Surveillance Of Bladder Cancer Research Articles

Deregulated molecular genetic pathways in urinary bladder cancer with the importance of molecular biomarkers in diagnosis and follow-up- A comprehensive and updated review

This article reviews and compares various currently available non-invasive, molecular biomarker-based tests for bladder cancer (BC) detection, and evaluates other potential molecules that may be used for BC diagnosis and surveillance. Currently, urinary cytology and periodic cystoscopies are clinically recommended for the diagnosis and monitoring of BC. Though highly specific, urinary cytology lacks sensitivity, whereas cystoscopies are invasive tests that are uncomfortable for the patient. Molecular biomarkers associated with BC progression form the basis for various available non-invasive tests. Urinary proteins like NMP22, MCM5 and Human complement factor-H related protein (BTA) are detected by ELISA/Immunochromatographic assay devices (NMP22, BTA, ADXBLADDER). Chromosomal abnormalities reported in BC -aneuploidy in chromosomes 3, 7, and 17 and deletions in chromosome 9- are detected by the Fluorescence in situ Hybridization based UroVysion test. Tumor antigens like sulfated mucin glycoproteins and glycosylated CEA help to light up urothelial carcinoma cells exfoliated into urine (uCyt+). Mutations in TERTp, FGFR3, KRAS, HRAS, TP53, CDKN2A, ERBB2 and PIK3CA contribute to BC progression and these are detected in tumor DNA by RT-qPCR, NGS and/or Sanger sequencing-based assays (Uromonitor, UroSEEK, AssureMDX). mRNA levels of genomic markers frequently deregulated in BC like IGFBP5, HOXA13, MDK, CDC2, CXCR5, IGF2, ABL1, CRH, UPK1B and ANXA10 are assesed by CxBladder and Xpert Bladder Cancer Monitor. BC associated changes in DNA methylation are detected by real time PCR and NGS based assays (EpiCheck, UroMark, AssureMDX). These tests have not yet been formally indicted into clinical practice but can serve as sensitive indicators for early diagnosis, disease monitoring, and treatment response in BC. Keywords: bladder cancer, biomarkers, non-invasive tests, molecular events in bladder cancer, genetic changes in bladder cancer

MP51-04 THE EXSTROPHY EXPERIENCE: A NATIONAL SURVEY ASSESSING URINARY CONTINENCE, BLADDER MANAGEMENT, AND ONCOLOGIC OUTCOMES IN ADULTS

You have accessJournal of UrologyPediatric Urology IV (MP51)1 Sep 2021MP51-04 THE EXSTROPHY EXPERIENCE: A NATIONAL SURVEY ASSESSING URINARY CONTINENCE, BLADDER MANAGEMENT, AND ONCOLOGIC OUTCOMES IN ADULTS Natalia Arias Villela, Kelly Harris, Ridwan Alam, Wayland Wu, Rachel Davis, Pamela Artigas, Heather Di Carlo, and John Gearhart Natalia Arias VillelaNatalia Arias Villela More articles by this author , Kelly HarrisKelly Harris More articles by this author , Ridwan AlamRidwan Alam More articles by this author , Wayland WuWayland Wu More articles by this author , Rachel DavisRachel Davis More articles by this author , Pamela ArtigasPamela Artigas More articles by this author , Heather Di CarloHeather Di Carlo More articles by this author , and John GearhartJohn Gearhart More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002077.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The bladder exstrophy-epispadias complex (BEEC) is a rare spectrum of congenital genitourinary malformations with an incidence of 1:10,000 to 1:50,000. Advances in reconstructive surgical techniques have improved clinical outcomes, but there is a paucity in data about disease sequela in adulthood. This is the largest survey to date in the United States exploring the urinary continence, bladder management, and oncologic outcomes in adults with BEEC. METHODS: Respondents were over the age of 18 with a diagnosis of bladder exstrophy, cloacal exstrophy, or epispadias. They were treated at the authors’ institution, included in the Association for the Bladder Exstrophy Community (ABeC) mailing list, and/or engaged in ABeC social media. A survey was created using uniquely designed questions and validated questionnaires. Survey responses between May 2020 and July 2020 were processed using Research Electronic Data Capture. Quantitative and qualitative statistics were used to analyze the data with significance at p<0.05. RESULTS: A total of 159 patients completed the survey. The median age was 31.5 years (IQR 25.9-45.9). Most patients (>70%) considered themselves continent of urine, with a median satisfaction score of 74 (IQR 50-97) on a scale from 0 to 100. There was less leakage among those with a continent urinary diversion compared to those who void or catheterize per urethra (p=0.003). Patients with intestinal-urinary tract reconstruction, such as augmentation cystoplasty or neobladder creation, were more likely to perform bladder irrigations (p=0.03). There was no difference in urinary tract infection (UTI) (p=0.497) or recurrent UTIs (p=0.117) among patients with and without intestinal-urinary tract reconstruction. Three (1.9%) patients were diagnosed with bladder cancer. A small portion of patients (27.2%) were given bladder cancer surveillance recommendations by a physician. CONCLUSIONS: Most patients achieved a satisfactory level of urinary continence, with the best outcomes in those with a continent urinary diversion. Those with intestinal-urinary tract reconstruction were more likely to perform bladder irrigations, perhaps to avoid complications from intestinal mucous production. The rates of UTI and recurrent UTIs were not affected by the type of genitourinary reconstruction. Bladder cancer rate was low although long-term follow-up is needed. Periodic monitoring of the upper urinary tract and bladder cancer surveillance is likely beneficial in this patient population. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e897-e897 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Natalia Arias Villela More articles by this author Kelly Harris More articles by this author Ridwan Alam More articles by this author Wayland Wu More articles by this author Rachel Davis More articles by this author Pamela Artigas More articles by this author Heather Di Carlo More articles by this author John Gearhart More articles by this author Expand All Advertisement Loading ...

PD63-03 UTILITY OF BLUE LIGHT FLEXIBLE CYSTOSCOPY FOR BLADDER CANCER SURVEILLANCE AFTER INTRAVESICAL THERAPY

You have accessJournal of UrologyBladder Cancer: Non-invasive III (PD63)1 Sep 2021PD63-03 UTILITY OF BLUE LIGHT FLEXIBLE CYSTOSCOPY FOR BLADDER CANCER SURVEILLANCE AFTER INTRAVESICAL THERAPY Sanam Ladi Seyedian, Xiaosong Meng, Sidney Roberts, Hamed Ahmadi, Jeffrey Howard, Iftach Chaplin, Aditya Bagrodia, Vitaly Margulis, Solomon Woldu, Yair Lotan, and Siamak Daneshmand Sanam Ladi SeyedianSanam Ladi Seyedian More articles by this author , Xiaosong MengXiaosong Meng More articles by this author , Sidney RobertsSidney Roberts More articles by this author , Hamed AhmadiHamed Ahmadi More articles by this author , Jeffrey HowardJeffrey Howard More articles by this author , Iftach ChaplinIftach Chaplin More articles by this author , Aditya BagrodiaAditya Bagrodia More articles by this author , Vitaly MargulisVitaly Margulis More articles by this author , Solomon WolduSolomon Woldu More articles by this author , Yair LotanYair Lotan More articles by this author , and Siamak DaneshmandSiamak Daneshmand More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002107.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Previous studies have demonstrated the benefit of blue light flexible cystoscopy (BLFC) in clinical practice though detection of additional cancers missed with white light cystoscopy (WLC) alone. However, the utility of BLFC for surveillance in patients receiving intravesical treatments has not been extensively studied. Identifying early recurrences in these patients can result in better stratification and possibly improved outcomes. Herein, we aim to evaluate the utility of BLFC for surveillance of bladder cancer post intravesical therapy. METHODS: Clinicopathologic information was collected from consecutive patients undergoing office-based BLFC who were enrolled in the Cysview registry between May 2018 and December 2020 at two high volume academic centers. Patients with last intravesical treatment >1 year were excluded. Data were stratified based on the time from last intravesical treatment. RESULTS: A total of 277 BLFC were performed in 136 patients (mean age 73 years). 85% were male, 61% had history of smoking and 30% had ³2 prior bladder cancer recurrences. 74% had high grade (HG) disease and the highest stage prior to BLFC was Ta, T1, carcinoma in situ (CIS), and Ta/T1+CIS in 40%, 34%, 17% and 9%, respectively.Intravesical Bacillus Calmette–Guérin (BCG) and intravesical chemotherapy were used in 83% and 17%, respectively. WLC and BLFC were both normal in 162 (58.5%) procedures. WLC or BLFC was abnormal in 40% of post BCG and 37% of post intravesical chemotherapy cystoscopies.A total of 52 office biopsy were taken, of which, 23/52 (44%) were malignant (Table 1). BLFC was abnormal in all positive biopsies, while only 3/23 had positive or atypical cytology. BLFC was 100% sensitive for detection of cancer in this cohort. WLC was normal and BLFC was abnormal in 23 (8%) procedures. Of these, 16/23 had office-based biopsy and cancer was detected in 9/16. BLFC had the highest false positive rate at <6 weeks post intravesical therapy. CONCLUSIONS: Office-based BLFC helps improve early detection of recurrence in cases with normal WLC. BLFC can help in surveillance of patients receiving intravesical therapy, improve performance of office-based biopsy and increase early detection of BCG unresponsive disease. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1138-e1139 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sanam Ladi Seyedian More articles by this author Xiaosong Meng More articles by this author Sidney Roberts More articles by this author Hamed Ahmadi More articles by this author Jeffrey Howard More articles by this author Iftach Chaplin More articles by this author Aditya Bagrodia More articles by this author Vitaly Margulis More articles by this author Solomon Woldu More articles by this author Yair Lotan More articles by this author Siamak Daneshmand More articles by this author Expand All Advertisement Loading ...

PD51-10 COMPETING MORTALITY IN BLADDER CANCER PATIENTS AFTER CYSTECTOMY: THE ROLE OF SECOND NON-UROTHELIAL CANCERS

You have accessJournal of UrologyBladder Cancer: Invasive III (PD51)1 Sep 2021PD51-10 COMPETING MORTALITY IN BLADDER CANCER PATIENTS AFTER CYSTECTOMY: THE ROLE OF SECOND NON-UROTHELIAL CANCERS Patrick Hensley, Zhigang Duan, Kelly Bree, Akshay Sood, Andrea Kokorovic, Hui Zhao, Charles Guo, Neema Navai, Colin Dinney, and Ashish Kamat Patrick HensleyPatrick Hensley More articles by this author , Zhigang DuanZhigang Duan More articles by this author , Kelly BreeKelly Bree More articles by this author , Akshay SoodAkshay Sood More articles by this author , Andrea KokorovicAndrea Kokorovic More articles by this author , Hui ZhaoHui Zhao More articles by this author , Charles GuoCharles Guo More articles by this author , Neema NavaiNeema Navai More articles by this author , Colin DinneyColin Dinney More articles by this author , and Ashish KamatAshish Kamat More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002078.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Muscle-invasive bladder cancer (MIBC) is associated with considerable disease- and treatment-related morbidity and mortality and is often diagnosed in heavily co-morbid patients. With improved surgical techniques and therapeutic options, survivorship in MIBC patients is of emerging relevance. We investigate the role of second non-urothelial cancer (SNUC) as a competing mortality risk factor in post-radical cystectomy (RC) patients. METHODS: An IRB-approved study of patients who underwent RC for cT2-3 MIBC from 2005-2018 was performed. The site and timing of biopsy-proven SNUC was recorded. Patients with less than 24-months of post-operative follow-up, those with non-melanoma cutaneous malignancies, and incidental prostate cancer were excluded. The cumulative incidence of SNUC and mortality were estimated with modified Kaplan-meier analysis. RESULTS: Median follow-up time for the 468 patients who underwent RC was 5.0 years (IQR 3.4-7.1 years). SNUC developed in 70 (15.0%) patients at a median 3.0 years (IQR 1.3-5.5 years) from RC with a cumulative incidence of SNUC at 3, 5 and 10 years after RC 7.2%, 11.4% and 23.5%, respectively. The most common sites for SNUC were lung (N=20, 4.3%) and hematologic malignancies (N=15, 3.2%). Bladder cancer surveillance imaging identified 70.0% of lung cancers and 62.5% of gastrointestinal cancers. Compared to lung cancers identified during symptomatic workup, those found on surveillance were more commonly stage 1 (78.6% vs. 16.7%, p=0.018) and non-lethal (64.3% vs. 16.6%, p=0.141). Bladder cancer mortality was surpassed by other-cause mortality as the leading cause of death 8 years after RC (Figure). The 15-year cumulative risk of mortality was: 21.0% for bladder cancer (95% CI 13.1%-30.1%), 10.5% for SNUC (95% CI 6.5%-15.7%), and 34.5% for other-cause (95% CI 21.6%-47.7%). CONCLUSIONS: SNUC developed in 15% of post-RC patients, with the majority identified on surveillance imaging. Other-cause mortality surpassed that of bladder cancer mortality in year 8 after RC. These data have clinical significance with regards to patient counseling, survivorship and oncologic surveillance in the highly co-morbid MIBC population. Source of Funding: Urology Care Foundation Research Scholars Award to PJH (IRG 85-001-25); Wayne B. Duddlesten Professorship and the Raymond and Maria Floyd Bladder Cancer Research Foundation Grant to AMK © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e909-e909 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Patrick Hensley More articles by this author Zhigang Duan More articles by this author Kelly Bree More articles by this author Akshay Sood More articles by this author Andrea Kokorovic More articles by this author Hui Zhao More articles by this author Charles Guo More articles by this author Neema Navai More articles by this author Colin Dinney More articles by this author Ashish Kamat More articles by this author Expand All Advertisement Loading ...

Alternating Cystoscopy with Bladder EpiCheck® in the Surveillance of Low-Grade Intermediate-Risk NMIBC: A Cost Comparison Model.

Bladder cancer surveillance is invasive, intensive and costly. Patients with low grade intermediate risk non-muscle invasive bladder cancer (NMIBC) are at high risk of recurrence. The objective of this model is to compare the cost of a strategy to alternate surveillance with cystoscopy and a urine marker, Bladder EpiCheck, to standard surveillance. A decision tree model was built using TreeAge Pro Healthcare to compare standard surveillance (Standard) with a modified surveillance incorporating Bladder EpiCheck. The model was based on 2 years of surveillance. Outcomes were obtained from literature. Costs were obtained from US and 9 European countries. Sensitivity analyses were performed. The efficacy of the model was equivalent in terms of recurrence for each arm with median recurrence rate of 22%. When setting marker price at 200 local currency, the marker arm was less expensive in the USA, Netherlands, Switzerland, Belgium, Italy, Austria and UK by 154€ to 329£ per patient, for a 2-year period. Cost was higher in France, Spain, and Germany by 33-103€. Cost parity was achieved with marker price between 148€ and $421. Marker cost and specificity have the greatest impact on the overall model cost. A strategy alternating the urine marker Bladder EpiCheck with cystoscopy in the surveillance of patients with low grade intermediate risk bladder cancer is cost equivalent in the US and European countries when the marker is priced 148€ -$421, as a result of the marker's high specificity (86%). Prospective studies will be necessary to validate these findings.

Determinants of Risk-Aligned Bladder Cancer Surveillance-Mixed-Methods Evaluation Using the Tailored Implementation for Chronic Diseases Framework.

For many patients with cancer, the frequency of surveillance after primary treatment depends on the risk for cancer recurrence or progression. Lack of risk-aligned surveillance means too many unnecessary surveillance procedures for low-risk patients and not enough for high-risk patients. Using bladder cancer as an example, we examined whether practice determinants differ between Department of Veterans Affairs sites where risk-aligned surveillance was more (risk-aligned sites) or less common (need improvement sites). We used our prior quantitative data to identify two risk-aligned sites and four need improvement sites. We performed semistructured interviews with 40 Veterans Affairs staff guided by the Tailored Implementation for Chronic Diseases framework that were deductively coded. We integrated quantitative data (risk-aligned site v need improvement site) and qualitative data from interviews, cross-tabulating salient determinants by site type. There were 14 participants from risk-aligned sites and 26 participants from need improvement sites. Irrespective of site type, we found a lack of knowledge on guideline recommendations. Additional salient determinants at need improvement sites were a lack of resources ("the next available without overbooking is probably seven to eight weeks out") and an absence of routines to incorporate risk-aligned surveillance ("I have my own guidelines that I've been using for 35 years"). Knowledge, resources, and lack of routines were salient barriers to risk-aligned bladder cancer surveillance. Implementation strategies addressing knowledge and resources can likely contribute to more risk-aligned surveillance. In addition, reminders for providers to incorporate risk into their surveillance plans may improve their routines.

Performance of Narrow Band Imaging (NBI) and Photodynamic Diagnosis (PDD) Fluorescence Imaging Compared to White Light Cystoscopy (WLC) in Detecting Non-Muscle Invasive Bladder Cancer: A Systematic Review and Lesion-Level Diagnostic Meta-Analysis.

Simple SummaryBladder cancer is one of the most common malignancies in the United States with a majority of patients diagnosed with non-muscle invasive bladder cancer (NMIBC). Despite early detection and regular surveillance of most cases, recurrence and progression rates remain high. The aim of our systematic review and meta-analysis was to compare the sensitivity, specificity, and oncologic outcomes of photodynamic diagnosis (PDD) fluorescence, narrow band imaging (NBI), and conventional white light cystoscopy (WLC) in detecting NMIBC. Through the collection of prospective and randomized controlled trials, we demonstrated that tumor resection with either PDD and NBI exhibited greater diagnostic sensitivity compared to WLC alone. Our findings underscore the value of integrating these enhanced technologies as a part of the standard care for patients with suspected or confirmed NMIBC.Despite early detection and regular surveillance of non-muscle invasive bladder cancer (NMIBC), recurrence and progression rates remain exceedingly high for this highly prevalent malignancy. Limited visualization of malignant lesions with standard cystoscopy and associated false-negative biopsy rates have been the driving force for investigating alternative and adjunctive technologies for improved cystoscopy. The aim of our systematic review and meta-analysis was to compare the sensitivity, specificity, and oncologic outcomes of photodynamic diagnosis (PDD) fluorescence, narrow band imaging (NBI), and conventional white light cystoscopy (WLC) in detecting NMIBC. Out of 1,087 studies reviewed, 17 prospective non-randomized and randomized controlled trials met inclusion criteria for the study. We demonstrated that tumor resection with either PDD and NBI exhibited lower recurrence rates and greater diagnostic sensitivity compared to WLC alone. NBI demonstrated superior disease sensitivity and specificity as compared to WLC and an overall greater hierarchical summary receiver operative characteristic. Our findings are consistent with emerging guidelines and underscore the value of integrating these enhanced technologies as a part of the standard care for patients with suspected or confirmed NMIBC.

Active surveillance for recurrent non-muscle invasive bladder cancer: which lessons have we learned during COVID-19 pandemic?

article: Active surveillance for recurrent non-muscle invasive bladder cancer: which lessons have we learned during COVID-19 pandemic? - Minerva Urology and Nephrology 2022 February;74(1):1-4 - Minerva Medica - Journals

Diagnostic and prognostic role of BTA, NMP22, survivin and cytology in urothelial carcinoma.

BackgroundCytology is a recommended noninvasive urine test for the detection and surveillance of bladder cancer and upper-tract urothelial carcinoma. It is however characterized by poor sensitivity in low-grade tumors. This study aims to determine the diagnostic and prognostic role of BTA, BTA-stat, NMP22, and Survivin.MethodsUrine samples were collected from a total of 105 patients (bladder cancer (n=61), upper-tract urothelial carcinoma (n=44), and controls (n=52). The samples were directly assessed using cytology, BTA-stat (Qualitative test), BTA (chemiluminescence test), NMP22 (Qualitative test), and Survivin (enzyme-linked immunosorbent assay). Cancer progression and recurrence were assessed after a median follow-up of 32 months (4–47 months). Univariate and multivariate analyses were performed using Kaplan-Meier survival analysis and Cox proportional hazards regression.ResultsThe triple combination of Survivin + BTA + Cytology was the most promising model for discriminating bladder cancer or upper-tract urothelial carcinoma from controls (UTUC group: the area under the curve value 0.97, sensitivity 86%, specificity 96%; BC group: the area under the curve value 0.86 sensitivity 67%, specificity 96%). Univariate survival analysis, showed Cytology (P=0.02; HR=5.35) and Survivin (HR=3.24; P=0.03) to have a significant association with the progression-free survival, while Survivin (HR=4.15; P=0.04) was statistically associated with cancer-specific survival in the bladder cancer group. The multivariable analysis did not show any of these markers as independent prognostic factors.ConclusionsThese biomarkers showed a higher sensitivity than cytology, but a poorer specificity. All biomarkers exhibited good diagnostic performance in both bladder cancer and upper-tract urothelial carcinoma. Combining Survivin + BTA + Cytology was superior to the use of a single marker or combining other biomarkers.

Reply by Authors.

No AccessJournal of UrologyAdult Urology1 Jul 2021Reply by Authorsis a reply to letterEditorial Comment Abhishek Bhat, Deukwoo Kwon, Nachiketh Soodana-Prakash, Ali Mouzannar, Sanoj Punnen, Mark L. Gonzalgo, Dipen J. Parekh, and Chad R. Ritch Abhishek BhatAbhishek Bhat Department of Urology, University of Miami Miller School of Medicine, Miami, Florida More articles by this author , Deukwoo KwonDeukwoo Kwon Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, Florida Biostatistics and Bioinformatics Shared Resource, Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida More articles by this author , Nachiketh Soodana-PrakashNachiketh Soodana-Prakash Department of Urology, University of Miami Miller School of Medicine, Miami, Florida More articles by this author , Ali MouzannarAli Mouzannar Department of Urology, University of Miami Miller School of Medicine, Miami, Florida More articles by this author , Sanoj PunnenSanoj Punnen Department of Urology, University of Miami Miller School of Medicine, Miami, Florida Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida More articles by this author , Mark L. GonzalgoMark L. Gonzalgo Department of Urology, University of Miami Miller School of Medicine, Miami, Florida Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida More articles by this author , Dipen J. ParekhDipen J. Parekh Department of Urology, University of Miami Miller School of Medicine, Miami, Florida Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida More articles by this author , and Chad R. RitchChad R. Ritch *Correspondence: Department of Urology, University of Miami Miller School of Medicine, 1120 NW 14th St., Miami, Florida 33136 (FAX: 305-243-6597; E-mail Address: [email protected] Department of Urology, University of Miami Miller School of Medicine, Miami, Florida Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001689.02AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Reply by Authors." The Journal of Urology, 206(1), pp. 27–28 Reference 1. : Active surveillance for low risk nonmuscle invasive bladder cancer: a confirmatory and resource consumption study from the BIAS project. J Urol 2018; 199: 401. Link, Google Scholar CRR is a member of the AUA/SUO Joint Non-Muscle Invasive Guidelines Committee. © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsRelated articlesJournal of UrologyApr 9, 2021, 12:00:00 AMEditorial Comment Volume 206Issue 1July 2021Page: 27-28 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Abhishek Bhat Department of Urology, University of Miami Miller School of Medicine, Miami, Florida More articles by this author Deukwoo Kwon Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, Florida Biostatistics and Bioinformatics Shared Resource, Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida More articles by this author Nachiketh Soodana-Prakash Department of Urology, University of Miami Miller School of Medicine, Miami, Florida More articles by this author Ali Mouzannar Department of Urology, University of Miami Miller School of Medicine, Miami, Florida More articles by this author Sanoj Punnen Department of Urology, University of Miami Miller School of Medicine, Miami, Florida Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida More articles by this author Mark L. Gonzalgo Department of Urology, University of Miami Miller School of Medicine, Miami, Florida Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida More articles by this author Dipen J. Parekh Department of Urology, University of Miami Miller School of Medicine, Miami, Florida Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida More articles by this author Chad R. Ritch Department of Urology, University of Miami Miller School of Medicine, Miami, Florida Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida *Correspondence: Department of Urology, University of Miami Miller School of Medicine, 1120 NW 14th St., Miami, Florida 33136 (FAX: 305-243-6597; E-mail Address: [email protected] More articles by this author Expand All CRR is a member of the AUA/SUO Joint Non-Muscle Invasive Guidelines Committee. Advertisement PDF DownloadLoading ...

Differentially Expressed Extracellular Vesicle-Contained microRNAs before and after Transurethral Resection of Bladder Tumors.

Bladder cancer (BC) is currently diagnosed and monitored by cystoscopy, a costly and invasive procedure. Potential biomarkers in urine, blood, and, more recently, extracellular vesicles (EVs), have been explored as non-invasive alternatives for diagnosis and surveillance of BC. EVs are nanovesicles secreted by most cell types containing diverse molecular cargo, including different types of small RNAs, such as microRNA (miRNA). In this study, we performed next-generation sequencing of EV-contained miRNA isolated from urine and serum of 41 patients with non-muscle invasive BC (27 stage Ta, 14 stage T1) and 15 non-cancer patients (NCP) with benign cystoscopy findings. MiRNA sequencing was also performed on serum supernatant samples for T1 patients. To identify potential BC-specific biomarkers, expression levels of miRNA in presurgery samples were compared to those at postsurgery check-ups, and to NCPs. Results showed that two miRNAs, urinary EV-contained miR-451a and miR-486-5p, were significantly upregulated in presurgery samples from T1 patients compared to postsurgery check-up samples. This was confirmed in a replica EV/RNA isolation and sequencing run of 10 T1 patients from the primary run; however, analyses revealed no differential expression of miRNAs in serum EVs, serum supernatant, or when comparing BC patients to NCPs. This is the first study to investigate EV-containing miRNA sequencing in pre- and postsurgery BC patient samples and our findings suggest that urinary EV-contained miR-451a and miR-486-5p may be potential biomarkers for recurrence-free survival of BC patients with stage T1 disease.

Proteomic research and diagnosis in bladder cancer: state of the art review.

ABSTRACTPurpose:Proteomic biomarkers have been emerging as alternative methods to the gold standard procedures of cystoscopy and urine cytology in the diagnosis and surveillance of bladder cancer (BC). This review aims to update the state of the art of proteomics research and diagnosis in BC.Materials and Methods:We reviewed the current literature related to BC research on urinary, tissue, blood and cell line proteomics, using the Pubmed database.Findings:Two urinary protein biomarkers are FDA-approved (NMP22® and BTA® tests), only if performed along with cystoscopy for surveillance after initial diagnosis, but not in the primary diagnostic setting due to high false-positive rates in case of infections, stones and hematuria. There are a great number of non-FDA approved proteins being studied, with good preliminary results; panels of proteins seem valuable tools to be refined in ongoing trials. Blood proteins are a bigger challenge, because of the complexity of the serum protein profile and the scarcity of blood proteomic studies in BC. Previous studies with the BC tissue proteome do not correlate well with the urinary proteome, likely due to the tumor heterogeneity. Cell line proteomic research helps in the understanding of basic mechanisms that drive BC development and progression; the main difficulty is culturing low-grade tumors in vitro, which represents the majority of BC tumors in clinical practice.Conclusion:Protein biomarkers have promising value in the diagnosis, surveillance and prognostic of BC. Urine is the most appropriate body fluid for biomarker research in BC due to its easiness of sampling, stability and enrichment of shed and secreted tumor-specific proteins. Panels of biomarkers may exhibit higher sensitivity than single proteins in the diagnosis of BC at larger populations due to clinical and tumor heterogeneity. Prospective clinical trials are warranted to validate the relevance of proteomic data in the clinical management of BC.

Quality of life in patients undergoing surveillance for non-muscle invasive bladder cancer-a systematic review.

BackgroundThe main objective of this study was to evaluate the various instruments available to evaluate the quality of life (QoL) in patients diagnosed with non-muscle invasive bladder cancer (NMIBC) undergoing surveillance.MethodsA PubMed literature review was carried out with query terms (“Urinary Bladder Neoplasms” [Mesh] OR “Bladder malignancy”) AND (“quality of life”) including all studies up to June 2020. This resulted in 576 peer-reviewed articles. A further 12 articles from additional sources were included. A total of 473 articles were eliminated due to lack of relevance to the topic of concern. A further 93 articles evaluating NMIBC and articles evaluating Radiotherapy were excluded and a total of 22 studies were studied.ResultsIn total, 22 studies were identified. The vast majority of studies were prospective descriptive studies (n=9), while there were 7 cross-sectional surveys and 6 randomised controlled trials. Most studies evaluated the impact of intravesical treatment on QoL. NMIBC survivors had significantly lower QoL compared to the general population, Surveillance strategies involving repeated intravesical therapies and cystoscopies have a negative impact on QoL with impaired physical function and mental health.ConclusionsThis article emphasizes the importance of assessing the QoL in patients with NMIBC undergoing long term surveillance, as they represent the majority of bladder cancer patients. Development and validation of specific instruments to measure QoL in patients with NMIBC are desperately needed to assess, better understand, and manage the burden of disease and healthcare in this group of patients.

P0752 - Xpert bladder monitor: Longitudinal clinical performance for avoiding un-necessary cystoscopies in patients under active surveillance for recurrent bladder cancer (BIAS project)

P0752 - Xpert bladder monitor: Longitudinal clinical performance for avoiding un-necessary cystoscopies in patients under active surveillance for recurrent bladder cancer (BIAS project)

Trends in urine biomarker discovery for urothelial bladder cancer: DNA, RNA, or protein?

Urothelial bladder cancer is a complex disease displaying a landscape of heterogenous molecular subtypes, mutation profiles and clinical presentations. Diagnosis and surveillance rely on flexible cystoscopy which has high accuracy, albeit accompanied by a high-cost burden for healthcare providers and discomfort for patients. Advances in “omic” technologies and computational biology have provided insights into the molecular pathogenesis of bladder cancer and provided powerful tools to identify markers for disease detection, risk stratification, and predicting responses to therapy. To date, numerous attempts have been made to discover and validate diagnostic biomarkers that could be deployed as an adjunct to the cystoscopic diagnosis and long-term surveillance of bladder cancer. We report a comprehensive literature analysis using PubMed to assess the changing trends in investigating DNA, RNA, or proteins as diagnostic urinary biomarkers over a period of 5 decades: 1970–2020. A gradual shift has been observed in research away from protein biomarkers to nucleic acids including different classes of RNA, and DNA methylation and mutation markers. Until 2000, publications involving protein biomarker discovery constituted 87% of the total number of research articles with DNA comprising 6% and RNA 7%. Since 2000 the proportion of protein biomarker articles has fallen to 40%, and DNA and RNA studies increased to 32% and 28%, respectively. Clearly research focus, perhaps driven by technological innovation, has shifted from proteins to nucleic acids. We optimistically hypothesise that, following thorough validation, a clinically useful detection test for bladder cancer based on a panel of DNA or RNA markers could become reality within 5–10 years.

Endoscopic surveillance for bladder cancer: a systematic review of contemporary worldwide practices.

BackgroundThe aim of this systematic review was to identify the current endoscopic surveillance strategies in use across the world and to determine whether these were sufficient or if any recommendations for changes in the guidelines could be made. This review focused on the cystoscopic follow-up of non-muscle invasive bladder cancer (NMIBC) patients and muscle invasive bladder cancer (MIBC) patients who had undergone bladder sparing treatments.MethodsA literature search was carried out on Medline and Embase using OVID gateway according to a pre-defined protocol. Systematic screening of the identified studies was carried out by two authors. Quality assessment was performed using the Joanna Briggs critical appraisal tools. Data was extracted on various aspects including the follow-up regime utilised, patients included, outcomes investigated and a summary of the results. The studies were compared in a narrative nature.ResultsA total of 2,604 studies were identified from the search strategy, of which 14 were deemed suitable for inclusion following the screening process. The studies identified were from nine countries and were mainly observational or qualitative. There was a huge variation in the follow-up regimes utilised within the studies with no clear consensus as to which regime was the most suitable. However, all studies utilised an initial cystoscopy at three months post-TURBT. No studies were identified which investigated the endoscopic follow-up strategies for MIBC patients who opted for bladder conservation with chemoradiation.ConclusionsThere is no universally accepted protocol for endoscopic follow-up of patients with NMIBC bladder cancer. Guidance on cystoscopic monitoring of bladder in patients who have undergone chemoradiation for MIBC is also lacking.

Comparing CxBladder to Urine Cytology as Adjunct to Cystoscopy in Surveillance of Non-muscle Invasive Bladder Cancer-A Pilot Study.

Purpose: Guidelines advocate cystoscopy surveillance (CS) for non-muscle invasive bladder cancer (NMIBC) post-resection. However, cystoscopy is operator dependent and may miss upper tract lesions or carcinoma in-situ (CIS). Urine cytology is a common adjunct but lacks sensitivity and specificity in detecting recurrence. A new mRNA biomarker (CxBladder) was compared with urine cytology as an adjunct to cystoscopy in detecting a positive cystoscopy findings during surveillance cystoscopy in our center.Materials and Methods: Consented patients older than 18, undergoing CS for NMIBC, provide paired urine samples for cytology and CxBladder test. Patients with positive cystoscopy findings would undergo re-Trans Urethral Resection of Bladder Tumor (TURBT).Results: Thirty-five patients were enrolled from April to June 2019. Seven contaminated urine samples were excluded. The remaining cohort of 23 (82%) and 5 (18%) females had a mean age of 66.69 (36–89). Eight (29%) patients with positive cystoscopy finding underwent TURBT. All 8 patients also had positive CxBladder result. This shows that CxBladder has a sensitivity and negative predictive value (NPV) of 100%, specificity of 75% and positive predictive value (PPV) of 62% in predicting a positive cystoscopy finding. TURBT Histo-pathological findings showed Low-grade Ta NMIBC in one patient (4%), and 7 (25%) patients had inflammatory changes. Urine cytology was only positive in one patient with a positive cystoscopy finding. This led to a sensitivity of merely 13% and NPV of 74%, while specificity and PPV was 100% in predicting a positive cystoscopy finding.Conclusion: CxBladder had high NPV and sensitivity which accurately predicted suspicious cystoscopy findings leading to further investigation. It has great potential for use as adjunct to cystoscopy for surveillance of NMIBC.

The use of artificial intelligence for the diagnosis of bladder cancer: a review and perspectives.

White light cystoscopy is the current standard for primary diagnosis and surveillance of bladder cancer. However, cancer changes can be subtle and may be easily missed. With the advancement of deep learning (DL), image recognition by artificial intelligence (AI) proves a high accuracy for image-based diagnosis. AI can be a solution to enhance bladder cancer diagnosis on cystoscopy. An algorithm that classifies cystoscopic images into normal and tumour images is essential for AI cystoscopy. To develop this AI-based system requires a training dataset, an appropriate type of DL algorithm for the learning process and a specific outcome classification. A large data volume with minimal class imbalance, data accuracy and representativeness are pre-requisite for a good dataset. Algorithms developed during the past two years to detect bladder tumour achieved high performance with a pooled sensitivity of 89.7% and specificity of 96.1%. The area under the curve ranged from 0.960 to 0.980, and the accuracy ranged from 85.6 to 96.9%. There were also favourable results in the various attempts to enhance detection of flat lesions or carcinoma-in-situ. AI cystoscopy is a possible solution in clinical practice to enhance bladder cancer diagnosis, improve tumour clearance during transurethral resection of bladder tumour and detect recurrent tumours upon surveillance.

Hexylaminolevulinate-mediated fluorescent urine cytology with a novel automated detection technology for screening and surveillance of bladder cancer.

To evaluate the diagnostic performance of fluorescent voided urine cytology (FVUC) using a novel automated detection technology to screen for primary bladder cancer and for surveillance of recurrent bladder tumour. We created a rapid, objective, automated, and high-throughput detection device for hexylaminolevulinate-mediated FVUC, named the cellular fluorescence analysis unit-II (CFAU-II). Two different cohorts were used in this study: (i) screening test for primary bladder cancer (165 patients with bladder cancer and 52 controls), and (ii) surveillance test for detecting intravesical recurrent tumour (192 patients with treated non-muscle-invasive bladder cancer and 15 with post-nephroureterectomy upper urinary tract cancer). Voided urine samples were subjected to urine analysis, conventional VUC (cVUC), and FVUC. Diagnostic performance was compared between cVUC, FVUC, and a combination of the two. A total of 614 urine samples were successfully collected, processed, and analysed. Comparative analysis of the screening test cohort demonstrated that the overall sensitivity of FVUC (63%, P<0.001) and combination testing (72%, P<0.001) was significantly higher than that of cVUC (29%). FVUC was found to be superior in most of the subgroups, especially in low-grade, Ta, and small tumours. Analysis of the surveillance test cohort showed that combination testing achieved a sensitivity of 82% and a negative predictive value of 98%, whereas those of cVUC were 39% and 96%, respectively. According to the pathological finding of recurrent tumours presenting false-negative result in the FVUC, the majority of the overlooked recurrent diseases were Ta low-grade tumours. Logistic regression analysis suggested an association between the risk of false-positive results and high density of urine white blood cells and alkaluria. The present findings clearly demonstrate that FVUC using the newly developed automation technology has superior sensitivity to cVUC for both screening for primary bladder cancer and recurrent tumour detection. It is essential to confirm the clinical usefulness of this method via further large-scale studies, in addition to ensuring its affordability and availability.

The use of an automated electronic registry for bladder cancer surveillance during the SARS-CoV-2 pandemic

Introduction: We aimed to develop and compare the utility of an automated registry of all patients undergoing surveillance for non-muscle invasive bladder cancer (NMIBC) during the severe acute respiratory virus coronavirus 2 (SARS-CoV-2) pandemic. Methods: We populated an electronic register of all patients undergoing bladder tumour surveillance (July–September 2019). The computerised ‘traffic-light’ system was implemented in September 2019 marking the beginning of phase 2. The register was audited at two- and six-months intervals during phase 2 (November 2019 and April 2020). Audit of the system In April 2020 allowed review of care given during the peak of the SARS-CoV-2 pandemic in Ireland. The primary outcome variable was the number of patients who had delayed surveillance cystoscopy in each group. Results: A total of 278 cases were reviewed, 96 in the first cohort and 91 at both intervals of second phase. During the first phase of the audit 17 patients (17.7%) had a missed cystoscopy. Phase 2 showed a sustained decrease in the number of patients with missed surveillance, with eight (8.8%) missing their procedure in both the November and April (SARS-CoV-2) cohorts (17 v. 8, X2 = 10.76, p = 0.0004). Overall, most patients had their procedure done within the recommended time interval (245, 88%). Conclusion: A centralised accessible computerised registry of patients with NMIBC undergoing surveillance is superior to traditional manual surveillance methods, especially during the period of SARS-CoV-2. Going forward we aim to have all patients undergo surveillance within schedule with a long-term goal of a centralised national registry. Level of evidence: Level 2c: “Outcomes Research”.