Combined radiotherapy and immunotherapy in urothelial bladder cancer: harnessing the full potential of the anti-tumor im
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TOPIC PAPER
Combined radiotherapy and immunotherapy in urothelial bladder cancer: harnessing the full potential of the anti‑tumor immune response Mame Daro‑Faye1 · Wassim Kassouf2 · Luis Souhami3 · Gautier Marcq2,4,5 · Fabio Cury3 · Tamim Niazi6 · Paul Sargos6,7 Received: 8 July 2020 / Accepted: 3 September 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Purpose Radiotherapy (RT), as part of trimodal therapy, is an attractive alternative treatment in patients with urothelial muscle-invasive bladder cancer (MIBC). There is accumulating evidence suggesting the immunomodulatory effects of RT and its potential synergy when combined with immunotherapy. The aim of this review was to report on the most recent advances on this combination, including the mechanisms of RT immunomodulation, practical approach to combining RT and immunotherapy, and ongoing clinical trials in bladder cancer. Methods Using the PubMed database, we identified articles published between March 2004 and April 2020 on the combination of RT with immunotherapy in localized or metastatic MIBC. A search of the Clinicaltrials.gov and Clinicaltrialsregister. eu/ retrieved ongoing clinical trials on the topic as well. Results Combination of RT with immunotherapy leads to immunogenic cell death and an increase in immune markers thus leading to improved tumor control. For localized MIBC, there are safety concerns related to the use of concurrent immunotherapy with hypofractionated RT, thus neoadjuvant or adjuvant immunotherapy is preferred. In the metastatic setting, the combination of multi-site RT with SBRT-like doses (≥ 6 Gy per fraction) and concurrent immunotherapy seems most efficacious at harnessing the abscopal effect. At least 25 clinical trials combining immunotherapy and RT in MIBC are currently ongoing and will answer pending questions on safety, efficacy, and practical considerations on RT scheduling, fractionation, and targets volumes. Conclusion RT has the potential to synergize with immunotherapy to improve oncological outcomes in patient with localized or metastatic MIBC. Clinical trials results are eagerly awaited. Keywords Radiotherapy · Radiation therapy · Immunotherapy · Immune checkpoint inhibitors · Urothelial carcinoma · Bladder cancer
* Paul Sargos [email protected] 1
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Univ. Lille, Inserm, CHU Lille, U1189-ONCO-THAI-Laser Assisted Therapies and Immunotherapies for Oncology, 59000 Lille, France
Department of Radiation Oncology, McGill University Health Centre, McGill University, Montreal, QC, Canada
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Department of Urology, McGill University Health Center, Montreal, QC, Canada
Department of Urology, Claude Huriez Hospital, CHU Lille, 59000 Lille, France
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Fellow of the American Society for Radiation Oncology (FASTRO), Department of Radiation Oncology, McGill University Health Centre, Montreal, QC, Canada
Department of Radiation Oncology, Jewish General Hospital, Montreal, QC, Canada
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Department of Radiation Oncology, Comprehensive Cancer Center, Instit
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