter in An Outpatient Setting

Abstract Aim Traditionally the management of recurrent non-muscle invasive bladder cancer (NMIBC) involves rigid cystoscopy and bladder biopsies/tumour resection under general/regional anaesthesia. As a result, many frail patients endure frequent anaesthetics and therefore are at increased risk of adverse outcomes including cognitive decline. Discontinuation of anti-platelet/anti-coagulation is not required for TULA. An outpatient TULA service was recently started at our trust. We present a case series of our first 4 months data. Method All TULA cases (n = 39) performed between Aug-Dec 2020 were included. Data was gathered prospectively including patient demographics, co-morbidities, initial cancer diagnosis and number of subsequent recurrences, post-procedural complications, and patient procedural satisfaction. Results Median age was 82 years (range 34-96) and median number of co-morbidities were 4 (range 0-10). Previous bladder cancer diagnosis was present for 85% with the most common initial stage G2pTa (n = 11). Median number of recurrences was 1 (range 1-5). Median patient perceived pain score was 3 (range 1-7) with 100% of patients preferring TULA over TURBT. Reasons included reduced procedural time (n = 18) and enhanced recovery (n = 15). Only 1 patient was readmitted post-procedure due to haematuria, however urine was clear after catheterisation and the patient was discharged. Conclusions TULA is safe for all low risk NMIBC, particularly for frail patients. It is well tolerated and facilitates improved patient experience. It also alleviates demand on theatre capacity and inpatient beds which has a positive effect on surgical waiting lists. Further audit of clinical outcomes should continue as recommended by NICE.

The Risk of Bladder Cancer in Type 2 Diabetes Mellitus with Combination Therapy of SGLT-2 Inhibitors and Pioglitazone.

Background: Either sodium-glucose cotransporter-2 (SGLT-2) inhibitors or pioglitazone (Pio) has doubtful issues of bladder cancer, especially for the combination therapy with these two drugs. Our study aimed to investigate the risk of bladder cancer under combination therapy of SGLT-2 inhibitors and Pio. Materials and Methods: We included 97,024 patients with type 2 diabetes mellitus (T2DM) in the Chang Gung Research Database in Taiwan from 1 January 2016 to 31 December 2019. The primary outcome was newly diagnosed bladder cancer after combination therapy with SGLT-2 inhibitors and Pio. Group 1 received both study drugs, group 2 received SGLT-2 inhibitors, group 3 received Pio, and group 4 received non-study drugs (the reference group). The secondary outcome in each group was all-cause mortality. Results: In group 1, no newly diagnosed bladder cancer was detected after a mean 2.8-year follow-up and all-cause mortality decreased significantly (adjusted hazard ratio (AHR), 0.70; 95% confidence interval (CI), 0.54–0.92) in comparison to the reference group (group 4). In group 2 and group 3, no trend of increased bladder cancer was observed (group 2: AHR 0.49, 95% CI 0.05–4.94; group 3: AHR 0.48, 95% CI 0.15–1.58) and it still reduced all-cause mortality (group 2: AHR 0.83, 95% CI 0.70–0.99; group 3: AHR 0.90, 95% CI 0.83–0.99). Conclusions: In T2DM patients without previous or active bladder cancer, the combination therapy of SGLT-2 inhibitors and Pio was not associated with newly diagnosed bladder cancer and had lower all-cause mortality.

Prognostic significance of tumor multifocality on outcomes in patients with upper tract urothelial carcinoma after radical nephroureterectomy: A cohort study

To identify the prognostic impact of tumor multifocality on upper tract urothelial carcinoma (UTUC) outcomes in patients treated with radical nephroureterectomy (RNU). Study included 342 consecutive patients with UTUC. Tumor multifocality was defined as the synchronous presence of 2 or more pathologically confirmed tumors in any upper urinary tract location. Cox regression analyses were used to address recurrence-free (RFS) and cancer-specific survival (CSS) estimates. Tumor multifocality was significantly associated with a history of previous non-muscle invasive bladder cancer (P < 0.001), tumor size (P < 0.001), gender (P = 0.009), tumor location (P = 0.005), and anemia (P = 0.01). The Kaplan–Meier method showed that tumor multifocality was significantly associated with worse recurrence-free survival (P < 0.001, log rank). Using multivariate analysis, tumor multifocality (HR, 2.86; 95% CI, 2.06 – 3.99; P < 0.001) was independently associated with recurrence free survival. During the follow-up, a total of 128 (37.4%) patients died, including 92 (28.2%) from UTUC. However, tumor multifocality was not associated with CSS (HR, 1.29; 95% CI, 0.89 – 1.96; P = 0.21) in univariate Cox regression analyses. Tumor stage (HR, 11.1; 95% CI, 3.64 – 33.8; P < 0.001), lymph node status (HR, 2.04, 95% CI, 1.05 – 3.94; P = 0.03) and preoperative anemia (HR, 3.50, 95% CI, 2.02 – 6.08; P < 0.001) were the only independent predictors associated with worse cancer-specific survival. Tumor multifocality is an independent prognostic factor of disease recurrence in patients treated with RNU for UTUC. Tumor multifocality is unable to predict cancer specific survival in a single-center series of consecutive patients who were treated with RNU.

Comparative analysis of patients with upper urinary tract urothelial carcinoma in black-foot disease endemic and non-endemic area

BackgroundA high incidence of upper urinary tract urothelial carcinoma has been reported in the southwestern area of Taiwan, where arsenic water contamination was considered the main cause. However, there is no definite proof to show a correlation between arsenic water contamination and upper urinary tract urothelial carcinoma. To investigate the clinical and epidemiological features of patients with upper urinary tract urothelial carcinoma between arsenic water endemic and non-endemic areas, we analyzed patients in terms of characteristics, stratified overall survival, disease-free survival, and cancer-specific survival.MethodsThe records of a total of 1194 patients diagnosed with upper urinary tract urothelial carcinoma were retrospectively reviewed. Clinical data and current medical status were collected from the medical records. Statistical analyses were performed to determine the clinical variables and stratified survival curves between endemic and non-endemic groups.ResultsFemale predominance was revealed in both endemic and non-endemic groups (male:female ratio = 1:1.2–1.4). No statistical differences were found in histological types, staging, and tumor size between the two groups. Nonetheless, patients with characteristics of aging and having end-stage renal disease were outnumbered in the non-endemic group, while a higher prevalence of previous bladder tumors and more ureteral tumors were found in the endemic group. Adjusted stratified cumulative survival curves suggested a poorer prognosis in endemic patients, especially in disease-free survival of early stage disease.ConclusionsA higher mortality rate with more previous bladder cancer history and ureteral tumors was seen in patients with upper urinary tract urothelial carcinoma residing in the arsenic water contamination area. This may be attributed to the long-term carcinogenic effect of arsenic underground water.

Significance of the timing of ureteral ligation on prognosis during radical nephroureterectomy for upper urinary tract urothelial cancer.

To investigate the impact on intravesical recurrence and prognosis according to the ureteral ligation timing during radical nephroureterectomy for upper urinary tract urothelial carcinoma. We carried out a retrospective chart review of 664 patients with non-metastatic upper urinary tract urothelial carcinoma who underwent radical nephroureterectomy with ureteral ligation (supplementary analysis of JCOG1110A). We excluded patients with previous and/or synchronous bladder cancer, clinically node-positive disease, no ureteral ligation data, those without ureteral ligation and those with any missing data. We investigated the cumulative incidence of intravesical recurrence and cancer-specific mortality, and overall survival between patients with ureteral ligation before renovascular ligation (early ureteral ligation), or ureteral ligation after renovascular ligation (late ureteral ligation). Early and late ureteral ligation was carried out in 243 patients (36.6%) and 421 patients (63.4%), respectively. Intravesical recurrence occurred in 218 patients (32.8%) during follow up (median 3.9years). No significant difference in the intravesical recurrence was found between early and late ureteral ligation groups. Meanwhile, survival in the early ureteral ligation group was significantly worse compared with the late ureteral ligation group. Multivariable analysis showed that early ureteral ligation was an independent prognostic factor for overall survival (hazard ratio 1.88, 95% confidence interval 1.24-2.85, P=0.003) and cancer-specific mortality (hazard ratio 1.93, 95% confidence interval 1.14-3.25, P=0.014). Our findings suggest that the incidence of intravesical recurrence is not affected by the timing of ureteral ligation during radical nephroureterectomy. However, early ureteral ligation might have a negative impact on survival outcomes.

Does Xylinas' nomogram accurately predict intravesical recurrence risk after radical nephroureterectomy for primary upper urinary tract urothelial carcinoma when applied to Asian populations?

To validate a prognostic nomogram (Xylinas' nomogram) for intravesical recurrence after radical nephroureterectomy for primary upper urinary tract urothelial carcinoma patients of Asian descent. Clinicopathological and survival data from 243 primary urinary tract urothelial carcinoma patients who underwent radical nephroureterectomy with bladder cuff excision between January 2004 and May 2017 were collated. Univariate and multivariable Cox regression analyses were performed to identify independent risk factors associated with intravesical recurrence-free survival. External validation was determined using regression coefficients abstracted from previously published data. Performance was then quantified through calibration and discrimination, according to concordance indexes (c-index) in receiver operating characteristic curves. 163 patients met our eligibility criteria and were finally included in this study. At a median follow-up of 60months, intravesical recurrence occurred in 29.4% (n=48). Multivariable analysis revealed that being male, ureteral tumor location, tumor multifocality and previous bladder cancer were independent prognostic factors of intravesical recurrence-free survival. When Xylinas' nomogram was applied to our cohort, the discriminatory power was found to be roughly equivalent with a c-index of 68.3% for the reduced model and 68.4% for the full model. Calibration plots also revealed intravesical recurrence predictions at 3, 6, 12, 18, 24 and 36months had relative concordance. Contrasting the respective performances of the reduced and full model suggests there is no significant difference between the two (all P>0.05). This nomogram appears accurate at predicting intravesical recurrence after radical nephroureterectomy for primary urinary tract urothelial carcinoma in Asian populations. However, it remains necessary to data mine for unknown prognostic factors for optimization. Further external validation is required across larger, ethically diverse populations before applying this nomogram in clinical practice.

DaBlaCa-11: Photodynamic Diagnosis in Flexible Cystoscopy—A Randomized Study With Focus on Recurrence

ObjectiveTo examine whether photodynamic diagnosis (PDD) in addition to flexible cystoscopy in the outpatient clinic can reduce risk of tumor recurrence in patients with previous nonmuscle invasive bladder cancer. PDD is an optical technique that enhances the visibility of pathologic tissue and helps guidance tumor resection. MethodsFrom February 2016 to December 2017, 699 patients from 3 urologic departments in Denmark were enrolled in a randomized controlled trial. Four months after transurethral resection of bladder tumor patients were randomized 1:1 to either an intervention group (hexaminolevulinate was instilled in the bladder before flexible cystoscopy with PDD video cystoscope) or a control group (white light flexible cystoscope), only. Primary endpoint was tumor recurrence within 8 months from the randomization. Secondary outcomes were numbers of procedures in general anesthesia, time to the first recurrence, differences in tumor size, risk of tumor progression, and identification of carcinoma in situ. ResultsA total of 351 patients were allocated to the intervention group (flexible PDD), and 348 to the control group (flexible white light). Throughout the following 8 months after randomization, only 117 patients in the intervention group had at least 1 tumor recurrence compared to 143 patients in the control group (P = .049). Odds ratio of 0.67 (P = .02, 95% CI: 0.48-0.95) correlates with a tumor reduction of 33% in favor of the intervention group. ConclusionUse of PDD in a routine surveillance cystoscopy first time after transurethral resection of bladder tumor for nonmuscle invasive bladder cancer reduces subsequent risk of tumor recurrence compared to WL cystoscopy alone.

Case Report: A rare case of BCGitis in a patient with bladder cancer treated with the BCG vaccine

The Bacillus Calmette Guérin (BCG) vaccine was initially produced as a vaccine against tuberculosis. BCG is an attenuated live strain of Mycobacterium bovis and has been widely used as an immunotherapy over the last years in bladder cancer. We describe a case of a 61-year-old Caucasian male with previous bladder cancer, who had been treated for the last 15 months with instillation of BCG, admitted with 3-week evolution history of fever (38ºC), asthenia, anorexia and a weight loss of 6kg. The patient’s condition deteriorated leading to sepsis. A liver biopsy was performed showing granulomatous dispersed through all the parenchyma. Empirical therapy for M. bovis was started with good response. Even though it is rare, BCGitis must be ruled out in any patient submitted to immunotherapy with BCG and prompt therapy started if disseminated disease is present, which improves the outcome.