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 biomarkersperhaps 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, and that most receive continual maintenance care from their urologists.
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.