How can targeted therapy influence renal surgery for renal cell carcinoma?

Between the end of 2005 and the beginning of 2006 several new target therapies have been introduced for the treatment of renal cell carcinoma. In this review we aimed to explore and summarize the main findings about the use of systemic treatment and its effect on surgery in patients with renal cell carcinoma. We identified three different settings: neoadjuvant and adjuvant settings as well as the association of systemic therapy with surgery in the metastatic renal cell carcinoma patients. Neoadjuvant target therapy with tyrosine kinase inhibitor may facilitate the tumor resection and reduce the overall tumor diameter and its complexity. However, most of the evidences are from small phase I or II clinical trials and results are often conflicting without determining a relevant change in main parameters investigated, such as tumor complexity. In the adjuvant setting, results from pivotal trials investigating the use of tyrosine kinase inhibitor for patients with nonmetastatic RCC treated with surgery discourage this practice. Indeed, most of the evidences from single clinical trials and pooled results from meta-analysis failed to find a survival advantage with the use of adjuvant systemic treatment. To date, an improvement of clinical outcomes after systemic targeted therapies could be only found in the setting of cytoreductive nephrectomy. However, the CARMENA and SURTIME trials recently confirmed the evidences against a surgical treatment in patients with mRCC and poor prognosis. In the near future significant changes may be introduced by the use of immunotherapies.