Molecular Markers for Diagnosis, Staging, and Prognosis of Bladder Cancer

Molecular Markers for Diagnosis, Staging, and Prognosis of Bladder Cancer

The article by Drs. Williams, Buscarini, and Stein
offers both the generalist and the specialist an excellent, in-depth review of
the current knowledge of bladder cancer molecular biology, biomarkers, and
targets for novel therapeutic intervention. This article is particularly useful
for individuals wishing to learn more about the development of the current model
for molecular progression of bladder cancer and how the current concepts of
cell-cycle regulation and disruption contribute to urothelial carcinoma. It
covers the mediation of various complex phenomena such as tumor-related
angiogenesis in an interesting and informative manner.

Translation of Tumor Markers to Patient Care

As the authors correctly point out, bladder cancer is a unique model in
humans that is ideally suited to experimental inquiry and provides an unusual
paradigm for the study of biomarkers. In a discrete aside at the end of the
article, Williams and colleagues make a subtle appeal for larger prospective
randomized trials of biomarkers—perhaps the only issue for which they might be
taken to task. That is, they are too reticent about what is arguably the most
pressing issue in the field of bladder cancer marker development: the
translation of tumor markers to the care of patients.

Because of its dichotomous biology, three-quarters of patients with
transitional cell carcinoma live with a chronically relapsing form of disease
that rarely progresses to muscle invasion or distant metastases. Patients with
invasive disease remain the minority player in transitional cell carcinoma,
while patients with superficial bladder cancer require very significant
expenditures of time and resources for initial treatment, monitoring for disease
relapse, and treatment of recurrent tumors. It is sobering to realize that an
estimated 600,000 Americans are presently diagnosed with transitional cell
carcinoma,[1] and that most receive continual maintenance care from their

Contemporary clinical practice offers few more poignant examples of a
disease, the management of which could be transformed by currently available
biomarker data. Although Stein and colleagues make it evident that much work
remains to be done to better elucidate the molecular basis of bladder cancer,
much is already known about these biomarkers and their potential for disease
detection in the clinical arena. The Food and Drug Administration (FDA) has
already approved four separate in vitro diagnostic assays as adjuncts in the
monitoring of previously diagnosed and treated patients. In April 2001, the FDA
provided a secondary approval for one assay as a first-line screening tool in
patients with symptoms that are suggestive of intravesical malignancy.

These assays are widely available, but they are rarely used because no large
prospective randomized trials have clearly demonstrated how these new
technologies might be usefully integrated into contemporary practice.
Incorporation of these promising new tests into daily patient care awaits large
and coordinated clinical efforts. Such an initiative will undoubtedly require
the involvement of governmental funding agencies, the cooperation and interest
of health maintenance organizations, and the substantial support of academic and
private medical practitioners.

Monitoring patients for recurrence of bladder cancer is really only the tip
of the iceberg. Millions of Americans have hematuria, and they are evaluated
each year by an extensive array of invasive diagnostic tests in order to rule
out malignancy. Yet contemporary estimates suggest that only 1% of patients with
hematuria in population-based studies have any form of urinary tract cancer.
Assays now exist that could potentially streamline and substantially improve the
economy of hematuria evaluations, eliminating urologic referrals and costly
endoscopic and radiographic testing. Despite the availability of these
technologies, there is little coordinated effort to determine how hematuria
evaluations might be improved.


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