Search Results (96)

Bladder cancer is a common malignancy with high recurrence rates and significant morbidity, necessitating accurate diagnostic and prognostic tools. Although cystoscopy and transurethral resection of bladder tumor (TURBT) remain reference standards, these approaches are invasive and limited by sampling errors and understaging. Consequently, there is growing interest in non-invasive biomarkers, including urine-based assays, blood-based markers, and imaging-derived parameters. Among these biomarkers, multiparametric magnetic resonance imaging (mpMRI), particularly with the Vesical Imaging Reporting and Data System (VI-RADS), has emerged as a robust non-invasive imaging biomarker for local staging and risk stratification. Recent evidence suggests that mpMRI plays a role in predicting treatment response and recurrence, particularly in the context of neoadjuvant therapy. This review provides a comprehensive overview of current non-invasive diagnostic and prognostic biomarkers in bladder cancer, with a particular emphasis on imaging biomarkers. We discuss their clinical utility, limitations, and future integration into multimodal decision-making frameworks. Full article

Background: Surveillance of non-muscle-invasive bladder cancer (NMIBC) relies on cystoscopy and urine cytology, both of which have well-recognised limitations. Molecular urine assays have been developed to reduce the burden of invasive surveillance, yet their real-world clinical utility remains uncertain. Uromonitor^® is a quantitative PCR-based assay targeting hotspot variants in the TERT promoter, FGFR3, and KRAS, which are frequently altered in urothelial carcinoma. We evaluated the performance of Uromonitor^® in routine clinical practice and assessed its technical reproducibility. Methods: Uromonitor^® diagnostic test accuracy was retrospectively calculated from samples from patients undergoing investigation for suspected bladder cancer (n = 64) or surveillance (n = 30) following a prior diagnosis at a tertiary referral centre between 2021 and 2023. Uromonitor^® results were compared with histology where available (n = 49, 52%), or with contemporaneous cystoscopy and urine cytology findings (n = 45, 48%). This pragmatic dual reference standard reflects routine clinical practice but may introduce some heterogeneity in diagnostic accuracy verification. A prospective in-house verification cohort was used to assess inter-laboratory reproducibility. Discordant cases underwent orthogonal next-generation sequencing (NGS) analysis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were calculated for the Uromonitor^® against the standard of care. Results: Ninety-four patients were included in the clinical performance analysis. Overall sensitivity, specificity, PPV, NPV and overall accuracy for Uromonitor^® were 38%, 88%, 63%, 72% and 70%, respectively. Sensitivity was higher in the diagnostic setting (47%; 95% CI 27.3–68.3%) than during surveillance (23%; 95% CI 8.2–50.2%). Several false-negative cases in the verification cohort harboured variants either detectable by NGS at variant allele frequencies below or slightly above the assay’s limit of detection or variants not covered by the assay hotspot design. Inter-laboratory reproducibility was excellent, with 100% concordance observed in the verification cohort. Conclusions: In a real-world clinical setting, Uromonitor^® demonstrated high specificity but limited sensitivity for detection of bladder cancer, particularly during surveillance. A negative result does not reliably exclude recurrence. Assay sensitivity thresholds and restricted variant coverage appear to be key contributors to false-negative results. These findings highlight the need for cautious clinical integration of Uromonitor^®. It is unclear whether this approach has sufficient sensitivity in surveillance to safely reduce cystoscopy frequency. This underscores the need for further refinement of urine-based molecular assays, including a need for enhanced sensitivity and broader mutational coverage before routine clinical adoption. Full article

Introduction: Upper tract urothelial carcinoma is a rare disease with variable prognosis depending on the stage and grade at diagnosis. Current modalities are far from perfect in diagnosis and risk stratification. In this setting, there is an urgent need for diagnostic and prognostic biomarkers to overcome these limitations. Methods: We carried out a narrative review of the literature searching for research articles on diagnostic and prognostic biomarkers for upper tract urothelial carcinoma (UC) and underlined the limitations of current diagnostic modalities. Results: CT urogram (CTU) is the imaging modality of choice in suspected upper tract UC with sensitivity and specificity exceeding 90% but with limitations in smaller lesions. Urine cytology has an excellent specificity for high-grade UC but is limited by low sensitivity leading to a high number of diagnostic ureteroscopies with significant associated risks. Adjuncts such as Fluorescence In Situ Hybridization (FISH) technology and urine DNA methylation markers have shown promising results but need further validation in large cohorts of upper tract UC. Finally, circulation tumour DNA (ctDNA) is a novel approach with great potential in risk stratification and monitoring of minimal residual disease post radical surgery; however, larger prospective studies are required to validate its role similarly to the recent bladder UC trials. Conclusions: There is an urgent need for non-invasive biomarkers that can reliably replace diagnostic ureteroscopies, identify high-risk/invasive disease and select patients for radical surgery or kidney sparing procedures. Full article

Upper tract urothelial carcinoma (UTUC) is a relatively rare malignancy, far less frequent than its counterpart in the bladder, but with a more aggressive course, worse prognosis and unique diagnostic challenges. Despite the histological and molecular similarities between upper and lower tract urothelial tumours, UTUC has many key distinct traits, both clinical and genomic, and must be viewed as a separate entity from bladder urothelial carcinoma (BUC). Ureteroscopy with biopsy is the only means to obtain tissue for histo-logical confirmation of diagnosis and more accurate tumour grading, but is not always feasible or preferable because it carries the risk of potentially severe complications. Aside from the widely available but poorly sensitive urine cytology, a large variety of urine-based diagnostics are increasingly investigated as non-invasive alternatives to ureteroscopy. Fluorescence in situ hybridization (FISH) is the most widely used molecular assay for the diagnosis and monitoring of UTUC, but has failed, as of yet, to display a comparable diagnostic accuracy to the existing gold standards of computed tomography urography (CTU) and ureteroscopy. We herein aimed to comprehensively review all published data on the performance of FISH for the detection of UTUC, in comparison to urine cytology and other assays, while further commenting on the existing challenges and future perspectives in the field of urine-based diagnostics. Across all studies (n = 29) which were included in this review, the sensitivity and specificity of FISH ranged from 36.8% to 100.0% (mean: 75.5%; median: 78.9%) and 34.4% to 100.0% (mean: 84.9%; median: 89.9%), respectively, in the overall patient population, while in the low- versus high-grade subgroups, the sensitivity of FISH ranged from 30.0% to 90.0% (mean: 55.6%; median: 60%) versus 50.0% to 100.0% (mean: 77.9%; median: 78.8%). Furthermore, FISH showed superi-or sensitivity and similar or lower specificity in comparison to cytology, in the over-whelming majority of studies, while Xpert^®BC Detection showed the highest sensitivity values among all evaluated assays, reaching 100% even in the low-grade subgroup, albeit at the cost of a significantly reduced specificity. Despite the adequate overall sensitivity and specificity of FISH, its suboptimal performance in the detection of low-grade UTUC seems to preclude its use as a stand-alone screening test. Full article

Bladder cancer (BCa) is a major global urinary tract malignancy characterized by high incidence, frequent recurrence, and significant mortality. Early diagnosis is crucial for improving prognosis and minimizing invasive procedures; however, current standard techniques, cystoscopy and urine cytology, are limited by invasiveness, cost, low sensitivity, and subjectivity. This has spurred the development of non-invasive diagnostic strategies based on urine analysis. This review highlights five emerging approaches: AI-augmented urine cytology, genomic biomarker assays (e.g., PCR and NGS for mutations and copy-number variations), DNA methylation profiling, RNA biomarkers (mRNA, miRNA, lncRNA), and protein/peptide/metabolite detection utilizing ELISA, SERS, nanozymes, and mass spectrometry. We assess the diagnostic accuracy, innovations, and clinical potential of each, while addressing persisting issues such as lack of standardization, high costs, and insufficient sensitivity for early-stage lesions. Future directions include integrating multi-omics data with AI, advancing point-of-care devices, and conducting large-scale multicenter trials. Together, these developments promise to shift BCa management toward molecular-based early detection, enabling more precise, non-invasive, and personalized patient care. Full article

Background: Urothelial carcinoma (UC) is characterized by high recurrence rates and the need for long-term surveillance. Cystoscopy remains the diagnostic gold standard but is invasive, costly, and burdensome for patients. Urine, as a tumor-proximal and non-invasive biospecimen, represents an attractive source for biomarkers enabling screening, diagnosis, risk stratification, and follow-up. Objective: This review summarizes current and emerging urine-based diagnostic approaches for UC, ranging from conventional cytology to advanced molecular technologies, and discusses their clinical utility, limitations, and future perspectives. Methods: A narrative review of the literature was conducted focusing on urine-based diagnostics for UC, including urinary cytology, FDA-approved and investigational protein and DNA/RNA biomarkers, next-generation sequencing (NGS), cell-free DNA (cfDNA), exosomes, and microRNAs. Evidence from clinical validation studies, meta-analyses, and translational research was evaluated. Results: Urinary cytology remains highly specific for high-grade disease but has limited sensitivity for low-grade tumors. Protein- and DNA-based biomarkers have improved sensitivity but often lack sufficient specificity for standalone use. Recent advances in NGS-based assays enable comprehensive detection of tumor-specific genomic alterations in urinary cfDNA, offering high sensitivity for both initial diagnosis and disease monitoring. Exosomes and microRNAs represent promising biomarkers reflecting tumor biology, though standardization and large-scale validation are ongoing challenges. Overall, multimodal approaches combining cytology with molecular assays appear most promising for clinical implementation. Conclusions: Urine-based diagnostics are rapidly evolving toward integrated liquid biopsy platforms capable of transforming UC management. While several assays show strong potential to reduce reliance on cystoscopy, robust prospective validation, cost-effectiveness analyses, and clinical integration strategies are required before widespread adoption. Full article

Background/Objectives: Haematuria is a common presenting symptom of Urothelial Carcinoma (UC). Traditionally, the “triple workup”—comprising flexible cystoscopy, voided urine cytology and upper tract imaging is used as the standard diagnostic approach for evaluating these patients. However, these investigations can be invasive, time-consuming, and costly. Cxbladder, a urine based genomic biomarker, utilises a non-invasive, singular urine sample to calculate probability of UC based on a patient’s risk factors and gene expression. The aim of Cxbladder is to establish patients with a high probability of no UC being present, which suggests that the traditional investigations are not required. This study evaluates the performance of Cxbladder Triage compared to the standard triple workup in patients presenting with haematuria, excluding a diagnosis of UC. Methods: A prospective, observational study was conducted at a single Australian tertiary hospital. A total of 258 patients, who presented with haematuria from 2020 to 2023, underwent both a Cxbladder Triage test and standard triple workup, comprising three urine cytology samples, imaging and a flexible cystoscopy. Some patients required either a bladder biopsy or tumour resection to further diagnose and treat a suspected UC. Diagnostic accuracy was assessed using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and the proportion of missed tumours. Results: Overall, 5.4% of patients, presenting with haematuria were diagnosed with UC (n = 14). Cxbladder Triage demonstrated a sensitivity of 92.9% (95% confidence interval [CI]: 66.0–99.8) and an NPV of 92.9% (95% CI: 66.0–99.8). This was higher than cytology alone, which recorded a sensitivity of 42.9% (CI 9.9–81.6%) and NPV of 78.9% (95% CI: 54.4–94.0) for the detection of UC. When cytology and imaging were combined to investigate UC, the sensitivity and NPV recorded were 75.0% (95% CI: 42.8–94.5) and 80.0% (95% CI: 51.9–95.8), respectively. The proportion of UC cases missed by Cxbladder Triage was 6.7% (n = 1). Conclusions: In our cohort of patients presenting with haematuria, Cxbladder Triage offers a non-invasive alternative to the traditional workup for the detection of UC, with both a high sensitivity and NPV. Cxbladder Triage offers an alternative diagnostic workup for low-risk patients, which has the potential to reduce unnecessary invasive tests, procedures, and cost to the healthcare system. Full article

Background: Urine cytology remains widely used for surveillance of non-muscle-invasive bladder cancer despite well-known limitations in sensitivity, especially for low-grade tumors. Uromonitor^®, a molecular assay detecting TERT promoter, FGFR3, and KRAS mutations in voided urine, has emerged as a promising adjunct. To evaluate its suitability for routine use, a consolidated assessment of diagnostic performance and a direct comparison with urine cytology are needed. Methods: We conducted a prospectively registered systematic review (PROSPERO CRD420251173244), synthesizing all available studies that evaluated Uromonitor^® for the detection of urothelial carcinoma of the bladder (UCB). Methodological quality was assessed using the QUADAS-2 framework, and certainty of evidence was evaluated following GRADE for diagnostic tests. Sensitivity was prespecified as the primary endpoint. Comparative datasets were identified, and random-effects meta-analyses were performed for sensitivity, specificity, accuracy, and predictive values (PVs). Results: Across eight cohorts evaluating Uromonitor^®, 832 of 3196 patients (26.0%) had histologically confirmed UCB. Aggregated sensitivity was 0.55 (95% CI 0.52–0.58). Specificity was 0.95 (0.94–0.96). Accuracy was 0.85 (0.83–0.86). PPV was 0.79 (0.76–0.82), and NPV was 0.86 (0.84–0.87). Across seven paired datasets, urine cytology demonstrated a sensitivity of 0.42, a specificity of 0.91, an accuracy of 0.78, a PPV of 0.64, and an NPV of 0.81. Pooled odds ratio for sensitivity was 3.16 (0.73–13.76), while diagnostic accuracy yielded 1.71 (1.01–2.90). Differences in specificity and NPV were not statistically significant, whereas the PPV favored Uromonitor^®, reaching statistical significance in pooled analyses. Conclusions: Uromonitor^® demonstrates higher sensitivity and improved accuracy compared with urine cytology, although current performance remains insufficient for stand-alone surveillance. The sensitivity estimate showed very low certainty due to pronounced heterogeneity, underscoring the need for careful interpretation. With advancing DNA recovery methods, incorporation of droplet digital PCR, and rigorous evaluations in prospective multicenter studies, Uromonitor^® may become an integral element of risk-adapted follow-up strategies. Full article

Background: Urine cytology is a highly effective, straightforward, and cost-efficient diagnostic tool for identifying neoplastic and non-neoplastic changes in the bladder, ureter, and renal pelvis. The aim of this study is to demonstrate the high sensitivity and specificity of urine cytology in detecting a wide range of urothelial lesions, including metastatic involvement. Material and Methods: Urine cytology was performed on 9639 cases between 2000 and 2025. The samples, collected from patients, were processed at the Institute of Pathology. Cytological slides were prepared using cytocentrifugation and stained with May–Grünwald–Giemsa (MGG) and Papanicolaou stains. The cytological findings were classified according to WHO, 2004 compared with histological specimens. Additionally, selected cases underwent immunohistochemical and molecular analyses. All samples were anonymized and retrospectively analyzed following the guidelines and regulations of the local ethics committee. Results: Of the total cases, 7051 were classified as benign, 1269 as malignant, and 88 as normal findings. Insufficient material was obtained in 336 cases. No complications were reported during sample collection or processing. The concordance with histological findings for neoplastic lesions was over 96%, with a false-negative rate of 1.84%. The diagnostic methods demonstrated a sensitivity of 90.7% and a specificity of 96.64%. Among the 6956 cases analyzed, 3139 were women (45.13%) and 3817 were men (54.87%). Conclusions: The diagnostic value of urine cytology in representative material is relatively high in assessing both the presence or absence of malignancy and, when applicable, the tumor grade. This large 25-year single-center review demonstrates that urine cytology retains high sensitivity and specificity for the detection of urothelial malignancy, particularly high-grade disease. However, the atypical category remains a major diagnostic challenge and contributes substantially to false-positive results. Full article

Background: Urothelial carcinoma (UC) presents with clinically heterogeneous disease. There is an emerging need to explore the prognosis of non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). Therefore, we aimed to explore the prognostic value of FGFR3 and TP53 mutations and protein expression and to investigate the diagnostic utility of urine cytology and Xpert bladder cancer monitor (BCM) assay in UC. Materials and Methods: A prospective cross-sectional study was conducted in a cohort of 73 Pakistani patients. Cystoscopy, biopsy, tissue diagnosis, UC grade, and stage followed by immunohistochemistry (IHC) and genotyping were recorded. Voided urine samples were also collected for urine cytology and Xpert BCM. Statistical analysis was performed using SPSS version 26.0. A p-value ≤ 0.05 was considered statistically significant. Results: In our selected patients, the majority were males who had smoking history and the common symptom was hematuria. Our findings suggest FGFR3 IHC expression is strongly linked to low-grade NMBIC (p ≤ 0.01). p53 IHC expression supports the findings of the UC grade (p ≤ 0.01). A highly significant association (p < 0.001) was observed between FGFR3 protein expression and underlying mutations. Pro72Arg polymorphism (p = 0.04) was found to be significantly correlated with p53 IHC findings. While comparing cystoscopy with cytology and Xpert BCM, the sensitivity was found to be 85.7% and 58.5%, respectively. Conclusions: The integrated approach of IHC with genotyping could improve risk stratification and guide personalized management strategies. Moreover, as cytology is less sensitive to diagnose UC, especially low-grade tumours, Xpert BCM can be used as a promising diagnostic test for both primary and recurrent BC settings. Full article

Objective: To describe the clinical use of URO17^®, a noninvasive, urine-based immunocytochemistry assay targeting Keratin 17 (K17), as an adjunct to conventional diagnostic methods for urothelial carcinoma. Materials and Methods: These illustrative cases summarize the real-world use of URO17^® in diagnostic workflows for patients presenting with hematuria and those undergoing surveillance for non-muscle invasive bladder cancer (NMIBC). Urine samples were processed via standard immunocytochemistry and interpreted alongside cystoscopic, cytological, and radiographic findings. Discussion: URO17^® was used as a complementary diagnostic tool to help guide clinical management. Negative results supported deferral of invasive procedures in selected patients, while positive findings prompted further evaluation when standard tests were inconclusive. Conclusions: In the seven illustrative cases presented, URO17^® aided clinical decision-making as part of routine diagnostic and surveillance workflows. The test’s integration with existing cytology processes supports its potential role as a noninvasive adjunct for evaluating patients with suspected or recurrent urothelial carcinoma. Full article

Bladder cancer is a prevalent malignancy with high morbidity and mortality, particularly when diagnosed at an advanced stage. Early detection is critical, as it significantly improves prognosis and the patient’s outcomes. Bladder cancer also has a high recurrence rate, necessitating long-term surveillance. While cystoscopy remains the gold standard for diagnosis and monitoring, it is invasive and costly. Urine cytology, though widely used, has high specificity for detecting high-grade urothelial carcinoma but suffers from low sensitivity and limited effectiveness as a stand-alone diagnostic tool. Urinary biomarkers offer a promising, noninvasive alternative for early detection and disease surveillance. This review examines FDA-approved urinary biomarker tests, including NMP 22, UroVysion, and BTA, highlighting their clinical utility and limitations. Additionally, we explore emerging biomarkers such as DNA methylation assays, genomic alterations, and proteomic signatures as well as advanced technologies like next-generation sequencing and machine learning-based platforms. These innovations have the potential to enhance diagnostic accuracy, risk stratification, and recurrent monitoring, ultimately improving early detection and long-term disease management. By evaluating both established and emerging urinary biomarkers, this review aims to provide clinicians and researchers with insights into evolving tools for bladder cancer diagnosis and surveillance. Full article

The BRAF V595E mutation analysis in canine urothelial carcinomas (UCs) has found its way into routine diagnostics, but no data analysis has been published until now. The present study aimed to estimate the distribution of age, sex, and breed in 8365 canine diagnostic samples submitted for BRAF mutation analysis during 2018–2024. The specimens included 8215 urine samples, 17 cytological, and 133 histopathological specimens, and were submitted in cases of suspected UC, to rule out UC, or for screening purposes. All samples were tested for the BRAF V595E mutation using droplet digital PCR (ddPCR). The data were statistically analysed and logistic regression models (Odds Ratio (OR)) were calculated. Compared to samples from mixed-breed dogs, the specimens from Scottish Terriers (OR: 4.21), Shetland Sheepdogs (OR: 2.65), Beagles (OR: 2.33), Fox Terriers (OR: 1.92), Staffordshire Bull Terriers (OR: 1.86), Magyar Vizslas (OR: 1.77), Chihuahuas (OR: 1.70), and West Highland White Terriers (OR: 1.43) had a significantly increased probability of the presence of BRAF mutation indicating UC. The youngest BRAF-positive dogs of these predisposed breeds (n = 4) were 5 years old. In conclusion, screening tests in predisposed breeds may be recommended from the age of 5 years. Full article

Background: Urine microbial analysis is a frequently requested test that is often associated with contamination during specimen collection or storage, which leads to false-positive diagnoses and delayed reporting. In the era of digitalization, machine learning (ML) can serve as a valuable tool to support clinical decision-making. Methods: This study investigates the application of a simple artificial neural network (ANN) to pre-identify negative and contaminated (false-positive) specimens. An ML model was developed using 8181 urine samples, including cytology, dipstick tests, and culture results. The dataset was randomly split 2:1 for training and testing a multilayer perceptron (MLP). Input variables with a normalized importance below 0.2 were excluded. Results: The final model used only microbial and either urine color or urobilinogen pigment analysis as inputs; other physical, chemical, and cellular parameters were omitted. The frequency of positive and negative specimens for bacteria was 6.9% and 89.6%, respectively. Contaminated specimens represented 3.5% of cases and were predominantly misclassified as negative by the MLP. Thus, the negative predictive value (NPV) was 96.5% and the positive predictive value (PPV) was 87.2%, leading to 0.82% of the cultures being unnecessary microbial cultures (UMC). Conclusions: These results suggest that the MLP is reliable for screening out negative specimens but less effective at identifying positive ones. In conclusion, ANN models can effectively support the screening of negative urine samples, detect clinically significant bacteriuria, and potentially reduce unnecessary cultures. Incorporating morphological information data could further improve the accuracy of our model and minimize false negatives. Full article

Urothelial carcinoma (UC) is one of the most frequent tumors in dogs. Besides cytology, histology, and testing for a BRAF mutation, non-invasive biomarkers would benefit the early detection and therapy of UC. This study aimed to compare the detectability of miRNAs in urine sediment and supernatant and to assess their potential as biomarkers for UC. The study involved two phases with 47 canine samples in total; in a pilot trial, ten different miRNAs (miR-16, 21, 103b, 106b, 146, 155, 182, 221, 222, and 375) were isolated from the urine sediments and supernatants from seven healthy control dogs and seven dogs with UC. In a further step, eight miRNAs were isolated from urine sediments from 18 healthy dogs, 11 dogs with purulent cystitis, and 18 dogs with UC. The detectability of miRNAs was improved when isolated from the urine sediment compared with the supernatant. MiR-16 was not deregulated, and miR-106b showed significantly lower expression in cystitis compared with the control. Lower copy numbers were seen for miR-21, 182, 221, and 222 in cystitis cases compared with the controls and UC, respectively. Deregulation was observed for miR-155 and miR-375 between all three groups. A panel including miR-182, 221, 222, 155, and 375 has the potential to discriminate among all three groups in a two-step approach. Full article