Prospects and progress of immunotherapy for bladder cancer

ABSTRACT

Introduction: With recent advances in immunooncology and the introduction of checkpoint inhibitors into clinical practice for many cancers, the treatment landscape of urothelial carcinoma has changed dramatically and will continue to change further. Currently, a number of compounds and combinations are under investigation in numerous clinical trials and various clinical scenarios for bladder cancer.

Areas covered: In this review, the authors provide an overview of the history and rationale for immunotherapy in bladder cancer. They also provide the currently available data evaluating checkpoint inhibitors for bladder cancer, and discuss ongoing trials and future perspectives for urothelial carcinoma treatment.

Expert opinion: The introduction of checkpoint inhibitors into the management of bladder cancer marks a significant milestone for this disease. Checkpoint inhibitors have the potential to impact patients across multiple disease states from non-muscle-invasive disease to metastatic tumors refractory to conventional treatment. That being said, validated biomarkers, including genetic signatures, to accurately predict response, and the establishment of optimal sequencing and combination of these immunotherapeutic agents with chemo/radiotherapy are urgently needed.

KEYWORDS:

• Bladder cancer
• metastatic
• NMIBC
• MIBC
• immunotherapy
• checkpoint inhibitors

Article highlights

• The armamentarium for treatment of bladder cancer has been very limited, especially in case of progression and resistance to intravesical Bacillus Calmette-Guérin (BCG) immunotherapy in non-muscle invasive bladder cancer (NMIBC) and platinum- based chemotherapy in muscle-invasive (MIBC) locally advanced or metastatic bladder cancer (mUCB).

• Intravesical BCG immunotherapy still remains the standard of care for patients with intermediate and high-risk NMIBC in spite of high disease recurrence/progression rates and many obstacles such as low patient compliance, relatively high toxicity profile and limited market availability of BCG.

• There are many active immunotherapy trials currently recruiting and ongoing in patients with MIBC in the neoadjuvant and adjuvant setting, although there are no results available yet with regard to efficacy and especially in comparison to cisplatinum-based chemotherapy.

• The available data on the various checkpoint inhibitors (CPIs) are very promising for both, second-line treatment, where a change of paradigm is already imminent, and potentially also for first-line treatment, with several promising registration trials.

• Pressing questions remain to be elucidated over time, especially about biomarkers predicting response to immunotherapy and optimal sequencing/combination of available immunotherapeutic agents in treatment of bladder cancer.

Declaration of interest

M Boegemann has served as an advisor for Roche, Merck Sharp and Dohme, AstraZeneca and Bristol-Myers Squibb. 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.

Additional information

Funding

This manuscript has not been funded.