TEST:

Bladder EpiCheck®

"In 316 patients undergoing surveillance from July 2023 until August 2024, 38 cancers were detected, of which 29 were high-grade and 13 were carcinoma in situ (CIS), an aggressive form of bladder cancer often missed by white light cystoscopy, that can progress to muscle-invasive cancer if left untreated. White light cystoscopy detected 17 (59%) of the high-grade cases and 4 (31%) of the CIS cases versus 28 (97%) and 12 (92%), respectively, detected by Bladder EpiCheck and confirmed by photodynamic diagnosis (PDD) biopsies. Specificity was 97% (261/270) for cystoscopy and 94% (253/270) for Bladder EpiCheck. Additionally, Bladder EpiCheck was able to detect 65% more high-grade disease recurrences compared to white light cystoscopy (28 vs. 17), by performing biopsy under PDD in patients with a negative white light cystoscopy and a positive Bladder EpiCheck result. Nine of the 16 (56%) patients that were missed by white light cystoscopy but detected with Bladder EpiCheck and PDD had CIS."

P=N/A, N=100, Recruiting, Regina Elena Cancer Institute

The BE post-BCG status and variations in EpiScore values can help us identify patients at higher risk of any bladder cancer event and BCG failure promptly. These data can have an impact on disease management.

The consistently strong performance of BE indicate that a positive test could improve timely disease recurrence detection and a negative test could rule-out HG disease. Furthermore, the low rate of false positive results, potentially minimizes unnecessary downstream procedures and patient anxiety.

Bladder EpiCheck® is an effective diagnostic tool in UTUC, showing a promising diagnostic accuracy, with a Se and NPV of 85% and 84%, respectively. Its use in UTUC diagnosis and follow-up could reduce or postpone the need for more invasive procedures, such as URS, thereby reducing the procedure-associated risks and improving patients' quality of life. Although further research and large prospective studies are needed, the current results indicate that Bladder EpiCheck® is a promising tool in UTUC diagnosis, treatment decision-making, and follow-up.

P=N/A, N=600, Not yet recruiting, Nucleix Ltd.

BE may be useful in detecting residual tumor before second TUR and benefit in clinical decision making with high specificity and negative predictive value. These results encourage the use of BE to reduce number of unnecessary second TUR procedures. It may improve cost effectivity and quality of life as high numbered studies are needed to support these views and to incorporate BE into clinical practice.

Conclusions BE could allow a reduction in the number of cystoscopies in the follow-up of HR-NMIBC, with a potential improvement in the quality of life of patients, given its high NPV. Management of a positive BE must be individualized for each patient, with a high Se for non-LG recurrence in HR-NMIBC patient.

The combination of BE and urinary cytology correctly identified 29 out of 30 carcinomas, while 289 were correctly diagnosed as negative results. The combination of BE and cytology could be the most effective approach for follow-up diagnosis in patients with high-grade NMIBC, reducing unnecessary invasive procedures.

Conclusions Bladder EpiCheck, though outperformed at times, remains preferred for NMIBC surveillance due to its broader study base and larger sample sizes, enhancing reliability. A DTA meta-analysis is needed to establish its validity, for which we urge the authors to provide complete data on the confusion matrix.

"A. Menarini Diagnostics...announced at the 36th European Congress of Pathology in Florence, that they have entered into a long-term commercial agreement for the exclusive distribution of the Bladder EpiCheck test in Europe. This non-invasive CE-marked test detects primary or recurrent bladder cancer and upper tract urinary cancer."

Bladder EpiCheckâ„¢ has a high sensitivity and NPV for detecting recurrence among patients with NMIBC.

No abstract available

P=N/A; Trial completion date: May 2029 --> Dec 2028 | Trial primary completion date: May 2029 --> Nov 2028

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.

P=N/A; Trial completion date: Jul 2028 --> May 2029

Bladder Epicheck® is a useful urinary marker in the follow-up of NMIBC, with significantly high Se and NPV in the detection of recurrences, especially in cases of HG disease. Its use can reduce the number of cystoscopies required in the follow-up of NMIBC, improving the quality of life of patients and potentially increasing health economic savings.

"Nucleix...announced that the results from the company's North American pivotal clinical study evaluating the performance of Bladder EpiCheck® as a non-invasive and objective novel methylation-based PCR urine test for the surveillance of non-muscle invasive bladder cancer (NMIBC) recurrence were presented in a podium presentation at the American Urological Association (AUA) Annual Meeting 2024 in San Antonio, Texas. The data presented demonstrated Bladder EpiCheck’s potential to improve timely disease recurrence detection and compliance with NMIBC surveillance."

P=N/A; Overall trial duration is estimated at 5 yr from when the study opens to enrollment until completion of data analyses. The trial is registered at clinicaltrials.gov (NCT05796375).

Due to its high sensitivity for HG tumors, the Bladder Epicheck® Test can be used in diagnosis and treatment decision-making of UTUC. Furthermore, it could be very useful in follow-up of UTUC, after endoscopic treatment to postpone or avoid unnecessary endoscopic exploration. Even if further studies are needed to validate these findings, Bladder Epicheck® could be a promising clinical tool for detection of UTUC.

BE performance could improve timely disease recurrence detection and compliance with NMIBC surveillance. BE's high HG NPV supports the use as a rule-out test for HG disease. With high specificity and PPV, BE's false positive rates are low, potentially minimizing unnecessary downstream procedures and patient anxiety.

"Based on the results of this simulation, a marker-supported follow-up of patients with HR NMIBC is safe and offers the option to significantly reduce the number of WLCs. Further research focusing on prospective randomized trials is needed to finally find a way to implement urine markers into clinical decision-making."

In the follow-up for NMIBC, for patients for whom a BE test is planned, a combined approach of cytology and a methylation test is recommended in order to repeat the BE test with an invalid result only in those cases with a cytological diagnosis of atypical urothelial cells (AUC) suspicious for high-grade urothelial carcinoma (SHGUC) and high-grade urothelial carcinoma (HGUC).

P=N/A; Not yet recruiting --> Recruiting | Initiation date: Aug 2023 --> Nov 2023

Bladder EpiCheck demonstrated excellent and consistent performance for NMIBC surveillance across pivotal and independent studies performed in various populations and labs. The high HG NPV supports the use of Bladder EpiCheck as a rule-out test for HG disease. With a high specificity and PPV, Bladder Epicheck's false positive rates are low, potentially minimizing unnecessary downstream procedures and patient anxiety.

"Nucleix...announced it has been informed it will receive national reimbursement approval from The Dutch Healthcare Authority (NZA) in the Netherlands, effective January 1, 2024, for its CE-marked Bladder EpiCheck^® test for detection of primary or recurrent bladder cancer and upper tract urinary cancer."

"Nucleix...announced participation in the Association Francaise d'Urologie (AFU) Registry of the Therapeutic Management and Follow-Up of Non-Muscle-Invasive Bladder Cancer (TVNIM-AFU). The registry will evaluate the diagnostic performance of selected urine biomarkers in French patients and compare them to the results of bladder endoscopies (cystoscopy) performed over two years for routine follow-up of NMIBC. The registry is open to all urologists who are members of the AFU to include patients undergoing tumor resection."

P=N/A; N=168; Completed; Sponsor:Nucleix Ltd.

This review assesses the importance of methylation analysis and the Bladder EpiCheck test as urinary biomarkers for diagnosing urothelial carcinomas in patients in follow-up for NMIBC, helping cytology and cystoscopy in doubtful cases. A combined approach of cytology and methylation analysis is suggested not only to diagnose HGUC, but also to predict clinical and histological recurrences.

No abstract available

No abstract available

No abstract available

"Nucleix...has received 510(k) clearance from the U.S. Food and Drug Administration (FDA) to market Bladder EpiCheck® for use as a non-invasive method for surveillance of tumor recurrence in patients previously diagnosed with non-muscle invasive bladder cancer (NMIBC), in conjunction with cystoscopy....Bladder EpiCheck is a highly sensitive and specific test that analyzes subtle disease-specific changes across 15 methylation markers that are associated with bladder cancer. The test is commercially available in Europe and is the first of its kind methylation-based urine test performed on a qPCR platform to be cleared by the FDA....Nucleix is evaluating strategic partnerships and other market access activities for the commercial launch of Bladder EpiCheck in the United States."

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.

P=N/A | N=240 | Not yet recruiting | Sponsor: White River Junction Veterans Affairs Medical Center

"Bladder-Epicheck® and Urovysion®FISH along with cytology could be a helpful ancillary method in the diagnosis and follow-up of UTUC while due to its low specificity Xpert®-BC Detection seems to be of limited usefulness."

To the best of the authors' knowledge, this is the first study in which patients at high risk for HGUC were stratified using the Bladder EpiCheck EpiScore. The results validate this methylation analysis tool as a useful method for predicting recurrent HGUC during the follow-up of patients with nonmuscle-invasive bladder carcinoma.

No abstracts available

No abstracts available

To conclude, the BE can be used to reduce the costs of NMIBC follow-up, with a small delay in diagnosis of recurrent disease.

The EpiCheck (test showed very high diagnostic values, higher than the currently, gold standard. The test might clinically improve the BCa management in terms of, reduced number of inconclusive/suspicious reports of cytology and endoscopy, reduced number of further examinations, reduced associated patient and economic.

We demonstrated the usefulness of a DNA methylation test in the follow-up of patients diagnosed with urothelial carcinoma. The methylation test also helps to diagnose urothelial cell atypia.