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

Nature Reviews Urology volume 15, pages 251–259 (2018)Cite this article

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Abstract

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.

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Figure 1: Immunogenic effects of radiotherapy.
Figure 2: Effects of anti-PD-1 or anti-PD-L1 antibodies on antitumour immunity.

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Acknowledgements

R.W. researched data for this article, R.W. and J.H. made a substantial contribution to discussions of content, R.W. wrote the manuscript, and J.H., T.I., and A.C. edited and/or reviewed the manuscript before submission.

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  1. Division of Cancer Sciences, Richard C. Walshaw, Jamie Honeychurch, and Timothy M. Illidge are at the Targeted Therapy Group, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Sciences Centre, 555 Wilmslow Road, Withington, Manchester M20 4BX, UK.,

    Richard C. Walshaw, Jamie Honeychurch & Timothy M. Illidge

  2. and Ananya Choudhury are at the Department of Clinical Oncology, Richard C. Walshaw, Timothy M. Illidge, The Christie NHS Foundation Trust, Manchester Academic Health Sciences Centre, 555 Wilmslow Road, Withington, Manchester M20 4BX, UK.,

    Richard C. Walshaw, Timothy M. Illidge & Ananya Choudhury

  3. Division of Cancer Sciences, Ananya Choudhury is at the Translational Radiobiology Group, School of Medical Sciences, Faculty of Biology, University of Manchester, Manchester Academic Health Sciences Centre, 555 Wilmslow Road, Withington, Manchester M20 4BX, UK.,

    Ananya Choudhury

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Walshaw, R., Honeychurch, J., Illidge, T. et al. The anti-PD-1 era — an opportunity to enhance radiotherapy for patients with bladder cancer. Nat Rev Urol 15, 251–259 (2018). https://doi.org/10.1038/nrurol.2017.172

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