Abstract
Immunotherapy for renal cell cancer (RCC) has witnessed several developments for more than two decades. Checkpoint inhibitors, including anti-CTLA-4 and anti-PD-1/PD-L1 blockers, have changed the treatment landscape for patients with advanced RCC in the past 3 years. Despite these advances, more than 55% RCC patients become resistant to different immunotherapies without other treatment combination. Among various attempts at overcoming resistance to immunotherapy, stereotactic body radiotherapy (SBRT) has been found to potentiate the activity of immunotherapy agents through several potential mechanisms, including normalization of microvessels to alleviate tumor hypoxia, improvement in efficient delivery of drugs, abundant neoantigen exposure, and recruitment of antitumor immune cells to alter the immunosuppressive tumor microenvironment. Preclinical studies and clinical case reports have predicted that the combination of SBRT, an immunotherapy, may lead to remarkable results. This review aims to provide the biological basis for the feasibility of combining SBRT to overcome immunotherapy resistance and to review the currently available clinical evidence of this combination therapy in patients with advanced RCC.
Highlights
Renal cell cancer (RCC) is the third most common urological carcinoma, and over 90% cases of RCC in adults is clear cell in histology [1, 2]. e prognosis of RCC cases depends on the disease stage, tumor properties, the state of tumor metastasis, accurate diagnosis, proper treatment, and so on [2]
An analysis of radiographic and symptomatic RT responses in 27 consecutive RCC patients with 37 lung lesions found that rates of radiographic local control with stereotactic body radiotherapy (SBRT) were much higher than conventional fractionated radiation (CFRT) [37]
A prospective phase I trial suggested that SBRT might be an alternative to cytoreductive nephrectomy for inoperable patients with advanced RCC [39]. e median tumor size was increased 17.3% at 5.3 months, and the median overall survival (OS) was increased at 6.7 months [39]
Summary
Renal cell cancer (RCC) is the third most common urological carcinoma, and over 90% cases of RCC in adults is clear cell in histology [1, 2]. e prognosis of RCC cases depends on the disease stage, tumor properties, the state of tumor metastasis, accurate diagnosis, proper treatment, and so on [2]. Advance and metastatic cases still carry a poor prognosis with a 5-year survival of about 9–12% [3]. Erapeutic options for advanced RCC patients should be based on histology (clear cell or not clear cell) and the most widely used prognostic factor model is from the Memorial Sloan Kettering Cancer Center (MSKCC) with stratification in three prognostic categories (favorable, intermediate, and poor risk) [5]. Development and progression of advanced RCC have been slowed or even arrested through immune checkpoint inhibitor (ICI) combination therapy (ipilimumab plus nivolumab), which, in patients with intermediate or poor risk, showed a better overall survival (OS) than VEGF target therapy recently [6]. Stereotactic body radiotherapy (SBRT), which comprises high doses of radiation delivered in fractions (usually ≤5), has evolved to become an important treatment strategy for both primary lesions and metastatic diseases in different organs for RCC patients. Several key biological pathways triggered by SBRT prime the system immune to eliminate tumor cells. erefore, SBRT and immunotherapy display synergistic effects, which are reviewed in this study to determine the biological basis and current preclinical and clinical evidence for combination treatment of SBRT and immunotherapy
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