Urine test for TERT promotor mutations predicts bladder cancer recurrence

Last Updated: 2017-07-20

By Reuters Staff

NEW YORK (Reuters Health) - Testing for mutations of the telomerase reverse transcriptase (TERT) gene in urine shows promise as a non-invasive tool for detecting recurrence in urothelial bladder cancer (UBC), new research shows.

"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," Dr. Alain Ruffion of the University Hospital of Lyon's Oncology Institute said in a press release from the British Journal of Cancer, which published the findings online on July 6.

UBC recurrence is frequent, and urine cytology plus cystoscopy is considered the gold standard for patient monitoring, Dr. Ruffion and his colleagues note in the report. But while cytology is highly specific, its sensitivity is low, making it less useful for patients with low-grade disease, they add.

Also, they note, both cytology and cystoscopy are interpreted subjectively. While some urinary biomarkers have been proposed with more sensitivity than urine cytology, their specificity is low, especially in patients with chronic urinary infection or inflammation.

When functioning normally, TERT shuts down in older or damaged cells, leading to senescence, the researchers explain. Cancer cells develop TERT mutations that boost the gene's activity and prevent cell death, and these TERT promoter mutations are known to occur in all stages of bladder cancer.

To test the prognostic value of TERT promotor mutations in urine, the researchers looked at 348 patients who underwent transurethral bladder resection to treat UBC and 167 controls. Overall, 80.5% of the bladder cancer patients had TERT mutations.

Sensitivity was 80.5% and specificity was 89.8%, and neither was affected by inflammation or infection. Patients who tested positive for the TERT mutations after surgery were more likely to have remaining carcinoma in situ.

In 100 patients with non-muscle-invasive UBC followed for at least six months, those who tested positive for TERT mutations were 5.34 times as likely to have recurrence (p=0.0004). Recurrence was also more likely with a positive TERT test in patients with negative cystoscopy.

"Results of this large cohort study demonstrate that detecting TERT promoter mutations in urine is a non-invasive and sensitive way to detect UBC lesions even of low-grade where cytology is not sensitive enough," the researchers write. "TERT may help to detect recurrence earlier and to better adapt follow-up frequency and treatment."

SOURCE: http://bit.ly/2vEIPIr

Br J Cancer 2017.