Intravesical Therapy for Superficial Bladder Cancer

The intravesical instillation of therapeutic agents for the treatment of localized bladder cancer began in 1903 when Herring[1] summarized his experience with silver nitrate. Since then, intravesical chemotherapy and immunotherapy have emerged as effective adjuncts to endoscopic resection for superficial transitional cell carcinoma of the bladder. Although advances in the treatment of superficial disease have been a major success story of clinical research efforts in urologic oncology, additional improvements are clearly needed to increase the proportion of patients with superficial disease who are cured and to treat patients who do not respond to current intravesical regimens. Drs. Baselli and Greenberg present an informative overview of the established intravesical therapies and provide insights into newer agents and combinations currently under investigation for the therapy and prophylaxis of superficial transitional cell carcinoma of the bladder. Prevention and Early Detection In addition to future improvements in intravesical therapy for superficial disease, new opportunities to reduce bladder cancer mortality will derive from research on bladder cancer prevention and early detection. Control of tobacco use and dietary and chemopreventive strategies have the potential to significantly reduce risk.[2-4] Over recent decades, improvements in diagnostic techniques and endoscopic technologies have led to the diagnosis of many bladder cancers at a much earlier stage, providing urologists with the opportunity to apply therapeutic interventions that are more effective than currently existing therapies for advanced disease. However, continued progress in developing cytologicand molecular-based tests of urine samples will provide opportunities to initiate treatment at an even earlier stage in a greater proportion of bladder cancer patients. Based on the results of two different screening studies of the general population,[5,6] it has been suggested that screening for bladder cancer with a combination of a hematuria home reagent-strip testing and one or more other tests may be a cost-effective strategy for large populations, particularly those at higher risk due to age and smoking history.[7] Currently, a number of tests for the early diagnosis of bladder cancer are under investigation for sensitivity and specificity in various population groups. These include the: (1) bladder-tumor–associated antigen (BTA) test; (2) BTA stat test; (3) fibrin/fibrinogen degradation products test; (4) nuclear-matrix protein (NMP 22) assay; and (5) BTA TRAK test. Research to Improve Intravesical Therapies The majority of bladder cancer patients in economically developed nations present with superficial papillary transitional cell carcinomas (70% to 80%) of low or intermediate grade. The treatment of choice for Ta and T1 lesions remains endoscopic transurethral resection. However, in most cases, resection alone will not ensure a long-term cure. Recurrence of superficial bladder cancer is typical, with approximately 50% to 70% of patients with TUR developing recurrent disease during their lifetime.[2] Moreover, in some studies, up to one-third of patients with superficial disease will ultimately experience muscle-invasive or metastatic disease, which carries a grave prognosis. The majority of patients with metastatic disease die of bladder cancer within 2 years despite the recent development of multimodality interventions and active combination chemotherapeutic regimens with improved response rates.[2] These features of bladder cancer have provided the stimulus for the development of more effective intravesical treatment strategies for superficial disease. Bacillus Calmette-Guérin (BCG), the most commonly employed immunotherapeutic agent for superficial bladder cancer, has been shown to be the superior therapy for carcinoma in situ of the