Measuring certain enzyme activity in urine shows promise for detection of bladder cancer

October 25, 2005

Measurement of an enzyme level (telomerase activity) in urine appears useful for detection of bladder cancer in men, according to a study in the October 26 issue of JAMA.

The incidence of human bladder cancer has greatly increased over the last few decades, with more than 60,000 new cases diagnosed each year in the United States alone, and now represents the 4th most common malignancy in men and the 10th most common in women, according to background information in the article. At present, about 20 percent of patients die each year, but when the disease is diagnosed and treated in the early stage, the chances of survival are good, indicating the importance of a timely and accurate diagnosis.

Established approaches for detecting bladder cancer are either invasive and costly or have limited sensitivity, highlighting the need for the development of a noninvasive, reliable, and simple test to increase the rate of detection of bladder cancer. Among the markers investigated for this purpose has been telomerase (a certain enzyme) activity in urine.

Maria Aurora Sanchini, M.Sc., of Morgagni-Pierantoni Hospital, Forlì, Italy, and colleagues conducted a study to define the diagnostic accuracy of different telomerase activity cutoff values in terms of sensitivity and specificity. The study included 218 men (84 healthy individuals and 134 patients at first diagnosis of histologically confirmed bladder cancer), recruited between March 2003 and November 2004 in Italy. Urine telomerase activity was determined using a highly sensitive telomeric repeat amplification protocol (TRAP) assay. Urine samples were processed for cytological (cell) diagnosis and TRAP assay. The diagnosis of bladder cancer was based on bioptic and cystoscopic examinations (direct visual examination of the urinary tract). The performance of the TRAP assay to detect urine telomerase activity was compared to urine cytology as an aid to early cancer detection.

Using a 50 arbitrary enzymatic unit (AEU) cutoff value, in the overall series, there was 90 percent sensitivity and 88 percent specificity. Specificity increased to 94 percent for individuals aged 75 years or younger. The same predictive capacity of telomerase activity levels was observed for patients with low-grade tumors or with negative cytology results. The sensitivity of urine telomerase activity in detecting bladder tumors was similar in the subgroups of patients with different tumor grades at all AEU cutoff values. In particular, at 50 AEUs the sensitivity was 93 percent, 87 percent, and 89 percent for grades 1, 2, and 3, respectively.

"The test we developed requires a small amount of urine; is noninvasive, inexpensive, and easy to perform; and permits a quantitative evaluation of telomerase activity in cellular extracts from urine. Furthermore, it is objective, reproducible, and specific and is not reliant on the expertise of the cytopathologist. Indeed, one important advantage of this test is its proven ability to also identify low-grade tumors, which often escape detection, thus largely contributing to false-negatives in cytologic examination," the researchers write.

"However, notwithstanding the validated optimal diagnostic accuracy of the test, it is not recommended for use in routine screening programs because of the low incidence of bladder cancer, and should be aimed at high-risk subgroups. Specifically, smokers have about a 3-fold increased risk of developing bladder cancer compared with nonsmokers," the authors add.

"In conclusion, we believe that our telomerase activity urine assay, with the reliability verified in pilot and confirmatory studies, represents a promising and potentially important contribution to the early diagnosis of bladder carcinoma, in particular for high-risk subgroups. Further prospective studies on larger patient populations are needed to assess the promising diagnostic role of urinary telomerase and to define the ability of this assay to detect low-grade tumors and disease recurrence before it becomes clinically evident, which is especially important in a tumor characterized by a high relapse rate."
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(JAMA.2005; 294:2052-2056. Available pre-embargo to the media at www.jamamedia.org)

Editor's Note: For funding/support information, please see the JAMA article.

The JAMA Network Journals

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