The anti-PD-1 era — an opportunity to enhance radiotherapy for patients with bladder cancer

The introduction of immune checkpoint inhibition has improved the outcomes of a subset of patients with muscle-invasive bladder cancer (MIBC); however, the majority of patients fail to respond to this approach. In this perspective, the authors describe the evidence for use of radiotherapy in combination with immune checkpoint inhibition to enhance the immunogenicity of patients' tumours and therefore enhance responsiveness to immune checkpoint inhibition in patients with advanced-stage MIBC. An urgent need exists to improve the outcomes of patients with muscle-invasive bladder cancer (MIBC), and especially of those with metastatic disease. Treatments that enhance antitumour immune responses — such as immune-checkpoint inhibition — provide an opportunity to do this. Despite initial success, durable response rates in patients with advanced-stage MIBC treated with novel inhibitory antibodies targeting programmed cell death protein 1 (PD-1) or its endogenous ligand programmed cell death 1 ligand 1 (PD-L1) remain low. Radiotherapy is part of the management of bladder cancer in many patients. Evidence that radiotherapy has immunogenic properties is now available, but radiotherapy-induced immune responses are often negated by immunosuppression within the tumour microenvironment. Anti-PD-1 or anti-PD-L1 antibodies might enhance radiotherapy-induced antitumour immunity. This effect has been demonstrated in preclinical models of bladder cancer, and clinical trials involving this approach are currently recruiting. Combination treatment strategies provide an exciting opportunity for urological oncologists to not only improve the chances of cure in patients undergoing radical treatment for MIBC, but also to increase long-term response rates in those with metastatic disease.