Test could help detect bladder cancer recurrence

An easy-to-administer urine test looking for telomerase reverse transcriptase (TERT) mutations helps detect recurring urothelial bladder cancer, especially non-muscle-invasive bladder cancer, early on, according to a new study.

But how urologists would use this test instead of or in addition to the gold standards cystoscopy and cytology when treating bladder cancer patients remains unclear, according to Badrinath Konety, MD, MBA, of the University of Minnesota, Minneapolis, who was not involved with the study.

Researchers studied 348 subjects treated by transurethral bladder resection for urothelial bladder cancer, to determine whether TERT mutation detection in urine would predict bladder cancer recurrence. They compared results to cytology and cystoscopy in 167 controls.

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They found that the TERT test’s overall sensitivity was 80.5% and specificity was 89.8%. Inflammation or infection did not greatly impact results, according to the authors.

A positive postsurgery TERT test was associated with residual carcinoma in situ. The test reliably and dynamically predicted non-muscle invasive bladder cancer recurrence. A positive TERT test after initial surgery increased recurrence risk by 5.34-fold, and was associated with recurrence in patients with negative cystoscopy.

Cytology detected the cancer’s return in 34% of patients, according to the study, which was published online in the British Journal of Cancer (July 6, 2017).

“The standard cytology test needs a doctor to look down a microscope to read the results, but the TERT test is read by a machine which is simpler, more accurate, and available to use straightaway. While the TERT test costs slightly more than standard cytology, it is likely to become cheaper over time,” said study author Alain Ruffion, MD, PhD, of the University Hospital of Lyon's Oncology Institute, in Lyon, France, in a Cancer Research UK press release.

Next: Dr. Konety discusses findings

Dr. Konety said the study is good in that it has a moderate number of patients and is based on what research has clearly shown: Telomerase reverse transcriptase levels rise in people with bladder cancer.

For urologists managing these patients, however, there remain hurdles in the TERT test’s general use.

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“I think we need to understand exactly how we can use this and whether these performance characteristics will hold out with a larger sample set,” Dr. Konety said.

Cystoscopy is the cornerstone of detection of non-muscle-invasive bladder cancer, he said.

“On top of cystoscopy, you could use adjuncts, such as cytology, which has been a mainstay for a long time. The advantage of cytology is if it’s positive you know there’s something there. If it’s negative, it could be wrong,” he added.

To clarify results from a cystoscopy and cytology, Dr. Konety said he might use the UroVysion Bladder Cancer Kit fluorescence in situ hybridization (FISH), which is a urine test.

“The FISH test is more of a genetic [test]. It looks for specific genetic mutations, or copy number changes for the genes,” he said. “We have found that to be particularly helpful if the cytology test comes back as atypical. The other place we use FISH is when you have a patient who had bacillus Calmette-Guérin for treatment of non-muscle-invasive bladder cancer, and we want to assess whether the patient is responding or not.”

There are other markers. Among them: Cxbladder; nuclear matrix protein number 22, or NMP22; and bladder tumor antigen, BTA.

“The BTA and NMP22 are slightly older markers which are protein based,” he said. “They’re really not very helpful in the context I just mentioned because proteins can be increased or decreased based on inflammation and a variety of other factors.”

Cxbladder, also a genetic test, looks for elevated expression of certain genes in the urine.

“It has a combination of five genes and also looks for one specific gene, which is only elevated in inflammation, which really helps determine if any changes in the urine are due to inflammation or cancer,” Dr. Konety said.

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There’s yet another test called The ImmunoCyt/uCyt+, which can enhance cytology findings, he said.

“We use that sometimes, as well. It’s not easy to get hold of,” he said.

Next: "If you really want to replace [cystoscopy], you better get a test that is really, really close to cystoscopy"

Despite the latest study on the TERT test, Dr. Konety said he continues to typically use cystoscopy, cytology, and FISH to monitor for recurrence in these patients.

“People have been trying to develop a urinary marker for the last maybe 30-plus years. There have been a ton of markers that have been investigated and many trials run. Still, marker use has not caught on,” Dr. Konety said.

The reason? How to best use these tests isn’t clear, according to Dr. Konety.

“If we’re going to do cystoscopy on everybody, and we feel that cystoscopy is really reliable and is probably the best test, then, if you really want to replace it, you better get a test that is really, really close to cystoscopy,” he said. “As studies suggest, patients are telling us that some other test has to be 90% to 95% sensitive before they’re willing to give up cystoscopy. They don’t mind undergoing the discomfort of a 10-minute procedure, as long as they know it will tell them if they have something to worry about.”

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If urologists are going to use the TERT or other test as an adjunct, then it has to have the specificity of cytology but improve upon its sensitivity, he said.

“Specificity of cytology is over 90%. And none of the other tests have come up to that level of specificity, while retaining a very high level of sensitivity,” he said.

Where a test, such as the TERT test, might also be highly useful is in people with blood in their urine, to test for bladder cancer and potentially avoid computed tomography scans and cystoscopy, according to Dr. Konety.

“That would be very beneficial because it’s a good area to focus on. Again, the test parameters have not yet gotten to that level. But they may get there,” he said.

The study was funded by the French Ministry of Health. Dr. Konety is involved in studies on tumor markers with Genomic Health.

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