White Light Cystoscopy Research Articles

Phase II multi-center trial of optical coherence tomography as an adjunct to white light cystoscopy for intravesical real time imaging and staging of bladder cancer

BackgroundOptical coherence tomography (OCT) is a novel imaging modality that provides microstructural information of different tissue layers using near-infrared light. This prospective, multicenter phase II trial aimed to assess the accuracy of OCT-assisted cystoscopy for bladder tumor staging. MethodsPatients with primary or recurrent bladder tumors (Ta,T1) identified by outpatient cystoscopy were included. The primary objective was to assess the accuracy and positive predictive value of for determining tumor stage ≥T1 correlated by histopathology. 72 suspicious lesions from 63 patients were eligible to analyze in the study. All suspected lesions were evaluated with conventional cystoscopy, interpreted in real-time using OCT, and then resected. All results were compared to pathology. A total of 363 OCT images of tumor and normal mucosa in 25 patients were obtained to evaluate diagnostic efficacy of the computer-aided texture analysis algorithm. ResultsSensitivity and specificity for predicting invasive tumors (≥ T1, n = 17) were 58.8% and 92.7% for cystoscopy, 64.7% and 100% for OCT-assisted cystoscopy, respectively. Accuracy of cystoscopy and OCT-assisted cystoscopy for predicting invasive tumor was 84.7% and 91.7% (P = 0.063), respectively. Cystoscopy and OCT-assisted cystoscopy correctly predicted T stage in 52/72 and 59/72 cases, respectively (P = 0.016). Cystoscopy missed 2 more invasive tumors than OCT-assisted cystoscopy. Cystoscopy (14.3%, 1/7) and OCT-assisted cystoscopy (28.6%, 2/7) showed relatively low sensitivity in detecting muscle invasion. Computer aided texture analysis demonstrated 75.1% sensitivity, 64.0% specificity, and 74.4% accuracy for differentiating tumor and normal urothelium. ConclusionOCT-assisted cystoscopy is a real time noninvasive and simple procedure that enhanced the accuracy of staging bladder tumors and prediction of any tumor invasion. Though the study did not meet the prespecified primary endpoint, OCT imaging is a promising adjunct to cystoscopy that may supplement intraoperative decision-making during transurethral resection of bladder tumors and additional prospective studies are warranted.

Narrow band imaging versus white light cystoscopy alone for transurethral resection of non-muscle invasive bladder cancer

Narrow band imaging versus white light cystoscopy alone for transurethral resection of non-muscle invasive bladder cancer

REVIEW OF DIAGNOSTIC OPPORTUNITIES FOR IMPROVEMENT OF DETECTION OF NON-MUSCLE INVASIVE BLADDER CANCER

Recently white light cystoscopy (WLC) is the standard method for detection of urothelial cell carcinoma of the bladder. Regarding the problem that on the one hand the sensitivity of WLC is not high enough, and on the other hand it can miss small ‘satellite’ tumors or carcinoma in situ (CIS), other techniques are used. Such techniques are the new imaging by photodynamic diagnosis (PDD) and narrow band imaging (NBI). The both techniques allow very accurate bladder cancer visualization. It is obviously very important to improve diagnostic accuracy and as consequence it increases the quality of resection. Regarding the meta-analysis of several studies, it can be concluded that the new imaging techniques should be applied for a more precise diagnostic, comparing with WLC. Further results of multicentric meta-analysis between these two techniques will stabilize their advantages for concrete clinical indications.

Initial Results of First In Vivo Imaging of Bladder Lesions Using a High-Resolution Confocal Microendoscope.

Purpose: Conventional cystoscopy plays an important role in detection of bladder cancer; however, it is difficult to differentiate benign and neoplastic lesions based on cystoscopic appearance alone. Advanced microscopic modalities, such as confocal laser endomicroscopy and optical coherence tomography, have been shown to provide critical histopathologic information to help identify neoplastic bladder lesions in real time, but their availability and clinical adoption are limited due to a high cost. In this study, we present the first use of a novel and low-cost ($ <5000) confocal high-resolution microendoscope (confocal HRME) for in vivo imaging of bladder lesions. Materials and Methods: In a cohort of 15 patients undergoing white light cystoscopy as part of their standard of care, high-resolution images of proflavine-stained bladder lesions were acquired in vivo using the confocal HRME. Based on these images, we evaluated the ability of the confocal HRME to visualize uroepithelium with subcellular resolution and high contrast. Furthermore, we analyzed the cellular architecture and staining patterns of benign and neoplastic bladder lesions in confocal HRME images and compared results to that of standard cystoscopy and histopathology. Results:In vivo imaging in the pilot study demonstrates that the confocal HRME resolved subcellular structures of bladder uroepithelium with high contrast. In a wide range of clinical conditions from normal bladder wall to benign and neoplastic lesions, confocal HRME images revealed important diagnostic features that correlated to histopathology. Conclusions: The confocal HRME provides an affordable, portable, and easy-to-use tool to allow real-time and high-contrast subcellular characterization of bladder lesions, well suited for bladder cancer detection in community and resource-constrained settings. The ClinicalTrials.gov Identifier: NCT02340650.

Blue light cystoscopy for detection of invasive bladder tumor: Results from multi-institutional registry

The role of blue light cystoscopy in increasing detection and decreasing recurrence and possibly progression rates in non-muscle invasive bladder cancer compared to white light cystoscopy is well supported in the literature. Here we evaluated the role of blue light cystoscopy in detecting invasive tumors that were not visible on white light cystoscopy. Using the multi-institutional Cysview registry database, patients who had at least one white light negative/blue light positive lesion with invasive pathology (≥T1) as highest stage tumor were identified. All white light negative/blue light positive lesions and all invasive tumors in the database were used as denominators. Relevant baseline and outcome data were collected. A total of 3514 lesions from 1257 unique patients were evaluated. Of all the lesions in the database, 818 (23.2%) lesions were white light negative/blue light positive of which, 7% (55 lesions from 47 unique patients) were invasive. When all the invasive lesions in the database were considered (total of 494 lesions), 11% were white light negative/blue light positive. Of patients with complete follow up in the database (32), 22 (68%) patients underwent radical cystectomy and 11/22 (50%) showed pathologic upstaging including 4/22 (18%) patients with node positive disease. A considerable proportion of invasive lesions are only detectable by blue light cystoscopy and rate of pathologic upstaging is significant. Our findings suggest an additional benefit of blue light cystoscopy in detection of invasive bladder tumors that has implications for treatment approach.

Preoperative predictive factors of carcinoma in situ in the normal-appearing mucosa in patients who underwent an initial transurethral resection for non-muscle-invasive bladder cancer under white light cystoscopy.

BackgroundAlthough few studies evaluated the significance of random biopsies under white light cystoscopy (WLC) in patients with non‐muscle‐invasive bladder cancer (NMIBC), the findings are controversial.AimThis aim of this study was to evaluate what kind of preoperative covariates were useful as predictive factors in detecting carcinoma in situ (CIS) from normal‐appearing mucosa using random bladder biopsies under WLC.Methods and ResultsA total of 229 patients with NMIBC underwent initial TUR followed by random biopsies under WLC at Red Cross Takayama Hospital between 2007 and 2016. These patients underwent TUR with complete resection of intravesical visible tumors followed by random biopsies of normal‐appearing mucosa. In this study, random bladder biopsies of normal‐appearing urothelial mucosa, excluding abnormal mucosa, were carried out with a cold punch in the selected intravesical sites. The covariates included age, gender, the urine cytology result, presence of an abnormal mucosa, number of tumors, size of the largest tumors, configuration of the tumor, and tumor type. Abnormal mucosa was defined as reddish or mossy areas at the time of TUR under WLC. The primary endpoint was to determine what kind of preoperative covariates were useful as predictive factors in detecting CIS from normal‐appearing mucosa using random bladder biopsies under WLC. Finally, 212 patients were evaluated, and 67 patients (31.6%) were diagnosed with CIS from normal‐appearing mucosa. In univariate analysis, positive urine cytology, abnormal mucosa, and the number of tumors were significantly associated with concomitant CIS. On multivariate analysis, positive urine cytology and abnormal mucosa were significantly associated with CIS.ConclusionThe patients who were diagnosed with positive urine cytology or abnormal mucosa by WLC are ideal candidates for TUR followed by random biopsy of normal‐appearing mucosa.

Raman Spectroscopy to Characterize Bladder Tissue for Multidimensional Diagnostics of Cancer in Urology

Abstract Fiber optic Raman spectroscopy offers labelfree identification of cancer in the bladder under in vivo conditions. However, state-of-the-art Raman technology does not enable to scan the entire bladder wall. Our multidimensional approach within the project Uro-MDD combines panoramic 3D-image reconstruction of white light cystoscopy and fluorescence lifetime imaging to define regions of interest for Raman-assisted diagnostics. First Raman results are presented from human control and cancer bladder specimens that demonstrated how to obtain specific molecular information. Such Raman images can be used in a clinical setting to determine cancer margins and the resection status. Fiber probes are under development to translate the technique to in vivo screening.

First results of computer-enhanced optical diagnosis of bladder cancer

Abstract Bladder cancer is the sixth leading cancer cause worldwide. Non-muscle invasive tumors can be diagnosed and treated endoscopically. Based on biopsies alone, pathologists cannot determine the spatial organization of specimens, their relationship with each other, or their complete removal. To extend white light cystoscopy as the gold standard for bladder cancer detection, diagnosis and removal of small or flat lesions, new image-based technologies have been investigated. These include a stereo-cystoscope for improved orientation and navigation, computation of 2D and 3D panoramic images for extended visualization and documentation, as well as label-free fiber-based fluorescence-lifetime imaging (FLIM) and Raman-spectroscopy in combination with statistical data analysis. Combining all these technologies, cystoscopy can will be further enhanced to include new diagnostic possibilities.

The combination cytology/epichek test in non muscle invasive bladder carcinoma follow-up: Effective tool or useless expence?

ObjectiveTo identify in which cases after cytological diagnosis, the Bladder EpiCheck test could represent an effective tool in non-muscle invasive bladder carcinoma or an useless expence. Materials and methods375 patients diagnosed with non-muscle invasive bladder cancer, 269 with high grade urothelial carcinoma and 106 with carcinoma in situ, were treated and followed for 1 year. The treatment was an intravesical instillation of Bacillus Calmette-Guerin in 305 patients and Mitomycin-C in 70 patients.During the follow-up patients were evaluated by voided urine cytology and white-light cystoscopy, according to the European Association of Urology Guidelines. Bladder EpiCheck test was performed together with cytology in all cases. ResultsAnalyzing Bladder Epicheck results for each category defined by the Paris System for Reporting Urinary Cytology, we found that the Episcore >60 correlates with histological diagnosis of high grade urothelial carcinoma (HGUC) in atypical urothelial cells and Suspicious for High Grade Urothelial Carcinoma (P = 0.0002 Odds Ratio 0.05926 95% Confidence Interval from 0.01127 to 0.3116 and P = 0.0009 Odds Ratio 0.0315595% Confidence Interval from 0.001683 to 0.5914, Fisher's exact test, respectively), while in Negative for high grade urothelial carcinoma and HGUC patients Episcore is not helpful to identify cases with histological diagnosis of HGUC (P = 0.101 and P = 0.58 Fisher's exact test, respectively). Considering an Episcore ≥ 90 in the HGUC cytological group, this seems not to be correlated with a histological diagnosis of HGUC (P = 0.090 Fisher's exact test). ConclusionsCytology and Bladder EpiCheck test in combination may have the potential to reduce cystoscopies in the follow-up of non-muscle invasive bladder cancer only for cytological diagnoses of atypical urothelial cells and Suspicious for High Grade Urothelial Carcinoma . Moreover, in patients with a cytological diagnosis of Negative for high grade urothelial carcinoma or HGUC, cytology alone seems to be safe and cost-effective.

Prospective evaluation of blue-light flexible cystoscopy with hexaminolevulinate in non-muscle-invasive bladder cancer.

To evaluate the utility of blue-light flexible cystoscopy (BLFC) for surveillance of non-muscle-invasive bladder cancer (NMIBC). Prospective cohort of consecutive patients who underwent office-based BLFC for NMIBC. Clinical information was collected including cystoscopic findings and pathological data. A total of 322 cases were performed on 190 patients. The mean age was 71years and 83% were men. The highest stage prior to BLFC was Ta, carcinoma in situ (CIS), T1, and T2 in 45.3%, 18.4%, 30% and 2%, respectively. Prior to BLFC, 16.8%, 60.5%, and 16.8% were low grade (LG), high grade (HG), and CIS, respectively. Intravesical bacille Calmette-Guérin and intravesical chemotherapy were used in 54.2% and 18.4%, respectively. White-light cystoscopy (WLC) and BLFC were both normal in 173 (53.7%) of cases. WLC was normal and BLFC was abnormal in 26 (8%) cases. Of these, 15 had office-based biopsy and cancer was detected in 13 (87%; six CIS, four HG Ta, three LG Ta). Both WLC and BLFC were positive in 83 (25.8%) cases and 33% had additional tumours found. Cancer was found in 27 (75%) of WLC+/BLFC+ who underwent office-based biopsy including 19 LG Ta, six HG Ta, and two CIS. Incorporation of BLFC in clinical practice has potential advantages of finding cancer in cases with normal WLC. BLFC detected additional cancers in 33% of patients with positive WLC and BLFC, which can improve surveillance and performance of office-based biopsy. Further research is needed to determine cost-effectiveness and impact on recurrence rates.

Abstract IA07: Potential benefits of and obstacles to use of urine-based tumor markers

Abstract There are many potential uses of urine-based tumor markers in improving detection and surveillance of bladder cancer. Prior to incorporation of urine markers into clinical care, it is important to demonstrate improved efficacy over standard clinical tools. The main areas where urine markers may improve care is in triaging patients with hematuria who need evaluation, reducing frequency of cystoscopy in patients with low-grade disease, improving detection of high-grade patients, and improving prediction of outcomes in patients with bladder cancer. There are currently limitations in white light cystoscopy, especially in detection of carcinoma in situ (CIS). Also, the most widely used urine marker, cytology, has low sensitivity for detecting low-grade cancer and can miss up to 40% of high-grade bladder cancer. Most urine markers have improved sensitivity over urine cytology but reduced specificity. The prevalence of disease impacts the positive and negative predictive values of these tests. For hematuria, the prevalence of cancer is very low in microhematuria patients; as such, the positive predictive value of urine markers is low. Clinicians need markers to provide clinically useful information by either having a high positive predictive value or high negative predictive value (NPV). In the context of microhematuria, many patients are not adequately evaluated and this can result in delays in diagnosis. A urine marker with a high NPV could reduce need for cystoscopy for low-risk patients and enrich the cohort of patients more likely to have cancer. For surveillance, the sensitivity of urine markers has not been sufficient to replace cystoscopy. It is possible that replacing some cystoscopy procedures by alternating a marker with cystoscopy for patients with low-grade disease may be possible, but trials are needed to demonstrate the safety and efficacy of this approach. In high-grade patients, there is need for improved detection of recurrent tumors, especially CIS, since white light cystoscopy has been shown to miss tumors compared to enhanced cystoscopy. A high-performing urine marker could improve detection, but appropriate studies need to be performed to demonstrate sufficient PPV to justify modifying clinical care. There is also a potential role for using markers to improve management of patients with atypical cytology or cystoscopic findings. They could also improve prediction of outcomes in patients with high-grade disease, especially in those patients treated with intravesical therapies. In order for urine markers to be incorporated into guidelines, it is important to develop appropriate trials to validate their utility. There is also a need to consider overall cost of care and patient perspectives. Citation Format: Yair Lotan. Potential benefits of and obstacles to use of urine-based tumor markers [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr IA07.

Methylation study of the Paris system for reporting urinary (TPS) categories

AimsBladder EpiCheck is one of several urinary tests studied to identify bladder tumours and analyses 15 methylation biomarkers determining bladder cancer presence on the basis of methylation profile.Methods374 patients diagnosed...

Shedding Light on Bladder Cancer Diagnosis in Urine.

Blue light cystoscopy (BLC) is the most recent clinical approach in the detection and diagnosis of bladder cancer, a common type of cancer with a high rate of recurrence. Representing a significant advance over previous approaches, this photodynamic diagnostic technique uses a photosensitiser prodrug as an adjunct to white light cystoscopy to enhance the in vivo detection of malignant tissues in the bladder based on their distinctive fluorescence. Whilst it does improve detection rates, BLC remains an invasive and costly procedure. Meanwhile, a variety of noninvasive urine detection methods and related microdevices have been developed, none of which have yet entered routine clinical use due to unsatisfactory sensitivity. Following a brief description of the current approaches and their limitations, we provide here a systematic review of a newer niche research aiming to develop a noninvasive adaptation of photodynamic diagnosis. The research to date surrounding the ex situ use of photosensitiser prodrugs for urinary diagnosis of bladder cancer is also discussed.

Preclinical and Clinical Evaluation of a Novel, Variable-View, Rigid Endoscope for Female Cystoscopy

OBJECTIVETo evaluate the preclinical and clinical performance of the pivoting lens rigid Endocameleon (ECAM) endoscope in white light cystoscopy (WLC). MATERIALS AND METHODSPreclinical evaluation was performed ex vivo in CT-based, anatomically accurate and validated bladder phantoms. Six defined tasks with objective endpoints were compared between ECAM-WLC and rigid WLC (30° view angle, rWLC) in 30 interventions. Subsequently, the comparison was transferred to in vivo n = 21 interventions. A validated usability score (System Usability Scale, SUS) as well as physician and patient-related outcomes were assessed using Likert-scale-based questionnaires. Intra- and postinterventional complications were recorded according to the Clavien-Dindo classification. RESULTSThe ex vivo evaluation showed a significant superiority of ECAM-WLC in 4 of 6 endoscopic tasks. Noteworthy is the lower pressure on the bladder neck due to the endoscopesalteration of the endoscope (4/60 vs 17/60, P <.0001) and a more precise imaging of all bladder regions (22/30 vs 30/30, P = .046), including the anterior wall (0/30 vs 28/30, P <.0001). In vivo, surgeons rated the ECAM-WLC with an “excellent” SUS of 86.79%, also expressing that ECAM-WLC would enhance bladder surface visualization (4.52/5.0 ± 0.51), with a preferred use for ECAM-WLC during their next cystoscopy (4.62 ± 0.50). Patients reported ECAM-WLC to be less painful (4.5/5.0 ± 0.84) compared to rWLC. No intervention-related complications were observed. CONCLUSIONECAM-WLC is a safe and accessible procedure that could improve conventional diagnostic WLC by combination of the advantages of fWLC and rWLC.

Carcinoma in situ of the bladder: why is it underdetected?

The standard diagnosis of carcinoma in situ (CIS) of the bladder, based on white light cystoscopy and urine cytology, is limited because CIS can vary from normal-appearing mucosa to a lesion indistinguishable from an inflammatory process. Intravesical instillation of Bacillus Calmette-Guerin (BCG) remains first-line therapy; however, a significant proportion of cases persist or recur after BCG treatment. This review summarizes recent improvements in the detection and treatment of CIS. The new optical technologies improve CIS detection, with a potential positive impact on oncological outcomes. The usefulness of MRI-photodynamic diagnosis fusion transurethral resection in CIS detection is unclear and further studies are needed. BCG instillation remains the first-line therapy in CIS patients and seems to improve recurrence and progression rates, especially with the use of maintenance. Intravesical device-assisted therapies could be effective in both BCG-naïve and BCG-unresponsive CIS patients, but further studies are ongoing to clarify their clinical benefit. A phase II clinical trial with pembrolizumab has shown the potential effectiveness of immune checkpoint inhibitors in BCG-unresponsive CIS patients and further trials are ongoing. New optical techniques increase the CIS detection rate. BCG instillation remains the first-line treatment. Immune checkpoint inhibitors could be a future alternative in BCG-naïve and BCG-unresponsive CIS patients.

Blue Light Cystoscopy: Indications and Outcomes.

It has been firmly established that hexaminolevulinate-assisted blue light cystoscopy (HAL-BLC) reduces cancer recurrence rates. This review explores the impact of HAL-BLC on other meaningful outcomes in patients with bladder cancer, including disease progression, and earlier detection of disease at the time of surveillance cystoscopy. A randomized clinical trial confirmed earlier implementation of HAL-BLC at the time of surveillance cystoscopy increased identification of cancerous lesions, including those of high grade, when compared with white light cystoscopy. In addition, the evidence is evolving that the use of HAL-BLC at the time of endoscopic treatment of high-risk tumors may lead to lower rates of progression to muscle invasion, and this in part may be due to better risk stratification leading to changes in treatment plan. The clinical contexts for the use of HAL-BLC are broader than prior knowledge. It is also becoming more clear that the positive impact of HAL-BLC is likely more than just reducing cancer recurrence rates, and patients would benefit from the technology at many time points in the management and follow-up of their disease.

V12-01 REAL-TIME AUGMENTED BLADDER TUMOR DETECTION WITH DEEP LEARNING

INTRODUCTION AND OBJECTIVE:White light cystoscopy is the standard imaging modality for bladder cancer detection, treatment and surveillance, but around 15% of tumors are missed. Enhanced cystoscopy...

Current Standards in the Endoscopic Management of Bladder Cancer: A Survey Evaluation among Urologists in German-Speaking Countries

Introduction: To assess the current diagnostic, treatment, and documentation strategies for bladder cancer (BC) in German-speaking countries. Materials and Methods: A 14-item web-based survey was distributed among members of the German, Austrian, and Swiss Associations of Urology, addressing physicians who perform cystoscopies and transurethral resection of bladder tumors (TURB). Results: The survey was responded to by 308 of 5,564 urologists with a mean age of 49.5 years (response rate: 5.5%). The majority of participants (57.3%) practice in an outpatient setting. White light cystoscopy only is used by 60.2%, with additional photodynamic diagnosis and narrow band imaging by 36.8 and 12.5%, respectively. Endoscopic findings are documented in written form by 93.5%, followed by image capture (33.7%) and a central data archive (20.8%). Inpatient hospital urologists document cystoscopic findings by freehand drawing (21.4 vs. 11.4%, p = 0.017), and with a fixed bladder scheme (31.3 vs. 7.4%, <0.05) significantly more frequently. Cystoscopic findings are mainly conveyed to other health professionals in written form (77.4%), and significantly more often by inpatient urologists (p < 0.05). Conclusions: Significant differences exist in the approach to documenting and communicating cystoscopic BC findings. Accurate graphic documentation of lesions, visualization of the mucosa’s totality, and meticulous consultation of previous surgical reports require improvements to reduce recurrence and progression rates.

Detecting Invisible Bladder Cancers With Blue Light Cystoscopy

A 90-year old man with no significant past medical history presented to urology clinic complaining of gross hematuria, urinary frequency, and dysuria. Previous urine cytology was atypical but 2 white-light cystoscopies failed to show any lesions. The patient was taken for intraoperative blue light cystoscopy, which revealed multiple lesions that were then resected. Pathology revealed high grade urothelial carcinoma with lamina propria invasion and the patient was managed successfully with Bacille Calmette Guerin therapy. This case highlights an important role for blue light cystoscopy in diagnosing patients with high suspicion for malignancy but negative white light cystoscopy.

Diagnostic Performance of Novel Urine-Based mRNA Tests (Xpert and Urinary Metabolomics Markers Assay) for Bladder Cancer Detection in Patients with Hematuria

BACKGROUND: Hematuria is the most frequent presenting symptom in the vast majority of bladder cancer (BC) patients. The current recommended evaluation of hematuria includes cross sectional imaging and cystoscopy with possible high negative results, expensive costs and substantial patient burden. OBJECTIVES: To validate novel urine-based mRNA-dependant tests; Xpert test and urinary metabolomics assay (CRAT and SLC 25A20genes expression) for BC detection in patients with hematuria. METHODS: Patients presented with hematuria to our tertiary care hospital were evaluated by CT urogram and office white light cystoscopy with subsequent inpatient biopsy for positive findings. Voided precystoscopy urine samples were prospectively collected. Xpert test, assay of targeted urinary metabolomics and cytology, were performed. The tests characteristics presumably were calculated based on the ability to identify BC noninvasively. RESULTS: Between March 2018 and June 2019, 181 patients were included in the final analysis with mean (±SD) age 62 (±10) years with 168 (92.8%) males. Macroscopic hematuria was encountered in 153 (84.5%) patients with irritative bladder symptoms in 48 (26.5%) patients. BC was confirmed by cystoscopy/biopsy in 36 (19.9%) patients. The performance characteristics of Xpert alone (SN: 73%, SP: 83%, NPV: 92%, PPV: 52%) (AUC 0.84, 95% CI 0.75–0.93, p = 0.001), metabolomics assay alone (SN: 89%, SP: 93%, NPV: 97%, PPV: 78%) (AUC 0.91, 95% CI 0.85–0.98, p &lt; 0.001) and combination of both test results (SN: 66%, SP: 98%, NPV: 92%, PPV: 97%) (AUC 0.83, 95% CI 0.74–0.93, p = 0.001) were notably superior to urine cytology (SN: 30%, SP: 84%, NPV: 83%, PPV: 33%) (AUC 0.58, 95% CI 0.47–0.69, p = 0.154) for BC prediction. Cystoscopy-negative patients (CNP) were followed-up for a median (range) 12 (2–19) months. Re-cystoscopy was done for 35 patients with persistent symptoms. BC was diagnosed in 6 patients. Xpert and urinary metabolomics results were observably positive in those 6 patients. CONCLUSION: Xpert test and assay of urinary metabolomics (CRAT and SLC 25A20 genes expression) have the potential for BC detection in hematuria patients. These non invasive urine based tests can help prioritization of the use of invasive diagnostic tests in systems with long waiting times.