Discovery of bladder cancer biomarkers in paired pre- and postoperative urine samples

BackgroundBladder cancer (BC), a common cancer of the urinary system, has a low mortality but an extremely high recurrence rate. Patients who have undergone initial surgical treatment often undergo frequent prognostic examinations with a substantial burden of discomfort and costs. Urine samples can reflect early disease processes in the urinary system and may be an excellent source of biomarkers.MethodsIn the present study, we used the liquid chromatography with tandem mass spectrometry (LC-MS/MS) to perform proteomic analysis of pre- and postoperative urine samples from patients with stage III BC to identify biomarkers of cancer prognosis. Candidate biomarkers from proteomic analysis were simultaneously validated using western blotting in an independent cohort and immunohistochemical (IHC) staining, combined with gene expression data of BC samples in The Cancer Genome Atlas (TCGA).ResultsThe comparison of pre- and postoperative urine samples from the same patients led to the discovery of several significantly differentially expressed proteins, whose functions could be closely related to the occurrence and development of BC. We confirmed a representative group of candidate biomarker molecules, such as cadherin-related family member 2 (CDHR2), heat shock protein beta-1 (HSP27), and heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).ConclusionsThe candidate biomarker molecules can distinguish between pre- and postoperative urine samples, and alterations in their expression levels are significantly associated with recurrence rates in patients with BC. Therefore, these molecules may become useful biomarkers for the monitoring and prognosis of BC.     

Factores de riesgo constitucionales y ocupacionales asociados al cáncer vesical

ObjectiveBladder carcinoma (BC) is the fourth most common type of cancer in males from Western countries, with primary prevention an important healthcare challenge. We review the associated constitutional and occupational risk factors (RF), with greater or lesser scientific evidence, in the aetiology of BC.Material and methodsLiterature review of the last 25 years of the constitutional and occupational RF associated with BC, conducted on MedLine, CancerLit, Science Citation Index and Embase. The search profiles were Risk factors/Genetic factors/Genetic polymorphisms/Epidemiology/Occupational factors and Bladder cancer.ResultsThe main RF were a) age and gender (diagnosed at age 65 and over, with a 4:1 ratio of males to females); b) race, ethnicity and geographic location (predominantly in Caucasians and in Southern European countries); c) genetic (N-acetyltransferase-2 and glutathione s-transferase M1 gene mutations, which significantly increase the risk for BC); d) occupational, which represent 5%-10% of BC RF; and f) occupations with high BC risk, such as aluminium production, the manufacture of dyes, paints and colourings, the rubber industry and the extraction and industrial use of fossil fuels.ConclusionsBC is the end result of the variable combination of constitutional and environmental RF, the majority of which are unknown. The most significant constitutional RF are related to age, gender, race, ethnicity geographic location and genetic polymorphisms. The main occupational RF are those related to aromatic amines and polycyclic aromatic hydrocarbons.     

Attacking Key Performance Indicators in Soccer: Current Practice and Perceptions from the Elite to Youth Academy Level

Key Performance Indicators (KPIs) are used to evaluate the offensive success of a soccer team (e.g. penalty box entries) or player (e.g. pass completion rate). However, knowledge transfer from research to applied practice is understudied. The current study queried practitioners (n = 145, mean ± SD age: 36 ± 9 years) from 42 countries across different roles and levels of competition (National Team Federation to Youth Academy levels) on various forms of data collection, including an explicit assessment of twelve attacking KPIs. 64.3% of practitioners use data tools and applications weekly (predominately) to gather KPIs during matches. 83% of practitioners use event data compared to only 52% of practitioners using positional data, with a preference for shooting related KPIs. Differences in the use and value of metrics derived from positional tracking data (including Ball Possession Metrics) were evident between job role and level of competition. These findings demonstrate that practitioners implement KPIs and gather tactical information in a variety of ways with a preference for simpler metrics related to shots. The low perceived value of newer KPIs afforded by positional data could be explained by low buy-in, a lack of education across practitioners, or insufficient translation of findings by experts towards practice.Key points

• Soccer practitioners collect data and evaluate performance in a variety of ways depending on the level of competition and their role within a club or federation.
• Practitioners reported a preference for shooting related metrics gathered by event data compared to KPIs offered by optical positional tracking technology.
• Despite increased interest and the capability to measure contextual aspects of passing performance with tracking technology, most practitioners still rely on more easily computed metrics (e.g. Pass Completion Percentage) and ball possession KPIs (e.g. Total Duration of Possession).
• This study highlights a gap in knowledge transfer between research and practice, encouraging increased education and collaborative efforts between data/sport scientists and practitioners to progress the field of analytics towards practical use in soccer.

Key words: Football, soccer, match analysis, performance analysis, applied data-science     

Secondary gastric cancer malignancies following a breast cancer diagnosis: A population-based analysis

ObjectiveTo quantify the population-risk of developing gastric cancer (GC) following breast cancer (BC).MethodsGC incidence following a ductal or lobular BC were separately compared to incidence in the general United States population using SEER data.ResultsGC rates were similar to the general population for ductal BC. Women aged 35–75 with lobular BC had a significantly higher incidence of GC; women aged 40–44 had the highest risk.ConclusionThe risk of secondary GC is high among young women diagnosed with lobular BC. More studies investigating the etiology and prevalence of familial GC syndromes at the population-level are needed.     

Essential amino acids deprivation is a potential strategy for breast cancer treatment

AimsThe study aimed to search novel, simple and practical index reflecting the level of essential amino acids (EAAs) metabolism in breast cancer (BC), as well as to explore the effect of enhanced EAAs metabolism on the prognosis and immune microenvironment of BC, thus providing new evidence for the application of EAAs deprivation in the BC treatment.MethodsThe study includes the analysis of multi-omics and clinical data of 13 BC cell lines and 2898 BC patients in the public database. Further validation was performed using multi-omics and immunohistochemistry data from 83 BC tissue samples collected at our hospital.ResultsAccording to the multi-omics data, the SLC7A5 to SLC7A8 Ratio (SSR) score was found to be significantly correlated with the EAAs level and EAAs-metabolic activity of BC, suggesting that the SSR score might be used as a biomarker to assess the degree of EAAs metabolism in BC. Besides, BC patients with high EAAs metabolism had shorter overall survival (OS) time, higher PD-L1 expression, and higher T regulatory cells (Tregs) infiltration, indicating that a high EAAs metabolism was related to a poor prognosis and immune suppression in BC. Additionally, MYC amplification is a critical molecular process in the metabolic reprogramming of EAAs in BC.ConclusionEAAs may be a possible therapeutic target for BC treatment.     

Cost-utility analysis in orthopaedic trauma; what pays? A systematic review

BackgroundAs healthcare systems come under ever-increasing pressure to provide more care with fewer resources, emphasis is being placed on value-based systems that maximise quality and minimize cost. The aim of this study was to determine which interventions in fracture care have been demonstrated to be cost effective.MethodsA systemic review of cost-utility studies on the management of fractures from 1976 to 2015 was carried out using a search of the Cost-Effectiveness Analysis Registry, National Health Service Economic Evaluation Database (NHS EED) and MEDLINE.Results20 studies were included with 15 (75%) studies assessing interventions in lower limb trauma and 8 (25%) studies assessing interventions in upper limb trauma. 50% of studies used a decision tree model and 50% used collected data alongside a randomised clinical trial. Interventions which were shown to be cost effective in lower limb trauma were total hip replacement in displaced femoral neck fractures, the SHS in stable (A1 and A2) fractures and IM nailing for unstable (A3) fractures, salvage treatment for grade IIIB and IIIC open tibial fractures and operative treatment of ankle and calcaneal fractures. For systems-based strategies, there is evidence demonstrating cost effectiveness to treating hip fractures in high volume centres and to having resources in place to facilitate fractures being treated within 48 h of injury. In upper limb trauma there was evidence showing operative treatment of displaced proximal humerus fractures to be neither clinically nor cost effective. There was evidence supporting the operative treatment of non-displaced scaphoid fractures. Overall the quality of the studies was poor with only 50% (10) of studies able to make a treatment recommendation. Reasons for this included poor quality primary source data and poor reporting methodological practices.ConclusionCertain aspects of fracture management have been shown to be cost effective. However, there is a paucity of evidence in this area and further research is required so that value-based interventions are chosen by healthcare providers engaged in orthopaedic trauma care.     

Reproductive risk factors associated with breast cancer in young women by molecular subtype

BackgroundFew studies have examined detailed features of pregnancy and the postpartum period as potential risk factors for early onset breast cancer (BC) by molecular subtype. These data may have value for improving risk assessment and prevention.MethodsWe surveyed parous enrollees in the prospective Mayo Clinic Breast Disease Registry (MCBDR) who had been diagnosed with BC at age <55 years between 2015 and 2020. Summary statistics were used to describe survey responses and reproductive risk factors by BC subtype (defined by estrogen/progesterone receptors and human epidermal growth factor receptor expression, nurse-abstracted from the medical record). Associations were assessed with Kruskal-Wallis and Chi-Square tests, followed by age-adjusted linear and logistic regression models. We compared results from this parous cohort to those from a separate cohort of nulliparous MCBDR participants with BC diagnosed at age <55 years.ResultsIn 436 parous respondents with subtype data abstracted, we identified a higher frequency of BRCA1 mutation, earlier age at diagnosis, and lower BI in patients with triple negative BC. Comparing parous to nulliparous young women with breast cancer, the proportion with TNBC was larger in the latter (12.2% vs. 15.1%, p = 0.03).ConclusionsEarly age at diagnosis and deleterious BRCA1 mutation were more frequent among TNBC patients. In addition, parous young women with TNBC had a lower BI than those with other BC subtypes, a hypothesis-generating finding that supports the need for additional research on the cycle of pregnancy-lactation-postpartum involution and BC etiology.     

Real world patterns of care in HER2-overexpressing breast cancer: Results of a survey of TEACH clinical trial investigators in 2011

BackgroundHER2-overexpressing breast cancer (BC) is common among young patients and poses a public health burden. Adjuvant anti-HER2/neu therapy with trastuzumab reduces the risk of recurrence and improves survival.MethodsA web-based survey was sent to 386 physicians of the “TEACH” trial in 2011 to determine access to HER2/neu testing and treatment patterns for HER2-overexpressing BC.ResultsThere were 151 responders (39%) from 28 countries. Ninety-seven percent reported HER2/neu expression is routinely measured in their institutions by immunohistochemistry (85%), FISH (80%) and other methods (16%). Twenty percent of responders from Asia reported that the test was not routinely available. Forty-eight percent of participants reported instances when adjuvant HER2-directed therapy was recommended to a patient who eventually did not receive it. Reasons for not receiving trastuzumab was cost (73%, p < 0.0001) in low- and middle-income countries and co-morbidities in high-income countries (43%, p = 0.003).ConclusionsThis survey reflects the availability of HER2/neu testing and anti-HER2/neu therapy among physicians who participated in TEACH. A high proportion of women with HER2-overexpressing BC may not receive standard adjuvant therapy due to unavailability of the test and cost of therapy. Despite having some limitations, such as a possible selection bias of participating physicians, variable definitions of access to healthcare among respondents, and changes in trastuzumab availability since 2011, our results demonstrate that access to care and region of practice impact the implementation of cancer treatments.     

Plasma microRNA profiles for bladder cancer detection

BackgroundBladder cancer (BC) is a burdensome disease with significant morbidity, mortality, and cost. The development of novel plasma-based biomarkers for BC diagnosis and surveillance could significantly improve clinical outcomes and decrease health expenditures. Plasma miRNAs are promising biomarkers that have yet to be rigorously investigated in BC.ObjectiveTo determine the feasibility and efficacy of detecting BC with plasma miRNA signatures.Materials and methodsPlasma miRNA was isolated from 20 patients with bladder cancer and 18 noncancerous controls. Samples were analyzed with a miRNA array containing duplicate probes for each miRNA in the Sanger database. Logistic regression modeling was used to optimize diagnostic miRNA signatures to distinguish between muscle invasive BC (MIBC), non-muscle-invasive BC (NMIBC) and noncancerous controls.ResultsSeventy-nine differentially expressed plasma miRNAs (local false discovery rate [FDR] <0.5) in patients with or without BC were identified. Some diagnostically relevant miRNAs, such as miR-200b, were up-regulated in MIBC patients, whereas others, such as miR-92 and miR-33, were inversely correlated with advanced clinical stage, supporting the notion that miRNAs released in the circulation have a variety of cellular origins. Logistic regression modeling was able to predict diagnosis with 89% accuracy for detecting the presence or absence of BC, 92% accuracy for distinguishing invasive BC from other cases, 100% accuracy for distinguishing MIBC from controls, and 79% accuracy for three-way classification between MIBC, NIMBC, and controls.ConclusionsThis study provides preliminary data supporting the use of plasma miRNAs as a noninvasive means of BC detection. Future studies will be required to further specify the optimal plasma miRNA signature, and to apply these signatures to clinical scenarios, such as initial BC detection and BC surveillance.     

A pilot study of prospective memory functioning in early breast cancer survivors

AimsTo evaluate prospective memory (PM) functioning in early breast cancer (BC) survivors and its association with fatigue and depression.MethodsThe Memory for Intention Screening Test, the Center for Epidemiologic Studies Depression Scale and the Functional Assessment of Cancer Therapy-Fatigue subscale were administered to 80 patients and 80 aged-matched healthy controls.ResultsPatients performed more poorly than controls on the memory test (p < 0.001) and had a higher rate of impairment (odds ratio = 5.5, p < 0.01). Fatigue mediated the relationship between Group membership and PM performance.ConclusionsBC survivors exhibited a clear pattern of PM deficit and fatigue was a major contributor to this deficit. This suggests that a common mechanism may be involved in fatigue symptoms and memory disturbances experienced by patients. Further research is needed to evaluate the role of adjuvant therapy in PM deficits and to explore whether interventions targeted at improving fatigue may also improve memory functioning in BC survivors.     

Impact of subtypes and comorbidities on breast cancer relapse and survival in population-based studies

ObjectiveTo study the impact of subtypes and comorbidities on breast cancer (BC) relapse and survival in the heterogeneous patients of the real world.MethodsWe identified patients diagnosed with BC between January 2003 and December 2005 from six population-based Swiss cancer registries. Clinicopathologic data was completed with information on locoregional and distant relapse and date and cause of death for over 10-years. We approximated BC subtypes using grade and the immunohistochemical panel for oestrogen, progesterone and human epidermal growth factor 2 (HER2) receptor status. We studied factors affecting relapse and survival.ResultsLuminal A-like subtype represented 46% of all newly diagnosed BC (N = 1831), followed by luminal B-like (N = 1504, 38%), triple negative (N = 436, 11%) and HER2 enriched (N = 204, 5%). We observed regional disparities in subtype prevalence that contribute to explain regional differences in survival formerly described. Disease relapse and BC specific mortality differed by subtype and were lower for luminal A like tumours than for other subtypes for any stage at diagnosis. After a median follow-up of 10.9 years, 1311 (33%) had died, half of them 647 (16%) due to another disease, showing the importance of comorbidities. Omission of systemic therapies in selected patients was not associated with poorer BC specific survival, BC subtype and life expectancy playing a role.ConclusionsInformation on tumour subtype is necessary for an adequate interpretation of population-based BC studies. Measures of comorbidity or frailty help in the evaluation of quality of care in the highly heterogeneous patients of the real world.     

Reduction in advanced breast cancer after introduction of a mammography screening program in Tyrol/Austria

BackgroundWe analysed all female breast cancer (BC) cases in Tyrol/Austria regarding the shift in cancer characteristics, especially the shift in advanced BC, for the group exposed to screening as compared to the group unexposed to screening.MethodsThe analysis was based on all BC cases diagnosed in women aged 40–69 years, resident in Tyrol, and diagnosed between 2009 and 2013. The data were linked to the Tyrolean mammography screening programme database to classify BC cases as “exposed to screening” or “unexposed to screening”. Age-adjusted relative risks (RR) were estimated by relating the exposed to the unexposed group.ResultsIn a total of about 145,000 women aged 40–69 years living in Tyrol during the study period, 1475 invasive BC cases were registered. We estimated an age-adjusted relative risk (RR) for tumour size ≥ 21 mm of 0.72 (95% confidence interval (CI) 0.60 to 0.86), for metastatic BC of 0.27 (95% CI 0.17 to 0.46) and for advanced BC of 0.83 (95% CI 0.71 to 0.96), each comparing those exposed to those unexposed to screening, respectively.ConclusionIn our population-based registry analysis we observed that participation in the mammography screening programme in Tyrol is associated with a 28% decrease in risk for BC cases with tumour size ≥ 21 mm and a 17% decrease in risk for advanced BC. We therefore expect the Tyrolean mammography programme to show a reduction in BC mortality.     

Analysis of hOGG1 genotype as a prognostic marker for muscle invasive bladder cancer: a novel approach using peptide nucleic acid-mediated, real-time PCR clamping

ObjectiveDNA damage repair mechanisms are a source of genetic mutation and are believed to play an important role in human cancer. Human 8-oxoguanine DNA glycosylase 1 (hOGG1) is involved in the recognition and repair of DNA damage. The value of the hOGG1 genotype as a prognostic indicator for bladder cancer (BC) was assessed using a novel technological approach.Materials and methodsThe association between genetic polymorphisms of hOGG1 codon 326 and clinicopathologic characteristics of 337 patients with BC was analyzed using peptide nucleic acid (PNA)-mediated real-time PCR clamping.ResultsTumor grade and size were significantly associated with the hOGG1 codon 326 genotype in non-muscle-invasive bladder cancer (NMIBC). The Cys326Cys polymorphism was significantly associated with progression and cancer specific survival in patients with muscle-invasive bladder cancer (MIBC). Multivariate Cox regression analysis indicated that the hOGG1 Cys326Cys polymorphism is associated with a protective effect on progression and a more dominant survival benefit than the Ser326Ser polymorphism in MIBC (hazard ratio 0.284 and 0.305, respectively).ConclusionsAnalysis of genotypes and clinical data for 337 BC patients indicates that the hOGG1 genotype may be a useful prognostic genetic marker for MIBC.     

Barriers to sexual recovery in men with prostate,bladder and colorectal cancer

BackgroundSurvivors of prostate, bladder, and colorectal cancer endure many sexual side-effects of treatment that negatively impact their relationships and diminish their quality of life. Multiple barriers exist in addressing men's sexual concerns in oncological care.ObjectiveTo describe barriers of sexual recovery in men with prostate, bladder, and colorectal cancer.MethodsWe searched PubMed for peer-reviewed, English-language articles published from 1999 to 2019 using the following search terms: “prostate cancer,” or “bladder cancer,” or “colorectal cancer,” and “male,” and “sexual function,” or “sexual barrier” or “sexual dysfunction.” Criteria for inclusion consisted of peer-reviewed articles (review, cross-sectional, longitudinal, interventional, or pilot studies) addressing sexual issues in men with a history of prostate, bladder, or colorectal cancer.ResultsBarriers to sexual recovery in men with prostate, bladder, and colorectal cancer include psychosocial barriers such as the feeling of loss, grief, depression and anxiety, the poor utilization, and excessive cost of pro-erectile aids, a diminished sense of masculinity and reluctance to seek help for sexual problems, as well as poor couple coping. Barriers in healthcare also exist, as healthcare providers often do not effectively address sexual issues due to poor communication, lack of comfort in discussing sexual issues, time constraints, and patients’ hesitation to initiate discussions on sexual dysfunction. Patients with stomas and gay, bisexual, and queer men face additional challenges in their recovery of sexual intimacy. Barriers to sexual recovery are present in men during all stages of cancer and all modalities of treatment including surgery, radiation, or androgen deprivation therapy.ConclusionThere are multiple overlapping psychosocial and healthcare system barriers to sexual recovery after prostate, bladder, and colorectal cancer treatment. Oncological providers must be cognizant of these complex barriers so they can facilitate patients’ access to resources needed for successful sexual recovery after genitourinary cancer treatment. Evidence based interventions, such as couple psychosexual counseling and peer support should be implemented via multidisciplinary care.     

Pretreatment apparent diffusion coefficient does not predict therapy response to neoadjuvant chemotherapy in breast cancer

BackgroundSome reports indicated that apparent diffusion coefficient can predict pathologic response to treatment in breast cancer (BC). The purpose of the present meta-analysis was to provide evident data regarding use of ADC values for prediction of treatment response in BC.MethodsMEDLINE library, EMBASE and SCOPUS databases were screened for associations between ADC and treatment response for neoadjuvant chemotherapy in breast cancer (BC) up to March 2020. Overall, 22 studies met the inclusion criteria. For the present analysis, the following data were extracted from the collected studies: authors, year of publication, study design, number of patients/lesions, mean and standard deviation of the pretreatment ADC values. The methodological quality of the included studies was checked according to the QUADAS-2 instrument. The meta-analysis was undertaken by using RevMan 5.3 software. DerSimonian and Laird random-effects models with inverse-variance weights were used without any further correction to account for the heterogeneity between the studies. Mean ADC values including 95% confidence intervals were calculated separately for responders and non responders.ResultsThe acquired 22 studies comprised 1827 patients with different BC. Of the 1827 patients, 650 (35.6%) were reported as responders and 1177 (64.4%) as non-responders to the neoadjuvant chemotherapy. The pooled calculated pretreatment mean ADC value of BC in responders was 0.98 (95% CI = [0.94; 1.03]). In non-responders, it was 1.05 (95% CI = [1.00; 1.10]). The ADC values of the groups overlapped significantly.ConclusionPretreatment ADC alone cannot predict response to neoadjuvant chemotherapy in BC.     

What Has Changed in Patients Aged 65 and over Diagnosed with Breast Cancer during the COVID-19 Pandemic: A Single-Center Experience

IntroductionThe COVID-19 pandemic has a worldwide negative impact on healthcare systems. This study aims to determine how the diagnosis, clinicopathological features, and treatment approaches of patients with breast cancer (BC) diagnosed at ≥65 years old were affected during the pandemic. This survey has shown that patients, especially the elderly, had to postpone their BC health problems or delay their routine controls due to the risk of COVID-19 transmission, high mortality rates due to comorbidity, and restrictions.Materials and MethodsThe medical records of 153 patients with BC diagnosed at ≥65 years old before (January–December 2019; group A, n = 61) and during (March 2020–May 2021; group B, n = 92) the COVID-19 pandemic were retrospectively analyzed. In addition, clinicopathological features of patients, including age, admission form, clinical stage, tumor (T) size-grade-histology-subtype, lymph node involvement, surgery type, and treatment protocols, were evaluated.ResultsPatients mostly applied for screening purposes were included in group A and patients who frequently applied for diagnostic purposes due to their existing BC or other complaints were included in group B (p = 0.009). Group B patients had a higher clinical stage (p = 0.026) and had commonly larger (p = 0.020) and high-grade (p = 0.001) Ts. Thus, mastectomy and neoadjuvant systemic therapy were more commonly performed in group B (p = 0.041 and p = 0.005).ConclusionThe survey showed significant changes in BC diagnosis and treatment protocols for patients diagnosed at ≥65 years old during the COVID-19 pandemic. Postponing screening and delaying treatment leads to more advanced BC stages in elderly patients.     

Xpert bladder cancer monitor in surveillance of bladder cancer: Systematic review and meta-analysis

IntroductionThere is a need for sensitive and specific biomarkers for detecting recurrences in patients with non-muscle invasive bladder cancer (NMIBC) on surveillance. Xpert bladder cancer (BC) monitor is the latest rapid in vitro qualitative test that detects expression of 5 mRNAs using a GeneXpert instrument. The primary aim of this review was to systematically review and pool the data regarding the diagnostic performance of Xpert BC in patients with NMIBC.MethodsSystematic literature search using 4 electronic databases (PubMed, EMbase, Scopus and Web of science) was performed. Pooled sensitivity, specificity and diagnostic odds ratio (DOR) were estimated using DerSimonian-Laird random-effects model. Standard Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines were followed and the study protocol was registered with PROSPERO (CRD42021249762).ResultsIn this review, 11 prospective studies with 2,896 patients were included. Pooled sensitivity and specificity for Xpert BC were 73% (95% confidence interval (CI) 65%–80%) and 77% (95% CI 69%–84%) respectively. Area under curve (AUC) for Xpert BC monitor was 0.81 (0.78–0.84) respectively. Subgroup analysis from 7 studies for patients with high-grade recurrence revealed sensitivity, specificity and AUC of 0.86 (0.77–0.92), 0.78 (0.75–0.81) and 0.87 (0.84–0.90) respectively. Similar analysis for patients with low-grade recurrence revealed sensitivity, specificity and AUC of 0.58 (0.47–0.68), 0.79 (0.75–0.82) and 0.79 (0.75–0.82) respectively.ConclusionXpert BC monitor has overall acceptable diagnostic accuracy. Sensitivity is higher for high-grade disease for detecting recurrences in patients with NMIBC on surveillance.