Combining Immunotherapy with Radiotherapy for the Treatment of Genitourinary Malignancies

Abstract Context Immunotherapy drugs, particularly checkpoint inhibitors, have recently been approved by the Food and Drug Administration for various malignancies. Preclinical and early clinical data show that combining these agents with radiotherapy may produce an even more potent antitumor effect in the treatment of cancer. Objective To describe the rationale, available data, and emerging data on the use of combined immunotherapy and radiation therapy in the setting of genitourinary (GU) malignancies. Evidence acquisition We performed a search of primary studies from PubMed/Medline that included combinations of the search terms "radiation therapy," "radiotherapy," "abscopal effect," "immunotherapy," "combined," and "combination." Evidence synthesis Preclinical and clinical data support both immune-stimulating and immune-suppressing effects of radiotherapy. Preclinical and clinical studies investigating the combination of radiotherapy with immunotherapy, primarily in the setting of non-GU malignancies, have suggested efficacy and tolerability. Early randomized trials combining radiotherapy and immunotherapy have demonstrated success in lung cancer. Although a trial investigating combined immunotherapy and radiotherapy use for prostate cancer did not clearly improve survival, trials are ongoing in multiple GU malignancies to identify synergy between immunotherapy and radiotherapy. Several practical and technical questions remain about the optimal combination of radiotherapy and immunotherapy. Conclusions Preclinical and clinical trials show that the combination of the immunotherapy and radiation therapy has the potential to provide a synergistic effect in treating cancer, including GU malignancies, although more work is needed to uncover the mechanism and determine the optimal delivery of this treatment. Patient summary This paper reviews evidence that immunotherapy drugs can be given together with radiation therapy to improve outcomes in cancers of the genitourinary tract. We find promising initial results and raise important questions that need to be answered before this type of treatment can be utilized successfully.