Immunotherapy for Non-Muscle-Invasive Bladder Cancer: from the Origins of BCG to Novel Therapies

Abstract

Supplies of intravesical Bacillus Calmette-Guérin (BCG), the first-line treatment for most intermediate- and high-risk non-muscle-invasive bladder cancers (NMIBC), have proven unreliable over the past decade. This review considers the evolution of BCG immunotherapy for NMIBC: from the discovery of the antitumour side effects of tuberculosis and subsequently the BCG vaccine, to recent advances in novel immunotherapeutic agents. We summarize the evidence for alternative options to standard intravesical BCG therapy regimens and describe the potential for immune response manipulating drugs in the treatment of NMIBC. These new agents, including immune checkpoint inhibitors, toll-like receptor agonists and recombinant viral vectors, may provide better options in the management of NMIBC in the future.

Lay abstract

Many patients with non-invasive bladder cancers may need treatments into the bladder, including one called Bacillus Calmette-Guérin (BCG). Unfortunately, the supplies of BCG have been interrupted and somewhat unreliable since 2012. Because of this, we have been forced to look at other means of treating our patients using drugs similar to BCG. This has made us think about how BCG treatment was first developed more than 40 years ago and how it has evolved as a treatment for bladder cancer. In this article, we review the current uses of BCG and other treatments for bladder cancer and explore what the future may hold for bladder cancer treatment.

Tweetable abstract

This review explores the evolution of intravesical BCG therapy in IR- and HR-NMIBC. We also describe new and emerging immunotherapeutics in the management of NMIBC, which may become more important if the worldwide shortage of BCG continues.

Keywords::

• Bacillus Calmette-Guérin
• BCG
• bladder cancer
• immunotherapy
• review

Financial & competing interests disclosure

RT Bryan has contributed to advisory boards for Olympus Medical Systems & Janssen and undertakes research funded by UroGen Pharma and QED Therapeutics. The other authors have no financial disclosures. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

RT Bryan has contributed to advisory boards for Olympus Medical Systems & Janssen and undertakes research funded by UroGen Pharma and QED Therapeutics. The other authors have no financial disclosures. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.