Genetic and molecular markers in the prognosis of bladder cancer

The objective of this consensus review was to evaluate the prognostic potential of tumor markers in the management of bladder cancer. The primary focus was on methodologic considerations related to the clinical use of tumor markers. To be of clinical value, tumor markers must add prognostic information to current staging (TNM) and grading systems. Moreover, to be introduced in routine clinical practice, promising tests based on well-designed studies must be validated in multicenter trials using testing procedures that have been standardized. They must also be evaluated in the context of their clinical utility, which consists of study end points that may lead to an altered patient management. Despite significant progress in the development and evaluation of tumor markers for bladder cancer, it is not yet possible to make firm recommendations about any of them. The review provides an assessment of the current status of the most promising tests, which should be the focus of international collaborative studies to validate them urgently. The risk of recurrence of superficial bladder tumor can be evaluated by tumor features such as number, size, grade and stage. Markers, such as M344 antigen and proliferative index, may provide further refinements. Availability of highly sensitive noninvasive diagnostic tests will help implementing different follow-up schedules in low-risk patients. Validating the molecular phenotypes that provide a strong indication for the aggressive potential of superficial tumors represents one of the best opportunities for decreasing bladder cancer mortality by allowing aggressive treatment at an early stage most likely curable. The metastatic potential of invasive bladder cancer can be further evaluated by the analysis of cell cycle regulatory proteins p53, retinoblastoma (Rb), and possibly p21. In addition, T138 antigen and tumor angiogenesis show promising potential. The p53 protein expression appears to be important in predicting response to systemic chemotherapy, although the exact significance still remains to be clearly demonstrated. Several tumor marker tests will bring additional information to existing staging and grading systems and further characterize the biological potential of tumors. Pivotal international validation studies will accelerate their translation to routine clinical practice. Our understanding of tumor biology has evolved rapidly during the past decade, resulting in the identification of nu