Role and rationale of gene therapy and other novel therapies in the management of NMIBC.

Bladder cancer is the second most common urological malignancy with a one in 28 lifetime risk. Three-quarters of tumors are non-muscle-invasive (formerly termed superficial) at the time of presentation. Approximately half of all non-muscle-invasive bladder cancer (NMIBC) will recur and, depending on certain prognostic factors including grade, stage and presence of carcinoma in situ, a number will progress to muscle invasion. The standard of care for NMIBC is transurethral resection of bladder tumor (TURBT) to remove the mass lesion(s). Intravesical therapy of NMIBC post-TURBT therefore aims to delay/prevent recurrence and/or progression to muscle-invasive bladder cancer. While intravesical chemotherapy, such as mitomycin C, and immunotherapy, such as bacillus Calmette-Guérin are well established, there is current interest in novel therapies based on improved molecular understanding of bladder cancer. These novel therapies include gene therapy, using viral and non-viral vectors for transfer, monoclonal antibodies and direct tumoricidal viruses. While there is a sound theoretical basis for these therapies based on molecular targeting, there is little evidence in human studies that these therapies have clinical impact on NMIBC. However, it is certain that their use will be investigated further and they provide great hope for the future of NMIBC adjuvant therapy.