Advice

The technology

The technology

The Bladder EpiCheck (Nucleix) is an in vitro diagnostic urine test used to help detect bladder cancer recurrence. It is intended to be used alongside cystoscopy during surveillance regimens in people previously diagnosed with non-muscle-invasive bladder cancer (NMIBC).

The test analyses 15 DNA methylation biomarkers that are associated with bladder cancer, and determines whether the methylation patterns indicate the presence of cancer. The test is done using a urine sample (10 ml or more), collected in a hospital or community clinic, and is processed and analysed in a laboratory by a laboratory technician. The test procedure consists of the following steps:

  • The urine sample is centrifuged to create a cell pellet.

  • DNA is extracted from the cell pellet using the Bladder EpiCheck DNA extraction kit.

  • The extracted DNA is digested using a methylation-sensitive restriction enzyme provided in the Bladder EpiCheck test kit. This cleaves the DNA at specific sites if unmethylated.

  • The digested DNA is amplified by quantitative real-time polymerase chain reaction (PCR) using locus-specific primers and probes provided in the Bladder EpiCheck test kit. The Bladder EpiCheck test is designed for use with QIAGEN Rotor Gene Q and Rotor Gene Q MDx real-time PCR instrument platforms or the Applied Biosystems 7500 Fast Dx real-time PCR instrument.

  • The Bladder EpiCheck software analyses the methylation status of the 15 biomarkers and automatically produces a patient and summary report.

The Bladder EpiCheck test results contain a quantitative score for the person (EpiScore) and a positive or negative result based on this score. The EpiScore ranges from 0 to 100, with a higher score indicating more methylation. A score of 60 or over is considered positive for bladder cancer. Test results are then sent to the person's urologist.

Innovations

The technology is non-invasive and is designed to provide a simple and objective urine test to detect recurrence of bladder tumours. It uses standard laboratory equipment. Currently used methods are cystoscopy and cytology. Cystoscopy is an invasive procedure that can be burdensome to patients and the health system. Cytology is a non-invasive urine test. Both cystoscopy and cytology are subjective tests because they rely on visual evaluation and operator interpretation. The company claims that cytology has very low sensitivity for low-grade disease, and moderate sensitivity in high-grade disease. One expert who commented on this briefing stated that cytology is highly sensitive for high-grade disease and is comparable to Bladder EpiCheck. The technology is intended to increase confidence in recurrence detection and reduce the number of cystoscopies done.

Current care pathway

People who have had treatment for NMIBC need surveillance because of the risk of recurrence and disease progression. Standard follow-up care after NMIBC treatment is regular cystoscopy, which is sometimes supplemented with urinary cytology. The frequency and duration of cystoscopic follow up varies depending on the person's cancer severity and risk (see NICE's guideline on bladder cancer). Cytology is offered with cystoscopy, except for the follow up of low-risk NMIBC, when its use is not recommended. Urinary biomarkers may also be offered with cystoscopy and cytology. Experts who commented on this briefing noted, however, that these biomarker tests have not yet become part of NHS standard care.

The following publications have been identified as relevant to this care pathway:

Population, setting and intended user

Bladder EpiCheck would be used to monitor for recurrence during follow up after treatment for NMIBC.

More than 20,000 people are diagnosed with bladder cancer (invasive and non-invasive) each year in the UK (2016 to 2018; My Diagnosis Counts, Fight Bladder Cancer). Bladder cancer is 3 times more common in men (My Diagnosis Counts, Fight Bladder Cancer), but women are more likely to present with advanced stage cancer and typically have less favourable prognosis and outcomes. It is more common in older adults, with most new cases diagnosed in people aged 60 and over. In some people, NMIBC may come back after treatment (known as recurrence). Repeated surveillance with cystoscopy and cytology are done to help detect recurrence and reduce the risk of disease progression. People having regular cystoscopy may experience anxiety and procedural discomfort.

The Bladder EpiCheck test would be used in secondary care with or instead of cystoscopy, and instead of urine cytology or other urine biomarker tests currently used for detecting recurrence. Urine samples would be collected by nurses in a hospital or community clinic. The samples would be processed and analysed in a laboratory by a laboratory technician and test results sent to the person's urologist.

Costs

Technology costs

The cost per test for Bladder EpiCheck is £300 (excluding VAT). It includes the cost of shipping the urine sample to the testing laboratory. There are no costs associated with software installation. The company states that reagents in the kit have an expiry date of a year from manufacturing. If the kit or any reagents within the kit are found to be damaged, the kit will be replaced free of charge by the company.

Costs of standard care

Costs per test for standard care, including the cost of consumables and healthcare professionals' time:

  • Cystoscopy: £240 (national cost collection data 2019/20; healthcare resource group [HRG] code LB72A, diagnostic flexible cystoscopy, 19 years and over) or £1,789 (national cost collection data 2019/20; HRG code LB73Z, diagnostic flexible cystoscopy using photodynamic fluorescence).

  • Cytology: £3 (national cost collection data 2019/20; currency code DAPS01, cytology).

Resource consequences

The technology is not currently used in the UK. Launch is planned for 2022. Using the test as well as or instead of cystoscopy for monitoring during follow up may lead to an initial increase in resource use. However, the test may release resources if it results in earlier diagnoses and subsequent treatment by more accurately detecting cases of bladder cancer. It may also release resources if used as part of a modified surveillance strategy that reduces the number of cystoscopies done.

One economic study was identified (Lotan et al. 2021) comparing the cost of standard surveillance with a modified surveillance strategy (surveillance alternated between cystoscopy and Bladder EpiCheck every 3 to 6 months). Results showed that, for the UK, the modified surveillance strategy resulted in a cost saving when the cost of Bladder EpiCheck was less than £365. Using the Bladder EpiCheck test also reduced the number and frequency of cystoscopies from 5.2 tests over 2 years for standard care to 3.5 tests for the strategy using Bladder EpiCheck (assuming a specificity of 85.8% for the test).

The company states that urologists do not need training to interpret the EpiScore, but training is provided for laboratory staff running the Bladder EpiCheck test. No changes to facilities or infrastructure are needed to adopt the technology.