Preoperative tyrosine kinase inhibition as an adjunct to debulking nephrectomy

OBJECTIVES Since the introduction of tyrosine kinase inhibitors (TKI), treatment of metastatic renal cell carcinoma (RCC) has undergone dramatic changes. However, the use of TKI therapy in adjunctive settings remains to be defined. We present a single-institution experience of patients who received preoperative TKI before nephrectomy for metastatic or unresectable disease. METHODS The records of 9 patients with locally advanced or metastatic RCC treated with TKI therapy before nephrectomy at the University of North Carolina were reviewed. All procedures and radiographic images were performed at I institution. The cases were surveyed for the effect of TKI on tumor burden and surgical approach and timing. RESULTS The patients received systemic therapy with either sorafenib or sunitinib before proceeding to nephrectomy on clinical trials for metastatic disease or as the standard of care, The surgery was well tolerated by all patients, without an apparent effect from TKI therapy on the surgical technique or complications. Responses were observed in the primary tumor, as well as in the metastatic sites. CONCLUSIONS Neoadjuvant TKI therapy can induce responses in the primary tumor and has the potential advantage of cytoreduction when administered before nephrectomy for RCC. This setting also potentially provides an opportunity to evaluate the TKI responsiveness of patients with metastatic disease. However, prospective trials evaluating adjunctive surgical approaches to locally advanced and metastatic RCC are needed to determine the significant benefits of TKI therapy and to define the optimal agent, timing of therapy, and disease stage to derive benefit for preoperative therapy.