PURPOSE OF REVIEW: There is a significant unmet need for efficacious second-line 
treatment options for patients who have failed bacillus Calmette-Guerin (BCG) 
therapy for nonmuscle invasive urothelial carcinoma (NMIBC). Recent advances in 
our understanding of systemic immunotherapy have transformed the management of 
advanced urothelial carcinoma and have led to the development of multiple novel 
agents. Using this insight, these agents are now being investigated for use in 
NMIBC.
RECENT FINDINGS: Although BCG has been used to treat high-risk NMIBC for 
decades, new applications of immunotherapy include the use of exogenous 
cytokines to boost immune response, vaccines to activate the immune system 
against specific tumor-associated antigens, intravesical agents that cause 
generalized local inflammation, and targeted antibodies against proteins on the 
surface of immune checkpoint inhibitors. Although most of these agents are still 
being investigated in clinical trials and are not yet considered standard of 
care, they hold significant promise in the treatment of patients with high-risk 
NMIBC.
SUMMARY: The use of immunotherapy has significantly improved survival outcomes 
in advanced urothelial carcinoma. Based on rapid advances in our understanding 
of the immune system and tumor biology, these agents are also poised to alter 
the therapeutic landscape for NMIBC dramatically as clinical trials are 
completed.