Adjuvant intravesicular pharmacotherapy for superficial bladder cancer

In 1990, bladder cancer, excluding carcinoma in situ, was estimated to contribute 49,000 cases of cancer. In men 75 years old or older, it became the fifth leading cause of cancer deaths. Of patients with bladder cancer, 75%-80% initially present with superficial bladder tumors. Treatment of these tumors has three objectives: 1) to eradicate existing disease, 2) to provide prophylaxis against tumor recurrence, and 3) to avoid deep invasion into the muscle layers of the bladder. Transurethral resection is the primary treatment to eradicate superficial bladder tumors, but 40%-80% of these tumors recur. Because of these high recurrence rates, adjuvant intravesicular pharmacotherapy with cytotoxic and immunomodulatory drugs has gained widespread use. The past two decades of clinical investigations in superficial bladder cancer have provided valuable information on the biology and treatment of the disease. Multivariate analyses have indicated that tumor grade and stage are the most important prognostic variables commonly available to the clinician to identify the patient at greatest risk of developing muscle-invasive or metastatic bladder cancer. These studies have also identified groups at low risk for tumor recurrence and invasive bladder cancer. Randomized trials have shown that recurrence rates are decreased by adjuvant intravesicular pharmacotherapy with a number of drugs: bacillus Calmette-Guérin vaccine (BCG), doxorubicin, ethoglucid (Epodyl), mitomycin-C, teniposide, and thiotepa. However, few studies indicate that adjuvant intravesicular pharmacotherapy can prevent progression to invasive bladder cancer in the high-risk patient with superficial bladder cancer. Additional clinical trials are needed to determine whether such therapy can prevent invasive and metastatic bladder cancer and improve disease-free survival in this group. In addition, the identification of tests (e.g., monoclonal antibody tests, chromosomal analyses, and tumor marker assays) that can help to identify high-risk patients is needed to better develop therapeutic strategies for superficial bladder cancer.