Intravesical Therapy of Superficial Bladder Cancer

Michael   D.   Melekos; George   D.   Moutzouris

Abstract

Transurethral resection (TUR) of the superficial transitional cell carcinoma (TCC) of the bladder is known to be insufficient in controlling the disease because of the unacceptable rates of recurrence, progression and ultimate cystectomy. Adjuvant intravesical chemo-and or immunotherapy is administered in an effort to enhance the efficacy of surgery alone. The initial tumor stage and grade, the multifocality of this cancer and the history of previous recurrences remain the determinant factors in survival. It is important to decide exactly which patients are at risk, and, therefore, do need treatment. Knowledge of the natural history of the disease will facilitate this decision making, although the natural history of TCC is largely unpredictable owing to tumor heterogeneity. Several cytotoxic and immune modifying agents have been used intravesically in different treatment schedules. However, despite their effectiveness, no consensus exists about the optimal antineoplastic regimen. The selection of the latter is a subject of continuous investigation. Intravesical treatment with cytotoxic drugs has been demonstrated to achieve an acceptable reduction in short- and intermediate-term recurrence rates, but has no proven ability in preventing disease progression to muscle-invasive cancer or prolonging survival. On the other hand, bacillus Calmette-Guerin (BCG) currently appears to be the most effective agent for intravesical use, especially in patients with high grade and stage neoplasms but the optimum strain, dosage and duration schedule have not been determined. Clinical trials have shown that BCG provides long-term protection from tumor recurrence, while there is evidence that it may favorably alter the progression rate of the disease with prolongation of survival. Toxicity of intravesical chemo- and immunotherapy still remains a major problem and attempts at reducing the dosage, and, thus, toxicity without affecting efficacy are underway. This review endeavors to present updated information on intravesical chemotherapy in treating superficial bladder cancer, the expanding role of intravesical immunotherapy, the recent work comparing various immunotherapeutic regimens with chemotherapeutic intravesical therapies, and the progress made towards achieving optimal treatment regimens.

Keywords: bladder cancer, transurethral resection TUR, Transitional Cell carcinoma TCC, bacillus calmette guerin BCG, Carcinoma in situ, Intravesical therapy, dysplasia, intravesical chemotherapy, thiotepa, triethylenethiophosphoramine, ethoglucid Epondyl, mitomycin C MMC, Doxorubicin Adriamycin, epirubicin, mitoxantrone, Intravesical Immunotherapy, anthracenedione, interferons INFs, Interleukin 2 IL2, natural killer NK, lymphokine activated killer cell LAK, keyhole limpet hemocyanin KLH, intravesical chemoprophylaxis, BCG Immunoprophylaxis, complete response, delayed type hypersensitivity, electromotive drug administration, isoniazid