by ecancer reporter Janet Fricker

A study presented at the 37th Société Internationale D’Urologie (SIU) meeting Lisbon, Portugal, has demonstrated that a new urine test for bladder cancer has high sensitivity and negative predictive values, opening the way for non-invasive testing to be incorporated into the diagnostic pathway.

The test, called ADXBladder, employs Enzyme-linked immunosorbent assay (ELISA) technology which is available in most hospitals, and requires just 10 mL of urine to deliver a definitive ‘yes/no’ results within three hours.

In 2012 in Europe 151,000 people were diagnosed with bladder cancer and 52,000 died from the condition.

For diagnosis, the European Association of Urology (EAU) currently recommend cystoscopy for all patients with haematuria, in conjunction with CT urography (in selected high-risk patients) or renal and bladder ultrasound.

Currently cystoscopy cannot be replaced by cytology or any other non-invasive tests.

For bladder cancer testing most current diagnostic approaches have disadvantages.

Cystoscopy is an undignified, invasive and uncomfortable procedure with around a 5% risk of causing UTIs; interpretation of cytology is user dependent; and CT urograms expose patients to ionizing radiation.

In the current study, between August 2016 and February 2017 577 patients attending diagnostic haematuria clinics at six UK centres underwent ADXBLADDER testing, with results then compared to the current diagnostic benchmark of combined cystoscopy, ultrasound and CT scanning.

The test uses standard ELISA methods to measure levels of MCM5, a protein marker of replicating cells, or cells which have the capability to replicate.

The key to the new test is that healthy cells which line the bladder (and are in contact with the urine) are terminally differentiated and so do not contain MCM5, while cancer cells are replicating cells and therefore do contain MCM5, so when these cells are shed into the urine MCM5 can be detected in the urine of cancer patients, but not in normal urine.

“This is a real game changer in the field of bladder cancer testing. Our data demonstrates this test has one of the highest sensitivities and negative predictive values of any urine test for bladder cancer diagnosis and additionally offers innovative features, such as the result being unaffected by urinary tract infections (UTIs), inflammation or the presence of blood,” said Mr. Stuart McCracken, the study presenter a Urology Surgeon from Newcastle University and Sunderland Royal Hospital, UK.

Compared to the benchmark:

• The sensitivity of ADXBladder in correctly detecting these cancers in high risk and muscle invasive groups was 95% (high risk groups 92%; muscle invasive groups 100%).

• The overall sensitivity for the study was 76% (high risk 92%; muscle invasive group 100%; intermediate risk 75%; low risk 50%).
• The overall specificity was 69%.
• The negative predictive value (NPV) was 97%

“What’s really important is that we achieved very good sensitivity in high risk patients and those with muscle invasive disease, where cancer is likely to spread quickly, and prognosis is much poorer,” said Mr. McCracken.

In the symposium Mr. Tim Dudderidge, a Urology Surgeon from University Hospital Southampton, considered how ADXBladder might be integrated into the current diagnostic pathway.

For low risk patients with non-visible haematuria, the test might be combined with ultrasound.

The additive effect of 76% sensitivity for this data and 80% sensitivity for ultrasound, he calculated, could deliver an overall sensitivity of 96.4%.

For high risk patients with visible haematuria, the test might be combined with ultrasound and cystoscopy to avoid CT scans.

“I think combination of these tests, depending on the risk of the patient will lead to reductions in unnecessary cystoscopy and CT scans,” said Mr. Dudderidge.

Reference

The symposium ‘A Breakthrough in Non-invasive Bladder Cancer’ was held at on Saturday 21st October at the Société Internationale D’Urologie meeting in Lisbon, Spain.