title: Intravesical immunotherapy in nonmuscle invasive bladder cancer.
abstract: BACKGROUND
  Nonmuscle invasive urothelial cell carcinoma is the most frequent malignancy of the urinary bladder. The high recurrence rate (up to 80%) and risk of progression (up to 30%) reflect the need for long-term follow-up and sometimes multiple interventions. To reduce the rate of recurrences and tumor progression, intravesical immunotherapy, especially the use of Bacille Calmette-Guerin (BCG), represents the gold standard adjuvant treatment of high-risk nonmuscle invasive bladder cancer (NMIBC). This article reviews the role of BCG therapy and several promising new immunotherapeutic approaches such as mycobacterium phlei cell wall-nucleic acid complex, interleukin-10 (IL-10) antibody, vaccine-based therapy, alpha-emitter therapy, and photodynamic therapy checkpoint inhibitors.
  
  
  METHODS
  A systematic literature review was performed using the terms (immunotherapy, NMIBC, BCG, and intravesical) using PubMed and Cochrane databases.
  
  
  RESULTS
  BCG represents the most common intravesical immunotherapeutic agent for the adjuvant treatment of high-risk NMIBC. Its use is associated with a significant reduction of recurrence and progression. Patients with NMIBC of intermediate and high-risk benefit the most from BCG therapy. To achieve maximal efficacy, an induction therapy followed by a maintenance schedule should be used. Full-dose BCG is recommended to obtain ideal antitumoral activity and there is no evidence of a reduction of side effects in patients treated with a reduced dose. There are multiple new approaches and agents in immunotherapy with potential and promising antineoplastic effects.
  
  
  CONCLUSIONS
  The beneficial effect of BCG is well documented and established. To reduce the tumor specific mortality, it is essential to follow guideline-based treatment. In patients with BCG-failure, there are new promising alternatives other than BCG but BCG remains the gold standard at this stage.
authors.affiliation: Department of Urology, LMU Munich, München, Germany.
authors.forename: Jan-Friedrich
authors.initials: JF
authors.lastname: Jokisch
authors.affiliation: Department of Urology, LMU Munich, München, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Karl
authors.affiliation: Department of Urology, LMU Munich, München, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Stief
keywords: Bacillus Calmette-Guerin; bladder cancer; immunotherapy