Intensive research on the molecular biology of bladder cancer has provided great insight into the disease over the last decade and is beginning to shape clinical practice. The article by Williams, Buscarini, and Stein is a thorough review of biologic markers and the current state of the art in bladder cancer management. The prolific work from the group at the University of Southern California (USC) has provided significant insights into cell-cycle regulatory markers and their role in molecular staging. This group’s solid basic research and substantial radical cystectomy database serve as worthy models for translational investigations.
Molecular medicine holds the promise that clinical outcomes will be improved by directing therapy toward the mechanisms and targets associated with the growth of an individual patient’s tumor. Translation into clinical practice has been slow, however. The literature is confusing at times, and the lack of standardization in areas such as immunohistochemistry limits reproducibility across clinical labs. Clinicians continue to rely on traditional morphologic and histologic parameters in order to assess tumor biology and prognosis.
Evaluating New Markers
The case of p53, which is altered in at least one-half of bladder cancers, is illustrative. A Medline literature search combining the terms "p53" and "bladder cancer" yields 543 articles published in English. Several relatively large series with multivariate analyses suggest that alteration of the p53 pathway provides valuable prognostic information. Nonetheless, evidence for and against almost every aspect of the role of p53 allows the support of almost any point of view.
It is also apparent that different abnormalities in p53 may lead to different clinical outcomes. Translation into clinical practice requires prospective clinical trials, and a collaborative group from USC, Baylor College of Medicine, and the University of Chicago have initiated a National Cancer Institute-funded multicenter, multinational clinical trial to evaluate p53 and other markers in patients treated with radical cystectomy for cancers pathologically confined to the muscularis propria or lamina propria. This study will attempt to answer these questions:
- Do p53 alterations in bladder-confined transitional cell carcinoma significantly increase the risk of recurrence and death?
- Does adjuvant chemotherapy improve survival in patients with p53 alterations?
The study will also create a repository of archival tissue for the examination of other markers (eg, retinoblastoma [Rb] gene) and cell-cycle regulatory proteins (eg, p16 and p21).
Developing Targeted Therapies