There are numerous intravesical treatment options for those patients with NMIBC who experience BCG failure; however, the success rates of each are limited. From a purely oncologic standpoint, radical cystectomy is the most effective treatment in these individuals. However, radical surgery for high-risk NMIBC may be considered overtreatment for many patients and, as a result, there is substantial interest in bladder-sparing treatments for appropriately selected individuals. Options for intravesical treatment for post-BCG failure can be grouped broadly into three categories: further immunotherapy, chemotherapy, or device-assisted therapy.
In terms of immunotherapy, repeat administration of BCG is an important option, as up to 50% of patients who receive a second course of BCG experience a complete response.9 Additionally, Interferon-α (IFN-α) may be added to BCG as a means of enhancing the immune response produced by BCG. In one large trial of patients who failed BCG, the administration of BCG plus IFN-α resulted in a 45% disease-free rate at 24 months. Although patients failing only one prior course of BCG fared better than those who had received two courses of BCG, BCG plus IFN-α was still effective for select patients in the latter group when at least one year had elapsed between disease recurrences.10 Mycobacterial cell-wall-DNA complex (MCC), composed of mycobacterial cell walls complexed to mycobacterial DNA on the cell-wall surface, is another immunogenic treatment which appears to have efficacy in BCG failures. One study reported a complete response rate of 27% to 62% in the post-BCG setting, depending on dose.11 Treatments were well tolerated, and toxicity appeared to be less than would be anticipated with BCG. There is currently an ongoing, multicenter Phase 3 trial in NMIBC patients with recurrent disease or refractory to BCG which compares MCC to MMC. That target accrual for this study is 450 patients, and it has a projected completion date of November 2013. Other immunologic agents under investigation include tremelimumab (a CTLA-4 inhibitor), CG0070 (a cancer-selective virus expressing GM-CSF), and Bexidem (an autologous activated macrophage preparation).