Immunotherapy of Urinary Bladder Carcinoma: BCG and Beyond

Urothelial carcinoma of the bladder is the second most common urologic neoplasm after prostate carcinoma in the United States, with an estimated 70,510 new cases and 14,880 deaths in 2012 [1]. Global prevalence of bladder cancer is estimated at >1 million and is steadily increasing. This disease places enormous economic burden on the U.S. health care system due to its requirements of surgical resection, repeated intravesical therapies, and lifelong medical follow-up. Urothelial carcinoma accounts for 90% of bladder tumors. At the time of diagnosis, 20-25% of cases are muscle invasive (stage T2 or higher) and are typically treated with surgical resection (radical cystectomy) [2]. The remainders are confined to layers above the muscularis propria – so-called nonmuscle invasive bladder cancer (NMIBC). These cancers (also termed “superficial bladder cancer“) include tumors confined to the urothelium (Ta), tumors invading the lamina propria (T1), and carcinoma in situ (Tis, a flat erythematous lesion), occurring in 70%, 20% and 10% of NMIBC cases, respectively [2]. Transurethral resection of bladder tumor (TURBT) is the standard primary treatment for Ta and T1 lesions; however, recurrence rates for TURBT alone can be as high as 70% with up to 30% progressing to muscle invasive disease requiring cystectomy [3]. The high rates of recurrence and significant risk of progression in higher grade tumors mandate additional therapy with intravesical agents. While limiting the systemic exposure, intravesical therapy allows the destruction of residual microscopic tumor and circulating tumor cells after TURBT by exposure to therapeutic agents, thereby preventing reimplantation. To date, intravesical therapy has been used as an adjuvant treatment after TURBT to prevent recurrence and progression of the disese and is also the treatment of choice for Tis that is not feasible for TURBT.