Bladder Tumor Markers: From Hematuria To Molecular Diagnostics - Where Do We Stand?

Main Category: Urology / Nephrology
Also Included In: Cancer / Oncology
Article Date: 05 Sep 2008 - 0:00 PDT

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UroToday.com - Bladder cancer is an extremely lethal disease occurring in a large number of patients each year. Most evaluations that result in the diagnosis of bladder cancer are initiated with the finding of either gross or microscopic hematuria. While the majority of patients with hematuria will not have bladder cancer, a sizeable proportion will. Furthermore, a regimen of invasive and frequent surveillance is often undertaken to evaluate for and diagnose recurrent lesions as early as possible.

A recent study has shown that in our state of Florida, USA, the rate of detection of advanced bladder cancer has very marginally decreased over the last 25 years, with the rates of detection of carcinoma in situ being markedly increased. This study found that the overall mortality rate of bladder cancer, depending on the ethnic group, has changed little over the last two decades.1 Evaluation of the SEER database for national and local statistics reveals that the mortality of bladder cancer nationally in some groups has remained quite flat over the past two decades:

As a result of the lethality of this disease, the invasive nature of testing often leading to significant discomfort to the patient, and expense of both initial diagnostic testing and monitoring for recurrence, the development of markers that may accurately diagnose primary and recurrent tumors has been a very important facet of research into bladder cancer for many years.

Recently, the growth in this field has been extremely rapid with a large number of markers being identified and tested. Globally, the markers can be divided into large subgroups of soluble antigens, cellular morphology, cell-based antigens, and genetic alterations.

Soluble antigens are markers that were once associated with urothelial cells that have dissociated from the cell and are detected in the urine. These markers do not need urothelial, either normal or malignant, for detection.

Cellular morphology is the microscopic cytologic evaluation of the urine specimen, received either in a voided or barbotaged manner. This test requires significant investment of time and expertise from a trained pathologist.

Cell-based antigens detect a variety of antigens associated with urothelial cells, including cell surface antigens, chromosomal rearrangements described in bladder cancer, and assays for ribonucleoprotein enzymes such as telomerase.

Molecular genetic alterations are the latest and a very active area of research interest. A large number of cell cycle, genetic, and angiogenesis related markers of malignant transformation and propagation have been identified. Current work in this aspect of tumor markers is focusing on identifying the markers with greatest fidelity for malignant potential, increasing the ease and cost-effectiveness of their detection, and subsequently expanding their role in clinical practice. While widespread use remains some years into the future, recent laboratory studies have been quite promising.

The use of bladder cancer tumor markers in current urologic practice is quite limited. A variety of hypotheses have been suggested for this, including access to specialized testing equipment, cost, urologists' unfamiliarity with these tests, and aversion to forgo invasive testing. While many of these barriers can be overcome, it is quite feasible that bladder cancer tumor markers will play an increasingly important diagnostic and prognostic role, and may become a very useful tool in the urologists' arsenal.

Written by Samir Shirodkar, MD, as part of Beyond the Abstract on UroToday.com

Reference:
1 Nieder AM, Mackinnon JA, Huang Y, Fleming LE, Koniaris LG, Lee DJ. Florida bladder cancer trends 1981 to 2004: minimal progress in decreasing advanced disease. J Urol. 2008 Feb;179(2):491-5

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