Combined radiotherapy and immunotherapy in urothelial bladder cancer: harnessing the full potential of the anti-tumor immune response
- 11 September 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in World Journal of Urology
- Vol. 39 (5), 1331-1343
- https://doi.org/10.1007/s00345-020-03440-4
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
This publication has 59 references indexed in Scilit:
- Pilot Trial of Radiation Therapy and GM-CSF in Metastatic Cancer: Abscopal ResponsesInternational Journal of Radiation Oncology*Biology*Physics, 2012
- Long-Term Outcomes of Selective Bladder Preservation by Combined-Modality Therapy for Invasive Bladder Cancer: The MGH ExperienceEuropean Urology, 2012
- Radiotherapy with or without Chemotherapy in Muscle-Invasive Bladder CancerNew England Journal of Medicine, 2012
- Late Pelvic Toxicity After Bladder-Sparing Therapy in Patients With Invasive Bladder Cancer: RTOG 89-03, 95-06, 97-06, 99-06Journal of Clinical Oncology, 2009
- Fractionated but Not Single-Dose Radiotherapy Induces an Immune-Mediated Abscopal Effect when Combined with Anti–CTLA-4 AntibodyClinical Cancer Research, 2009
- Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapyThe Journal of Experimental Medicine, 2006
- Long-Term Survival Results of a Randomized Trial Comparing Gemcitabine Plus Cisplatin, with Methotrexate, Vinblastine, Doxorubicin, Plus Cisplatin in Patients with Bladder CancerJournal of Urology, 2006
- Long-Term Survival Results of a Randomized Trial Comparing Gemcitabine Plus Cisplatin, With Methotrexate, Vinblastine, Doxorubicin, Plus Cisplatin in Patients With Bladder CancerJournal of Clinical Oncology, 2005
- The DNA damage pathway regulates innate immune system ligands of the NKG2D receptorNature, 2005
- Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediatedInternational Journal of Radiation Oncology*Biology*Physics, 2004