Critical review of the models to study the biologic progression of bladder cancer

For transitional cell carcinoma of the bladder, clinical data indicate that invasive, metastatic tumors can arise through at least two different progression pathways. The majority of invasive, metastatic bladder neoplasms clinically present de novo, i.e., the patients have no history of malignant bladder disease. This implies that the highly malignant tumor cells either arise de novo or have undergone a rapid progression. Alternatively, a considerable fraction of patients with superficial bladder cancer process to invasive disease after a history of relatively benign superficial TCC. The molecular and cell biological basis of tumor progression is only poorly understood. Clearly, a better understanding of this progress could have profound clinical implications, since patients with superficial TCC with a high risk for progression would have to be treated more aggressively. We discuss the problems that are associated with tumor biological studies on early steps in the progression of TCC, especially from a "model system point of view."