To combine or not combine: the role of radiotherapy and targeted agents in the treatment for renal cell carcinoma.

introductionRenal cell carcinoma is counted among the most resistant tumors to chemotherapy and radiotherapy, respectively. However, therapeutic options expanded since the introduction of molecular agents, targeting specific pathways such as the vascular endothelial growth factor (VEGF)-α, the VEGF receptor (VEGFR), or the mammalian target of rapamycin (mTOR) pathway. These new agents almost doubled the time to tumor progression and in some trials even improved overall survival. Against this background, the role of local treatment strategies in metastasized or inoperable primary renal cell carcinoma has to be redefined. With the onset of new technical developments in radiotherapy and the possibility to precisely deliver higher doses per fraction, encouraging response and control rates have been reported for kidney cancer, supporting a possible role for irradiation in this setting. This overview summarizes the preclinical data and clinical experiences of modern radiotherapy with focus on possible synergies and toxicities when combined with molecular targeted agents.

methodsThe available literature on preclinical and clinical data comprising prospective trials, retrospective analyses and case reports was reviewed.

conclusionWith the recent developments in stereotactic and image-guided radiotherapy, encouraging data concerning local control in the treatment for metastasized renal cell carcinoma have been generated and are therefore recommended whenever possible. It seems that with these high- precision irradiation schedules, the combination with targeted agents is feasible with no increase in severe adverse events. Nevertheless, the addition of molecular targeted drugs to radiotherapy outside of approved regimens or clinical trials warrants careful consideration for every single case.