Introduction:

Markers are developed in structured studies initiated by industry but external validation by independent labs is important to evaluate performance.

Bladder EpiCheck^®, a PCR-based 15-marker methylation urine test, was recently cleared by the Food and Drug Administration (FDA) to be marketed in the USA for non-muscle invasive bladder cancer (NMIBC) surveillance as a deployable kit. The test is available in Europe and is included in the European Association of Urologists (EAU) NMIBC guidelines since 2022 [Babjuk et al. 2022]. Multiple independent studies of Bladder EpiCheck were published by various medical centers who performed the test in their local labs.

We review the results of company sponsored pivotal studies vs. the real-world results of independent studies.

Methods:

Results of the USA pivotal study were taken from the FDA site.

A literature review was performed in PUBMED on 07/06/2023 to identify all published peer-reviewed clinical studies of Bladder EpiCheck in NMIBC surveillance. The term “Bladder EpiCheck” was searched with no time limitations. All studies reporting original Bladder EpiCheck results in NMIBC surveillance were included in the analysis (see Graph 1).

Results:

The USA pivotal study (n=449) demonstrated overall sensitivity of 67%, HG (high-grade) sensitivity of 77% and specificity of 84% (see Table 1). Positive predictive value (PPV) was 65% and HG negative predictive value (NPV) was 95%. The European pivotal study (n=353) demonstrated overall sensitivity of 68%, HG sensitivity of 89% and specificity of 88%. PPV was 45% and HG NPV was 99%.

Of 21 Bladder EpiCheck peer-reviewed articles, 7 unique clinical studies on NMIBC surveillance were identified, including the European pivotal study and 6 independent studies. In a pooled analysis of the independent studies 1,211 NMIBC surveillance patients were included. Bladder EpiCheck demonstrated pooled overall sensitivity of 76%, pooled HG sensitivity of 91% and pooled specificity of 83%. Pooled PPV was 50% and pooled HG NPV was 98%.

Conclusion:

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. These consistent results, across the pivotal and independent studies, demonstrate that Bladder EpiCheck performed either in a local or a central lab, could improve timely disease detection and compliance.

Funding: N/A