Neoadjuvant (presurgical) therapy for renal cell carcinoma: A new treatment paradigm for locally advanced and metastatic disease

BACKGROUND: Although upfront cytoreductive nephrectomy followed by systemic therapy remains the standard of care for metastatic renal cell carcinoma, the addition of novel targeted therapy has prompted a reevaluation of this treatment paradigm. The authors reviewed their experience with neoadjuvant systemic therapy administered before cytoreductive surgery for metastatic, locally recurrent, or regionally advanced renal cell carcinoma. METHODS: The authors compared patients treated with presurgical targeted therapy (with sunitinib, sorafenib, or bevacizumab) with a contemporary group that underwent up-front cytoreductive surgery. RESULTS: The authors found no difference in any perioperative surgical parameters indicative of morbidity or mortality between the 2 groups. Laboratory models of renal cell carcinoma treated with systemic targeted therapy demonstrate specific protein expression profiles that correlate with response to therapy and the development of therapy resistance. CONCLUSIONS: Neoadjuvant (presurgical) targeted therapy before cytoreductive surgery appears safe in the setting of metastatic renal cell carcinoma. It identifies patients who respond to systemic therapy before surgery, thus avoiding highly morbid surgery in patients destined for a poor outcome. Further studies are needed to identify the molecular endpoints associated with treatment response and the development of the resistant phenotype, which will in turn identify novel transduction pathways worthy of therapeutic development.