New urine test detects a biomarker of bladder cancer: A discussion with Dr. Jonathan Lopez

Background:
Diagnosis of bladder cancer poses a major challenge. Although the incidence rates of new bladder cancers have been decreasing in recent years, bladder cancer still accounts for about 5% of all new cancers in the United States and is the fourth most common cancer in men.

Now, researchers in France have reported a non-invasive, highly sensitive, and very simple method for detecting urothelial bladder cancer (UBC). It’s a urine test that measures a biomarker for mutations in the telomerase reverse transcriptase (TERT) promoter due to cancer.

In a recent article in the British Journal of Cancer, the researchers described how TERT mutations in urine can detect recurrence of UBC earlier and easier than current methods, especially in non-muscle-invasive bladder cancer (NMIBC).

In this interview, investigator and co-author Jonathan Lopez, PhD, PharmD, Medical Manager of the BIOGENET Platform at the University Hospital of Lyon, in Lyon, France, discusses how this biomarker test measures up to current methods of detecting bladder cancer and what further research is needed before the test can become widely available.

MDLinx: How does the TERT test compare with the current detection methods of cystoscopy and urine cytology?

Dr. Lopez: Compared with cystoscopy, it’s a non-invasive and very simple way to predict recurrences in UBC. Compared with cytology, it’s way more sensitive for detecting low-grade lesions before they become invasive. In our study, its overall sensitivity was 80.5% and its specificity was 89.8%.

MDLinx: Why was TERT a good candidate to study as a biomarker for UBC?

Dr. Lopez: TERT was known to be highly mutated in bladder cancer. Also, TERT somatic promoter mutations from urine are easy to test in a molecular biology lab.

MDLinx: What results did you find for the detection of high-grade vs low-grade tumors?

Dr. Lopez: We observed that TERT mutation prevalence was high both in high-grade and low-grade tumors, whereas cytology wasn’t able to detect these lesions.

MDLinx: Among patients with NMIBC, how did detection of TERT mutations compare with cystoscopy in regard to cancer recurrence?

Dr. Lopez: Very interestingly, we observed that TERT mutation was associated with recurrence in our cohort. In multivariate analysis, we observed that prediction of recurrence by TERT was similar to positive cystoscopy. We also observed that TERT could identify recurrence in a subset of patients who had negative cystoscopy.

MDLinx: You stated that the presence of TERT mutations in urine was a “dynamic marker of recurrence.” What does this signify?

Dr. Lopez: It means that TERT can turn negative after initial treatment and then positive again at/before relapse during the follow-up of patients. In one case that we discuss in the paper, a patient who had a transurethral bladder resection for a low-grade NMIBC presented with a positive TERT mutation, which became negative on follow-up. Seven years later, TERT became positive again, along with signs of recurrence by cystoscopy. After a high-grade tumor was resected, the patient’s urine samples have remained negative for TERT mutation for three years of follow-up. It’s worth noting that cytology remained negative throughout, from his initial tumor to the recurrence.

MDLinx: You reported that the test’s overall specificity wasn’t affected by inflammation or infection. How does this compare with other methods of detection?

Dr. Lopez: We found that detection of TERT mutation remains highly specific in inflammatory and infectious urine samples compared with other previously investigated urinary biomarkers, which are known to give false-positive results. This is important because urinary tract infections occur frequently in non-UBC patients. Furthermore, in cases of suspicious cystoscopy, TERT could help clinicians to distinguish between recurrence and inflammatory lesions.

MDLinx: What is the next step for this line of research on detecting TERT mutations in bladder cancer?

Dr. Lopez: We need a multicenter study to clearly define the negative predictive value of this test as a single marker in cases of suspicious cystoscopy and also its positive predictive value in cases of negative cystoscopy and cytology.

About Dr. Lopez: Jonathan Lopez, PhD, PharmD, is Medical Manager of the BIOGENET Platform at the University Hospital of Lyon and on the medical faculty at the University of Lyon and the Cancer Research Center in Lyon, France.