A urine test of telomerase reverse transcriptase (TERT) was found to be a reliable predictor of recurrence in non–muscle-invasive bladder cancer (NMIBC), according to a new study.
“The association of urine cytology and cystoscopy is the current gold standard to detect recurrence and monitor urothelial bladder cancer (UBC),” wrote study authors led by Françoise Descotes, PhD, of Centre Hospitalier Lyon Sud in France. Urine cytology is non-invasive and cheap, but is unsuitable for detecting low-grade lesions; cystoscopy results can vary with users. “Therefore objective biological markers are required.”
TERT is responsible for telomere maintenance, and TERT promoter mutations have been described at high frequency in bladder tumors. The new study included TERT urine analysis from 348 patients; 275 patients had NMIBC and 61 had MIBC, while 12 had carcinoma in situ. Results of the analysis were published online ahead of print in the British Journal of Cancer.
The overall TERT mutation rate was 80.5%, and TERT positivity was stage independent. TERT positivity had a higher sensitivity for detection of UBC than urine cytology (80.5% vs 33.6%; P < .0001). Specifically for MIBC, there was no significant difference between TERT and cytology (P = .0515).
The presence of TERT promoter mutation in urine was found to be strongly associated with NMIBC recurrence in 100 patients with at least 6 months of follow-up (P < .0001). The risk of recurrence was increased in those with TERT mutations by 5.34-fold (P = .0004).
That association did not persist in a multivariate analysis when associated with cystoscopy. But when patients were stratified by cystoscopy status, TERT positivity was significantly associated with recurrence in those with negative cystoscopy (46 of 100 patients; P = .034). This result was significant in spite of a small number of total events, with six recurrences, five of which were TERT mutated. There was no association with TERT positivity and recurrence in the positive cystoscopy patients.
“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 authors concluded. “TERT may help to detect recurrence earlier and to better adapt follow-up frequency and treatment.” They noted that the study’s single-center design does somewhat limit the results’ interpretation, and that defining TERT’s negative predictive value in the case of suspicious cystoscopy and positive predictive value in the case of negative cystoscopy and cytology remains important.