Combining radiotherapy and immunotherapy for prostate cancer: two decades of research from preclinical to clinical trials

Abstract

The combination of radiation therapy and immunotherapy is a novel therapeutic approach for prostate cancer. Preclinical evidence has shown that ionizing radiation can have immunostimulatory effects. Ionizing radiation can also affect the tumor microenvironment, enhance infiltration of activated T cells, and trigger an inflammatory process. Together, the combined radio-immunotherapy can enhance cancer cell kill and stimulate the host immune system, providing improved local and systemic control as well as prolongation of survival. The goal of combining radiation therapy with immunotherapy is also to improve cancer cure without an increase in treatment-related toxicity. The combined approach offers a new paradigm, whereby two local therapies, i.e., radiotherapy and in situ immunotherapy, are combined to elicit both local and systemic effects. Herein, we review the rationale for combining radiation and different immunotherapies, the interactions between tumors and the immune system, as well as immunological and abscopal effects of ionizing radiation. The preclinical and clinical trials of combined radiation therapy and immunotherapy for prostate cancer are reviewed. This combined approach holds promise in the management of prostate cancer.