Surveillance Of Bladder Cancer Research Articles

Analysis of urine cell-free DNA in bladder cancer diagnosis by emerging bioactive technologies and materials.

Urinary cell-free DNA (UcfDNA) is gaining recognition as an important biomarker for diagnosing bladder cancer. UcfDNA contains tumor derived DNA sequences, making it a viable candidate for non-invasive early detection, diagnosis, and surveillance of bladder cancer. The quantification and qualification of UcfDNA have demonstrated high sensitivity and specificity in the molecular characterization of bladder cancer. However, precise analysis of UcfDNA for clinical bladder cancer diagnosis remains challenging. This review summarizes the history of UcfDNA discovery, its biological properties, and the quantitative and qualitative evaluations of UcfDNA for its clinical significance and utility in bladder cancer patients, emphasizing the critical role of UcfDNA in bladder cancer diagnosis. Emerging bioactive technologies and materials currently offer promising tools for multiple UcfDNA analysis, aiming to achieve more precise and efficient capture of UcfDNA, thereby significantly enhancing diagnostic accuracy. This review also highlights breakthroughs in detection technologies and substrates with the potential to revolutionize bladder cancer diagnosis in clinic.

Introduction of an Advanced Nurse Practitioner (ANP) Led Non-Muscle Invasive Bladder Cancer (NMIBC) Treatment and Surveillance Clinic in Tallaght University Hospital (TUH)

Introduction of an Advanced Nurse Practitioner (ANP) Led Non-Muscle Invasive Bladder Cancer (NMIBC) Treatment and Surveillance Clinic in Tallaght University Hospital (TUH)

Optimizing Z-Stack Plane Selection within Urothelial Clusters in 3D Urine Cytology via AI to Improve Bladder Cancer Screening and Surveillance: Ongoing Multicenter Study

Optimizing Z-Stack Plane Selection within Urothelial Clusters in 3D Urine Cytology via AI to Improve Bladder Cancer Screening and Surveillance: Ongoing Multicenter Study

Optimizing cystoscopy and TURBT: enhanced imaging and artificial intelligence.

Diagnostic cystoscopy in combination with transurethral resection of the bladder tumour are the standard for the diagnosis, surgical treatment and surveillance of bladder cancer. The ability to inspect the bladder in its current form stems from a long chain of advances in imaging science and endoscopy. Despite these advances, bladder cancer recurrence and progression rates remain high after endoscopic resection. This stagnation is a result of the heterogeneity of cancer biology as well as limitations in surgical techniques and tools, as incomplete resection and provider-specific differences affect cancer persistence and early recurrence. An unmet clinical need remains for solutions that can improve tumour delineation and resection. Translational advances in enhanced cystoscopy technologies and artificial intelligence offer promising avenues to overcoming the progress plateau.

Abstract IA020: AI-powered tool for rapid & reliable bladder cancer screening and surveillance: multicenter validation efforts

Abstract Bladder cancer is the most recurrent form of cancer, requiring frequent screening and surveillance, which contributes to its status as the costliest per capita. While urine cytology serves as a crucial adjunct to invasive cystoscopy, it is high volume, labor-intensive, and relatively inconsistent. Despite the implementation of The Paris System, which introduced updated quantitative guidelines, implementation of digital tools for urine cytology still trails the technological advancements seen in semi-automated Pap smear screenings. This lag can be attributed to the diverse cytomorphology of urine specimens and variation in specimen preparation and screening. Our team has developed AutoParis-X (APX), a state-of-the-art technology leveraging deep learning algorithms to extract objective (e.g., nucleus-to-cytoplasm ratio) and subjective (e.g., hyperchromasia) features from whole slide images (WSI). APX transforms these features into the Atypia Burden Score (ABS), offering a quantitative assessment of malignancy and recurrence risks on a scale from 0 to 1. Initially validated with 1300 samples (ThinPrep; Leica Aperio GT450) at Dartmouth Hitchcock, achieving an AUROC of 0.9, APX has evolved into APX-WEB, a user-friendly, web-based tool for cytopathologists. Notable challenges persist, including: 1) validating across nationally representative cohorts with varied specimen preparations and imaging, 2) addressing the intricacies of z-stacking for imaging non-monolayer preparations, and 3) integration of genomics to heighten the sensitivity of imaging assays. This study aimed to establish a performance baseline for APX's adaptability to these challenges without algorithmic adjustments. APX was applied across three distinct cohorts: 1) a preliminary national validation on 500 ThinPrep WSI in collaboration with Hologic; 2) assessment on non-monolayer specimen preparations (e.g., SurePath), using z-stacking, conducted with Johns Hopkins (n=100 WSI); and 3) a pilot study at Dartmouth (n=19) for integrating APX's imaging features with whole exomic sequencing (WES). Preliminary findings indicate: 1) Promising performance on a held-out Hologic national cohort (sensitivity=0.87, specificity=0.73; original APX study: sensitivity=0.88, specificity=0.83). 2) In SurePath z-stack WSI, the number of detected urothelial cells per cluster decreased with distance from the focus plane (rho =-0.13, p<0.001). 3) Of eight cases deemed negative or atypical by cytology, three exhibited TERT mutations, suggesting subclinical recurrence, in contrast to the consistent findings in all nine suspicious or positive cases. This highlights the potential of integrating genomics with image-based classifiers to enhance diagnostic precision. The findings underscore the need for future multicenter work aimed at refining machine learning models to achieve enhanced predictive performance across various operational parameters and settings, facilitating their implementation. Citation Format: Joshua Levy, Keluo Yao, Jonathan Marotti, Darcy Kerr, Edward Gutmann, Sam Harvey, Yoseph Sayegh, Chris VandenBussche, Michael Quick, Peter Costa, Lauren Wainman, Donald Green, Parth Shah, Xiaoying Liu, Louis Vaickus. AI-powered tool for rapid & reliable bladder cancer screening and surveillance: multicenter validation efforts [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr IA020.

Distinct longitudinal patterns of urine tumor DNA in patients undergoing surveillance for bladder cancer.

Cystoscopy is the gold standard for surveillance of non-muscle invasive bladder cancer (NMIBC), but the procedure is invasive and has suboptimal accuracy. The aim of this study was to investigate the potential of analyzing urine samples for the presence of urine tumor DNA (utDNA) to replace cystoscopy for surveillance of bladder cancer recurrence. In this longitudinal, prospective, and observational study, 47 patients were followed for recurrence for 2 years, involving analysis of utDNA using the BladMetrix DNA methylation biomarker test at each cystoscopy. In total, utDNA was detected in 21/23 recurrences (91% sensitivity), including 5/5 T1, T2, and carcinoma in situ (CIS) tumors (100%) and 10/12 Ta tumors (83%), with < 1% false-negative test results. Importantly, utDNA analysis showed the potential to reduce the number of cystoscopies by 55%, benefitting 79% of the patients. Eleven of 23 recurrences (48%) were detected earlier with utDNA than with cystoscopy, and distinct patterns of residual utDNA post-surgery indicated minimal residual disease (MRD) or field effect in 6% and 15% of the patients, respectively. In conclusion, utDNA analysis shows high sensitivity to detect tumor recurrence, potential to reduce the number of cystoscopies, and promise to guide patient-specific surveillance regimens.

Detection of bladder cancer cells using quantitative interferometric label-free imaging flow cytometry.

Bladder cancer is one of the most common cancers with a high recurrence rate. Patients undergo mandatory yearly scrutinies, including cystoscopies, which makes bladder cancer highly distressing and costly. Here, we aim to develop a non-invasive, label-free method for the detection of bladder cancer cells in urine samples, which is based on interferometric imaging flow cytometry. Eight urothelial carcinoma and one normal urothelial cell lines, along with red and white blood cells, imaged quantitatively without staining by an interferometric phase microscopy module while flowing in a microfluidic chip, and classified by two machine-learning algorithms, based on deep-learning semantic segmentation convolutional neural network and extreme gradient boosting. Furthermore, urine samples obtained from bladder-cancer patients and healthy volunteers were imaged, and classified by the system. We achieved accuracy and area under the curve (AUC) of 99% and 97% for the cell lines on both machine-learning algorithms. For the real urine samples, the accuracy and AUC were 96% and 96% for the deep-learning algorithm and 95% and 93% for the gradient-boosting algorithm, respectively. By combining label-free interferometric imaging flow cytometry with high-end classification algorithms, we achieved high-performance differentiation between healthy and malignant cells. The proposed technique has the potential to supplant cystoscopy in the bladder cancer surveillance and diagnosis space.

Active Surveillance in Non-Muscle Invasive Bladder Cancer, the Potential Role of Biomarkers: A Systematic Review.

Bladder cancer (BC) is the tenth most common cause of cancer worldwide and is the thirteenth leading cause of cancer mortality. The non-muscle invasive (NMI) variant represents 75% of cases and has a mortality rate of less than 1%; however, it has a high recurrence rate. The gold standard of management is transurethral resection in the case of new lesions. However, this is associated with significant morbidity and costs, so the reduction of these procedures would contribute to reducing complications, morbidity, and the burden to the health system associated with therapy. In this clinical scenario, strategies such as active surveillance have emerged that propose to manage low-risk BC with follow-up; however, due to the low evidence available, this is a strategy that is underutilized by clinicians. On the other hand, in the era of biomarkers, it is increasingly known how to use them as a tool in BC. Therefore, the aim of this review is to provide to clinical practitioners the evidence available to date on AS and the potential role of biomarkers in this therapeutic strategy in patients with low-grade/risk NMIBC. This is the first review linking use of biomarkers and active surveillance, including 29 articles.

Plasma-Derived Cell-Free DNA as a Biomarker for Early Detection, Prognostication, and Personalized Treatment of Urothelial Carcinoma.

Bladder cancer (BC) is one of the most common malignancies in the United States, with over 80,000 new cases and 16,000 deaths each year. Urothelial carcinoma (UC) is the most common histology and accounts for 90% of cases. BC management is complicated by recurrence rates of over 50% in both muscle-invasive and non-muscle-invasive bladder cancer. As such, the American Urological Association (AUA) recommends that patients undergo close surveillance during and after treatment. This surveillance is in the form of cystoscopy or imaging tests, which can be invasive and costly tests. Considering this, there have been recent pushes to find complements to bladder cancer surveillance. Cell-free DNA (CfDNA), or DNA released from dying cells, and circulating tumor DNA (ctDNA), or mutated DNA released from tumor cells, can be analyzed to detect and characterize the molecular characteristics of tumors. Research has shown promising results for ctDNA use in the BC care realm. A PubMed literature review was performed finding studies discussing cfDNA and ctDNA in BC detection, prognostication, and monitoring for recurrence. Keywords used included bladder cancer, cell-free DNA, circulating tumor DNA, urothelial carcinoma, and liquid biopsy. Studies show that ctDNA can serve as prognostic indicators of both early- and late-stage BC, aid in risk stratification prior to major surgery, assist in detection of disease progression and metastatic relapse, and can assess patients who may respond to immunotherapy. The benefit of ctDNA is not confined to BC, as studies have also suggested its promise as a biomarker for neoadjuvant chemotherapy in upper-tract UC. However, there are some limitations to ctDNA that require improvements in ctDNA-specific detection methods and BC-specific mutations before widespread utilization can be achieved. Further prospective, randomized trials are needed to elucidate the true potential ctDNA has in advancements in BC care.

Patient Satisfaction with a Novel Tele-Cystoscopy Model: Expanding Access to Bladder Cancer Surveillance for Rural Patients.

Tele-cystoscopy involves trained advanced practice providers performing cystoscopy with real-time interpretation by an urologist. The goal of this externally validated care model is to expand the availability of cystoscopy to underserved rural areas. Herein we report on population demographics and describe the socioeconomic benefits of tele-cystoscopy for bladder cancer surveillance. Using an IRB-approved protocol, patients were consented for dual, sequential cystoscopy wherein they experienced a standard-of-care cystoscopy along with tele-cystoscopy. Patients completed a questionnaire that contained both subjective and objective health and socioeconomic-related questions as well as a satisfaction survey. Patients were also probed about factors associated with transportation to their cystoscopy appointments including gasoline costs, travel time, and time off work. Using the Distressed Community Index, patients were ascribed an economic resource category ranging from prosperous to distressed. In total, 48 patients with a mean age of 55 completed surveys after completing dual cystoscopies. Thirteen patients (27%) were uninsured and 10 patients (20%) had Medicaid as primary insurance. The tele-cystoscopy clinic saved patients an average of 235 miles and 434 min of travel time. In total, 82% of patients resided in a distressed community indicating fewer economic resources. Satisfaction results showed a mean score of 31.38 (out of 32). Patients were satisfied with tele-cystoscopy, noting increased access to health care and fewer disruptions impacting bladder cancer surveillance. Tele-cystoscopy may be a viable option to expand access and improve adherence to guidelines for bladder cancer surveillance, particularly benefiting patients in rural areas and those of lower socioeconomic status.

Noninvasive Tests for Bladder Cancer Detection and Surveillance: A Systematic Review of Commercially Available Assays.

An important reason for the high health care costs associated with bladder cancer is the need for frequent cystoscopy for detection and surveillance of this disease. Cytologic analysis of voided urine specimens can assist, but is too inaccurate to replace cystoscopy. In an effort to create reliable, objective, noninvasive mechanisms for detecting bladder cancer, a number of urine-based molecular tests have been developed with the ultimate goal of reducing the frequency of cystoscopy. To summarize the performance of urine-based biomarker tests, currently commercially available in the US, as part of the initial workup for hematuria and for bladder cancer surveillance. In accordance with PRISMA guidelines we performed a systematic review of the literature on the performance of NMP22, BTA, UroVysion, ImmunoCyt/uCyt, CxBladder, and Bladder EpiCheck. Median sensitivity, specificity, negative (NPV) and positive predictive values (PPV) were calculated for each test based on the included studies. Twenty-eight studies met inclusion criteria for the performance of five urine-based biomarker tests in the setting hematuria workup. Median sensitivity ranged from 65.7% -100% and specificity ranged from 62.5% -93.8%. Median NPV ranged from 94.2% -98.3% and PPV ranged from 29% -58.7%. Fourteen studies met inclusion criteria for the performance of six tests in the setting of bladder cancer surveillance. Median sensitivity ranged from 22.6% -92.0% and specificity from 20.5% -97.9%. Median NPV ranged from 52.9% -96.5% and PPV ranged from 48.1% -75.7%. Our analysis finds that while these tests may provide some clinical utility, none of the assays have thus far demonstrated objective evidence to supplant the gold diagnostic standard.

Improving Clinical Wait Times in a Veterans Affairs' Urologic Setting.

Background: Long clinic wait times can contribute to treatment delays and decreased patient satisfaction. Veterans are often waiting in the urology clinic for a prolonged period that delays treatments including possible surgical interventions leading to patient dissatisfaction. Purpose: The purpose of this quality improvement project was to decrease the overall procedural wait times in an outpatient urology clinic by implementing a Fast-Track procedural clinic. Methods: The Fast-Track procedural clinic was developed to expedite care for veterans actively under bladder or prostate cancer surveillance, employing lean methodology principles. We also utilized the Consumer Assessment of Healthcare Providers and Systems Outpatient and Ambulatory Surgery Survey (OAS CAHPS) tool to assess patient satisfaction with the newly implemented Fast-Track clinic. Wait times were collected and analyzed by SPSS statistical software to determine the effectiveness of a Fast-Track clinic. Results: The Fast-Track clinic was implemented to veterans presenting to the urology clinic for procedural appointments from June 2021 to December 2021. The usage of a Fast-Track clinic decreased the overall wait times from 131 to 75 minutes within 8 weeks (43% improvement). The OAS CAHPS tool found that 55% of veterans received easy-to-understand instructions pre-Fast-Track implementation, compared with 59% post-Fast-Track implementation (a 4% improvement). Furthermore, 82% of veterans reported that they did not receive written discharge instructions post-Fast-Track implementation compared with 32% pre-Fast-Track implementation. Conclusion: Incorporating a Fast-Track procedural clinic helped minimize wait times, leading to a reduction in procedural wait times and urologic surgical delays. Implications for Nursing: The implications for practice include future studies focusing on other strategies for improving clinic wait times including block schedules and qualitative measures in the urologic and other specialty areas.

The Value of Negative Urinary Dipstick Tests for Haematuria in Patients Undergoing Surveillance for Low-grade Ta Urothelial Cancer: A Two-stage Prospective Clinical Study in 524 Patients

Background and objectiveThe risk of first recurrence beyond 5 yr for patients with low-grade (LG) Ta non–muscle-invasive bladder cancer (NMIBC) is low enough to consider discontinuing cystoscopic surveillance at that point. However, a positive urinary dipstick test for haematuria (UDH) during and beyond the period of cystoscopic surveillance can disrupt plans to cease surveillance because the association between UDH positivity and recurrence in LG Ta NMIBC is unknown. In a two-stage study, we evaluated this association and explored the role of UDH negativity in predicting the absence of recurrence. MethodsBecause of previously demonstrated changes in recurrence patterns over time, two prospective cohorts were assessed: an “exploratory” cohort (January 2007–March 2008) and a “validation” cohort (November 2017–August 2018). UDH was performed before flexible cystoscopy. Patient, operative, and surveillance data have been recorded prospectively using standard pro forma sheets since 1978 in our institution. Only patients with primary LG Ta pTa NMIBC were included for analysis. Key findings and limitationsWe assessed 231 patients in the exploratory group and 293 in the validation group. The proportion of smokers (67% vs 70%; p = 0.5) and mean follow-up (72.2 vs 79.9 mo; p = 0.2) were similar between the groups. The recurrence rate was higher in the exploratory group (19% vs 11%; p = 0.009), as was the UDH positivity rate (37% vs 11%; p < 0.001). The specificity and negative predictive value were 64% and 83% in the exploratory group, and 90% and 90%, respectively, in the validation group. These values increased further for the subgroup with solitary primary tumours the subgroup without recurrence for 3 yr. Conclusions and clinical implicationsUDH negativity has a high probability of being associated with the absence of recurrence in small LG Ta NMIBC and could be an inexpensive adjunct during surveillance. Ongoing validation, which started in 2019, is being performed in a now-nationalised Scottish protocol in which UDH replaces cystoscopy in years 2 and 4 for patients in the low-risk group. Patient summaryWe investigated the accuracy of a dipstick test for blood in the urine for patients undergoing surveillance for low-grade noninvasive bladder cancer. We found that a negative dipstick test result was highly associated with the absence of tumour recurrence, particularly for patients with the lowest risk. These findings have been introduced into a national protocol designed to reduce the frequency of telescopic inspection of the bladder during surveillance to reduce the burden for patients.

A Molecular Urine Assay to Detect Recurrences During Surveillance of High-Risk Non-Muscle Invasive Bladder Cancer.

High-risk non-muscle invasive bladder cancer (HR-NMIBC) patients require long-term surveillance with cystoscopies, cytology and upper tract imaging. Previously, we developed a genomic urine assay for surveillance of HR-NMIBC patients with high sensitivity and anticipatory value. We aimed to validate the performance of the assay in an unselected prospectively collected cohort of HR-NMIBC patients under surveillance. We included patients from five centers and collected urine sample pairs (evening and morning urines) prior to cystoscopy. Mutation status (FGFR3/TERT) and methylation status (OTX1) was analyzed on DNA from voided urine specimens. A test was considered positive if≥1 alteration was detected in at least one urine sample. The primary endpoint was tumor recurrence. Sensitivity and specificity were determined. A generalized mixed effects model was used to adjust for within-patient correlation. Cox proportional hazard analyses with time-dependent covariates assessed the anticipatory effect of the urine assay. In total, 204 patients and 736 sample pairs were collected. Sixty-three recurrences were diagnosed for which we had concomitant assay results. On cross-sectional analyses, the assay detected 75% (95% CI 62.1% -84.7%) of recurrences, with a specificity of 70% (95% CI 66.4% -73.5%). Furthermore, mixed effects model analyses revealed OTX1 (p = 0.005) and TERT (p = 0.004) as significant predictors for disease recurrence. Median follow-up was 25.3 months (IQR 18.6-30.7). Twenty-nine tumors were diagnosed without concomitant urine samples, which included recurrences detected after urine collection ended. Longitudinal analyses showed that a positive urine assay predicted a recurrence over time (HR 3.5, p < 0.001). Furthermore, a recurrence during the study period was also a predictor for developing future recurrences (HR 2.1, p < 0.001). This study validates the performance of a previously developed urine assay in an unselected cohort of HR-NMIBC patients under surveillance. With a robust sensitivity/specificity and a strong anticipatory effect, this assay proves a useful adjunct ready for evaluation in a future randomized controlled trial.

P257 - Surveillance of Non-Muscle Invasive Bladder Cancer with Blue Light Cystoscopy: A Systematic Review and Meta-Analysis

P257 - Surveillance of Non-Muscle Invasive Bladder Cancer with Blue Light Cystoscopy: A Systematic Review and Meta-Analysis

Urinary Tumor DNA-Based Diagnosis and Surveillance for Nonmuscle-Invasive Bladder Cancer—Current Landscape and Future Directions

Bladder cancer has a significant impact on patients, in terms of both morbidity and financial burden. This is especially true for patients with nonmuscle-invasive bladder cancer, who undergo long-term surveillance via cystoscopy and imaging, resulting in significant costs and risks. To address this issue, urinary tumor DNA analysis, or “urinary liquid biopsy,” has emerged as a potential solution to reduce the testing burden and mitigate many of the costs and risks. Over time, urinary tumor DNA analysis has undergone several refinements. However, existing FDA-approved urinary biomarker assays currently lack the sensitivity and specificity to significantly impact clinical decision-making. Subsequent iterations of these technologies have attempted to bridge this gap by improving their diagnostic accuracy, and ultimately, clinical utility. Here, we discuss the current role as well as future directions of urinary tumor DNA analysis for the detection and long-term surveillance of nonmuscle-invasive bladder cancer.

Cxbladder Monitor testing to reduce cystoscopy frequency in patients with bladder cancer.

Bladder cancer surveillance is associated with high costs and patient burden. CxMonitor (CxM), a home urine test, allows patients to skip their scheduled surveillance cystoscopy if CxM-negative indicating a low probability of cancer presence. We present outcomes from a prospective multi-institutional study of CxM to reduce surveillance frequency during the coronavirus pandemic. Eligible patients due for cystoscopy from March-June 2020 were offered CxM and skipped their scheduled cystoscopy if CxM-negative. CxM-positive patients came for immediate cystoscopy. The primary outcome was safety of CxM-based management, assessed by frequency of skipped cystoscopies and detection of cancer at immediate or next cystoscopy. Patients were surveyed on satisfaction and costs. During the study period, 92 patients received CxM and did not differ in demographics nor history of smoking/radiation between sites. 9 of 24 (37.5%) CxM-positive patients had 1 T0, 2 Ta, 2 Tis, 2 T2, and 1 Upper tract urothelial carcinoma (UTUC) on immediate cystoscopy and subsequent evaluation. 66 CxM-negative patients skipped cystoscopy, and none had findings on follow-up cystoscopy requiring biopsy. Six of these patients did not attend follow-up, 4 elected to undergo additional CxM instead of cystoscopy, 2 stopped surveillance, and 2 died of unrelated causes. CxM-negative and positive patients did not differ in demographics, cancer history, initial tumor grade/stage, AUA risk group, or number of prior recurrences. Median satisfaction (5/5, IQR 4-5) and costs (26/33, 78.8% no out-of-pocket costs) were favorable. CxM safely reduces frequency of surveillance cystoscopy in real-world settings and appears acceptable to patients as an at-home test.

Performance of CellDetect for detection of bladder cancer: Comparison with urine cytology and UroVysion.

To compare the performance of CellDetect, a new biomarker with urine cytology and UroVysiontechnology for bladder cancer detection. We performed an IRB approved prospective, blinded single center study in patients on routine surveillance for nonmuscle invasive bladder cancer and those scheduled for transurethral resection of bladder tumor or radical cystectomy. Patients with bladder catheters, neobladder, ileal conduit, urinary stones, or those with upper tract carcinoma were excluded from the study. Voided urine sample was collected from the participants and each sample was divided into three equal aliquots (CellDetect, Urine cytology and Urovysion). Pathology of the operative specimen was considered the gold standard to which the three markers were compared. The study group included 93 patients with median age was 68 years (range: 34-92 years) with male to female ratio of 12:1. Pathologic evaluation revealed malignancy in 43 cases (46%) of whom 81% had previous history of urothelial bladder cancer. Among all studied markers CellDetect exhibited the best performance followed by urine cytology and U-FISH with diagnostic odds ratio of 4.33, 3.85, and 2.5 respectively. The overall sensitivity, specificity, negative predictive value, and positive predictive value for this test were 84%, 80%, 88%, and 74% respectively. The advantage of this new biomarker was observed both in high grade and low-grade cases. This study demonstrates the advantage of CellDetect as a urine-based assay to detect urothelial bladder cancer over urine cytology and U-FISH test. The high performance was maintained across all cancer grades and stages without compromising the assay specificity. Additional studies are required to test if it can be a noninvasive alternative to cystoscopy.

Clinical performance of Bladder EpiCheck methylation test for active surveillance of non-muscle invasive bladder cancer: Systematic review and meta-analysis.

e16597 Background: Non-muscle invasive bladder cancer (NMIBC) has a favorable 5-year survival, but up to 60% of patients experience cancer recurrence within the first year of diagnosis. The current gold standard for active surveillance is periodic cystoscopy, but this is expensive and invasive. An alternative non-invasive method involves urine cytology, but it has poor sensitivity. Recently developed urine-based molecular diagnostics such as the EpiCheck (Nucleix, Rehovot, Israel) test offers non-invasive and quick testing for active surveillance. In this systematic review and meta-analysis, we aimed to evaluate the diagnostic value of Bladder EpiCheck in active surveillance of NMIBC. Methods: We searched PubMed, Embase, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials for relevant studies published between 1 January 2010 and 31 December 2022. The primary outcome was the sensitivity / negative predictive value (NPV) and specificity (PPV) of Bladder EpiCheck in active surveillance of NMIBC. We also performed a subgroup analysis to evaluate the performance of EpiCheck in detecting the recurrence of high-grade and low-grade NMIBC. Results: Our systematic search identified 110 articles, from which 6 studies were included in the final analysis. Compared with urine cytology, EpiCheck had a higher pooled sensitivity (73% [95% CI: 59-83] vs. 51% [95% CI: 30-72]) and NPV (90% [95% CI: 79.5-95.2] vs. 84% [95 % CI: 69-92]. However, EpiCheck had a lower pooled specificity (63% [95% CI: 48-76] vs. 97% [95% CI: 89-99]) and PPV (63% [95% CI: 48-76] vs. 85% [95 % CI: 69-94] than urine cytology. Similarly in subgroup analysis, EpiCheck had a higher pooled sensitivity than urine cytology in detecting both high-grade (86% [95% CI: 78-91] vs. 63% [95% CI: 43-80]) and low-grade (44% [95% CI: 34-55] vs. 13% [95% CI: 7-23]) NMIBC. Conclusions: The Bladder EpiCheck test has a better sensitivity than urine cytology and may be utilized as a part of the active surveillance strategy for NIMBC recurrence.

CarePoint assay in the management of bladder cancer: A pilot study.

e16593 Background: Bladder cancer afflicts over 700,000 patients in the US and is one of the most expensive cancers to treat. Given a recurrence rate of up to 70%, regular often prolonged surveillance is required. In addition to urine based tests, current standard evaluation includes cystoscopy which is burdensome for patients and physicians; there has long been a need for a reliable non-invasive alternative diagnostic tool. While there is a wealth of literature on urinary biomarkers, no single biomarker has demonstrated consistent high sensitivity and specificity. Methods: The CarePoint Assay, a point-of-care (POC) tool, can perform multiple biomarker tests simultaneously. In this study, urine was collected from patients undergoing urologic evaluation for hematuria from three separate institutions. The urine was sent for central evaluation and the CarePoint Assay was used to detect the bladder cancer biomarker BTA. POC results were then compared to results from a highly sensitive 6-hour ELISA. The accuracy of distinguishing high-grade tumors, low-grade tumors and no tumor present were compared between the two methods. Results: The CarePoint Assay demonstrated excellent correlation with the ELISA in detecting biomarker levels and distinguishing high-grade tumors as well as a superior specificity (88% versus 77%) for ELISA, sensitivity (52% vs. 72%) for ELISA and a limit of detection of 2.55 ng/mL (16 picomolar). Conclusions: With this high performance, the CarePoint Assay has the ability to detect and multiplex multiple other bladder cancer biomarkers with higher sensitivity and specificity. Additional biomarker analysis using the CarePoint Assay may yield the medically desired higher levels of sensitivity and specificity for a non-invasive point-of-care bladder cancer test, ultimately limiting the patient burden of bladder cancer surveillance.