Systemic therapy for bladder cancer finally comes into a new age

Abstract

Systemic therapy for bladder cancer, both localized muscle-invasive disease and metastatic disease, has seen minimal progress over the past two decades. Current approaches rely upon cytotoxic chemotherapy combinations aimed at increasing cure rates or achieving palliation and disease control, but these regimens are fraught with short- and long-term toxicities and outcomes remain suboptimal. The emergence of systemic immunotherapies that can provide durable remissions in subsets of patients with other malignancies has the potential to transform the field, and early phase trials have begun to demonstrate activity in some patients with metastatic bladder cancer. In this article, we review the current state of systemic therapy for bladder cancer and discuss the current literature and ongoing trials utilizing various immunotherapies.

Keywords: CTLA-4; PD-1; bladder cancer; checkpoint blockade; immunotherapy; neoadjuvant chemotherapy; urothelial carcinoma.

Conflict of interest statement

Financial & competing interests disclosure M Zibelman has received institutionally directed clinical trial support from Horizon Pharma. ER Plimack has served on advisory boards and as consultant for Genentech, Eli Lilly, Novartis, Pfizer and Bristol-Myers Squibb and has received institutionally directed clinical trial support from Bristol-Myers Squibb, AstraZeneca and Merck. 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.

Figures

Figure 1.. Proposed schema comparing present treatment algorithms with possible algorithms with possible algorithms in the future with immunotherapy for: (A) non-metastatic muscle-invasive bladder cancer and (B) metastatic urothelial carcinoma.

AMVAC: Accelerated methotrexate + vinblastine + adriamycon + cisplatin; GC: Gemcitabine + cisplatin; GCa: Gemcitabine + carboplatin; IT: Immunotherapy; NAC: Neoadjuvant chemotherapy; RC: Radial cytectomy; RT: Radiation therapy; SOC: Standard of care.