The biology and treatment of superficial bladder cancer.

Management of the superficial bladder cancer patient consists of two complementary but separate therapeutic goals: treatment of the existing tumor(s) and prevention of tumor recurrence. At present, the stage, grade, and multicentricity are the major determinants in the natural and therapeutic history of the disease. Although intravesical instillation of chemotherapeutic agents has been used for greater than 20 years, neither its exact role nor the optimal dose or schedule of administration have been established. To date, no dramatic differences in efficacy between the agents commonly used for intravesical chemotherapy, either as definitive therapy or prophylaxis, have been appreciated. These agents do appear to lower the recurrence rate as well as extend the disease-free interval. Since the most thorough experience is with thiotepa, it is the drug against which other agents should be compared in terms of both efficacy and toxicologic evaluation. Different administration schedules and methodologies need further study, such as the utility of continuous bladder irrigation, the use of sequential chemotherapeutic agents to gain cell synchronization, and the use of multiple drug regimens. Because there are multiple factors that influence the occurrence and recurrence of bladder cancer, combined modality therapy deserves testing. Modes of therapy that could be used together because they act through different mechanisms are intravesical chemotherapy, radioactive needle implants, carcinogen modifiers such as pyridoxine, chemoprotective agents such as retinoic acid, and immune stimulants such as BCG. These studies should be performed in a randomized prospective controlled fashion, which may require cooperative multi-institutional involvement to accrue adequate numbers of patients. At this time there are a number of important questions that remain to be answered concerning the treatment of superficial bladder cancer: (1) does this mode of therapy affect overall survival, (2) does prophylactic intravesical chemotherapy alter the incidence of subsequent muscle invasive disease, (3) does intravesical chemotherapy alter the sites, incidence, or responsiveness to systemic chemotherapy of subsequent metastatic disease, and (4) and what is the optimal timing and duration of prophylactic therapy from a cost-effectiveness standpoint?