Role of immunotherapy in bacillus Calmette-Guérin-unresponsive non-muscle invasive bladder cancer

Urol Oncol. 2018 Mar;36(3):103-108. doi: 10.1016/j.urolonc.2017.12.020. Epub 2018 Feb 9.

Abstract

Intravesical instillation of live attenuated bacillus Calmette-Guérin (BCG) is the gold standard for patients with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC). BCG-failures include a heterogenous population of patients who share a designation of disease recurrence or progression following BCG and include patients with complete unresponsiveness to BCG, patients who respond initially but develop relapse and, in some cases, patients who are intolerant to BCG due to side effects. Given the efficacy and relatively rapid approval of several monoclonal antibodies against PD-L1 or PD-1 for advanced and metastatic bladder cancer, the role of these checkpoint inhibitors in BCG-relapsing disease at various disease stages is under consideration. Data supporting a role for immune checkpoint inhibitors is largely theoretical with limited supportive data from animal models and from clinical evidence of increased PD-L1 expression in BCG-unresponsive tumors. Current trials in BCG-unresponsive disease are underway and expected to provide insight regarding these concepts.

Keywords: BCG; Bladder cancer; Checkpoint inhibitors; Immunotherapy.

Publication types

  • Review

MeSH terms

  • Administration, Intravesical
  • Antineoplastic Agents, Immunological / therapeutic use*
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / metabolism
  • BCG Vaccine / therapeutic use*
  • Disease Progression
  • Drug Resistance, Neoplasm
  • Humans
  • Immunotherapy / methods*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / therapy*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Treatment Failure
  • Urinary Bladder / pathology
  • Urinary Bladder Neoplasms / immunology
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / therapy*

Substances

  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • BCG Vaccine
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor