The natural history of bladder cancer. Implications for therapy

Transitional cell carcinoma of the bladder is comprised of a variety of cancer diatheses that manifest a spectrum of distinct biologic potentials. Although these diseases have traditionally been classified as "superficial" and "muscle invasive" on the basis of their histologic appearance (depth of penetration of the "bladder wall" and corresponding prognosis) the pathways presumably followed by the various forms of these cancers imply an even greater complexity. These disparate pathways may reflect different events in carcinogenesis, which may determine subsequent development and risk for either recurrence or progression. In addition, biologic activity and malignant potential for each type of cancer may be associated with distinctive molecular and genetic alterations. These considerations may provide an opportunity to expand traditional staging systems in creating molecular profiles that may more precisely characterize the biologic potential of these tumor diatheses. Although there are far more questions than answers concerning how these alterations may effect the natural history of bladder cancer, molecular-based identification of bladder cancer patients at greatest risk for progression may ultimately improve clinical management.