A newly-developed urine biomarker test can not only detect low-grade urothelial bladder cancer (UBC), but predict the likelihood of its recurrence earlier and more accurately than current cytology methods, according to a study released yesterday.
Françoise Descotes, Ph.D., Alain Ruffion, M.D., Ph.D., and colleagues at the University Hospital of Lyon in France, who developed the test, say the single biomarker assay detects mutated forms of telomerase reverse transcriptase (TERT), a protein involved in maintaining chromosome telomeres, in the urine of UBC patients.
The research team hopes that the simple, noninvasive test could help doctors detect and start to treat bladder cancer early, potentially before symptoms appear, and accurately detect disease recurrence, especially in patients with non-muscle invasive bladder cancer (NMIBC).
The team compared the TERT urine test with cytology, in 348 UBC patients. The biomarker assay demonstrated an overall sensitivity of 80.5% and specificity of 89.8% for bladder cancer detection. In contrast, the overall sensitivity of cytology was just 33.6%. Importantly, TERT assay sensitivity wasn’t affected by disease stage or grade, and the urine biomarker test was markedly more sensitive than cytology in detecting early-stage NMIBC.
Although urine cytology is cheap and easy to perform, it isn’t suitable for detecting low-grade lesions, the researchers suggested in their published paper, released yesterday as a British Journal of Cancer advance online publication, “Non-invasive prediction of recurrence in bladder cancer by detecting somatic TERT promoter mutations in urine.”
Tests in non-UBC controls, including patients with benign bladder lesions or other types of cancer, and healthy volunteers, confirmed that the TERT assay was highly specific, and didn’t generate anomalous results in cases of inflammation or infection, something that can limit the use of cytology. “Although the current gold standard is cystoscopy and cytology, it is subjective and may vary with the experience of the observers”, the authors write. “This is particularly a problem in some conditions (elderly patients or those with neurogenic bladder with a chronic urinary infection, inflammatory bladder etc.).”
The University Hospital of Lyon team also found that a positive TERT assay in patients who had undergone transurethral bladder resection (TURB) was associated with residual carcinoma in situ (CIS). CIS is usually difficult to detect using standard cystoscopy. TERT mutation was highly predictive of cancer recurrence in patients with NMIBC, including in patients with negative cystoscopy: “TERT positive-status after initial surgery increased risk of recurrence by 5.34-fold.”
“While the TERT test costs slightly more than standard cytology, it is likely to become cheaper over time, Dr. Ruffion suggests. “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.”
“TERT mutations in urine might be helpful for early detection of recurrence in UBC, especially in NMIBC,” the authors concluded. They next want to determine whether a single biomarker TERT assay could represent a useful negative or positive confirmatory test for when cytology results are inconclusive, suspicious or unreliable.