A prospective blinded study involving 577 hematuria patients demonstrated that a new noninvasive test for bladder cancer has a sensitivity of 95 percent for higher-risk cancers and a negative predictive value greater than 97 percent.

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Researchers have developed a noninvasive urine test for bladder cancer.

The ADXBLADDER test, which has the potential to make noninvasive bladder testing a clinical reality, was launched at the 37th Société Internationale D'Urologie (SIU) meeting, held in Lisbon, Portugal.

"Our study demonstrates ADXBLADDER has one of the highest sensitivities and negative predictive values of any urine test for bladder cancer diagnosis," said Stuart McCracken, who presented the results at an SIU symposium.

The new test, he added, offers innovative features, including being unaffected by urinary tract infections (UTIs), inflammation, and the presence of blood.

It is also easy to use and employs Enzyme Linked Immunosorbent assay (ELISA) technology that is readily available in most hospitals. The test requires just 10 milliliters of urine and delivers definitive "yes/no" results within 3 hours.

Current diagnostic methods

In Europe, bladder cancer represents the fourth most common cancer in men and the 15th most common cancer in women, with 151,000 people diagnosed with the condition in 2012.

In order to make a bladder cancer diagnosis, the European Association of Urology currently recommend cystoscopy for all patients with hematuria, in conjunction with CT urography (in selected high-risk patients) or renal and bladder ultrasound.

At the moment, cystoscopy cannot be replaced by cytology or any other noninvasive tests. Most bladder cancer diagnostic approaches have disadvantages; cystoscopy is an undignified, invasive, and uncomfortable procedure exposing patients to the risk of developing UTIs, which are known to occur in around 5 percent undergoing cystoscopy.

On its own, cystoscopy can miss up to 30 percent of bladder tumors and has the additional disadvantages of being expensive and having lengthy waiting lists.

Cytology is known to have a low sensitivity and its interpretation is dependent on the user, while CT urogram exposes patients to ionizing radiation.

How does ADXBLADDER work?

In the study, 577 patients attending diagnostic hematuria clinics at six centers across the United Kingdom between August 2016 and February 2017 underwent ADXBLADDER testing, with results then compared with the current diagnostic benchmark of combined cystoscopy, ultrasound, and CT scanning.

ADXBLADDER uses standard ELISA methodology to measure levels of MCM5 – that is, a protein marker of replicating cells, or cells that have the capability to replicate.

The cells that line the bladder — and which are in contact with the urine — do not contain MCM5, so urine from a healthy bladder does not contain MCM5.

All cancer cells are capable of dividing and contain MCM5. So, when a tumor is present within the bladder, these cells are in contact with urine and shed into the urine stream, which then contains the MCM5 marker.

High sensitivity and specificity

The investigators found that 7.96 percent (46) of the patients had bladder cancer, while 92.1 percent (531) did not.

When compared with the benchmark, the results showed that:

  • The sensitivity — that is, the ability of the test to identify patients who have bladder cancer — of ADXBLADDER in correctly detecting these cancers in high-risk and muscle-invasive groups was 95 percent (with high-risk groups at 92 percent and muscle-invasive groups at 100 percent).
  • The overall sensitivity for the study was 76 percent (with high-risk groups at 92 percent, muscle-invasive groups at 100 percent, intermediate-risk groups at 75 percent, and low-risk groups at 50 percent).
  • The overall specificity for the study was 69 percent. Specificity, which is also called the true negative rate, measures the proportion of negatives that are correctly identified as such — that is, the percentage of hematuria patients without bladder cancer who are correctly identified by ADXBLADDER as not having bladder cancer.
  • The negative predictive value, or the proportion of patients who test negative but who are in fact positive, was 97 percent.

The future of ADXBLADDER

The investigators were not concerned by the lower sensitivity found for low-grade bladder disease.

"What's really important," said McCracken, from Newcastle University and Sunderland Royal Hospital in the U.K., "is that ADXBLADDER 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."

In the symposium, Tim Dudderidge — a urology surgeon from University Hospital Southampton in the U.K. — considered how ADXBLADDER might be integrated into the current diagnostic pathway.

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Researchers say that ADXBLADDER could be used as a 'standalone' test for some patients.

For low-risk patients with non-visible hematuria, he suggested, the test might be combined with ultrasound. The additive effect of 76 percent sensitivity for ADXBLADDER and 80 percent sensitivity for ultrasound, Dudderidge calculated, could deliver an overall sensitivity of 96.4 percent.

For high-risk patients with visible hematuria, he said, the test might be combined with ultrasound and cystoscopy to avoid CT scans. "I think [a] combination of these tests, depending on the risk of the patient will lead to reductions in unnecessary cystoscopy and CT scans," explained Dudderidge.

Also, ADXBLADDER could be used as a "standalone" test for patients who do not meet the current threshold for cystoscopy and CT scans, such as those under 60 with nonvisible hematuria or those whose hematuria has resolved after treatment for UTI infections.

"They may still want the reassurance of knowing cancer is not present," added Dudderidge.

The test might also be used for health screening for groups considered at high risk of bladder cancer, such as smokers and rubber or dye industry workers.

ADXBLADDER, produced by Arquer Diagnostics, received its CE Mark on October 11, 2017. The test is currently commercialized in U.K., France, Italy, Turkey, and the Nordic region, and it will be released to other European countries and worldwide regions next year.