Telomerase testing

Measurements of the level of telomerase activity in urine can be used to detect early stage bladder cancer in men, according to a case–control prospective study published in the Journal of the American Medical Association.

Bladder cancer represents the fourth most common malignancy in men and the tenth most common in women, and approximately 20% of patients with this cancer die each year. When the disease is diagnosed and treated in the early stages, the chances of survival are good, indicating the importance of early detection for this cancer type.

Current approaches for detecting bladder cancer are invasive, costly or have limited sensitivity. A reliable, simple and non-invasive test is therefore urgently needed. One potential marker of bladder cancer is telomerase activity, which can be detected in urine samples using the highly sensitive telomeric repeat amplification protocol (TRAP) assay.

Maria Aurora Sanchini and colleagues conducted a study to define the diagnostic accuracy of different telomerase activity cutoff values in terms of sensitivity and specificity. The study, which was performed in Italy, included 218 men — 84 healthy individuals and 134 patients at first diagnosis of histologically confirmed bladder cancer. Urine samples were analysed using both cytological assays and the TRAP assay, and the results were compared. Patients were diagnosed with bladder cancer based on bioptic and cystoscopic examinations (direct visual examination of the urinary tract).

Using a 50 arbitrary enzymatic unit (AEU) cutoff value established in an earlier pilot study, the authors validated their initial results in a new set of patients. In these patients, the TRAP assay could detect bladder tumours with 90% sensitivity and with 88% specificity. Specificity increased to 94% for individuals aged 75 years or younger. The TRAP assay was also able to detect telomerase activity in patients with low-grade tumours or with negative cytology results.

The sensitivity of the TRAP assay in detecting bladder tumours was similar in the subgroups of patients with different tumour grades at all AEU cutoff values. In particular, the sensitivity at 50 AEUs was 93%, 87% and 89% for patients with grades I, II or III tumours, respectively.

The authors suggest that the assays should not be recommended for use in routine screening programmes because of the low incidence of bladder cancer. Rather, the TRAP assay should be aimed at high-risk subgroups, such as smokers, who have an approximately threefold increased risk of developing bladder cancer compared with non-smokers, or patients with symptoms of bladder cancer. It can also be used to monitor recurrence in patients who have been previously treated for bladder cancer.

Further prospective studies on larger patient populations are needed to better determine the ability of this assay to detect low-grade tumours and disease recurrence. This is especially important, as this tumour type is characterized by a high relapse rate.