The role of neoadjuvant therapy in the management of locally advanced renal cell carcinoma

Abstract

Abstract:In the past decade, the armamentarium of targeted therapy agents for the treatment of metastatic renal cell carcinoma (RCC) has significantly increased. Improvements in response rates and survival, with more manageable side effects compared with interleukin 2/interferon immunotherapy, have been reported with the use of targeted therapy agents, including vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors (sunitinib, sorafenib, pazopanib, axitinib), mammalian target of rapamycin (mTOR) inhibitors (everolimus and temsirolimus) and VEGF receptor antibodies (bevacizumab). Current guidelines reflect these new therapeutic approaches with treatments based on risk category, histology and line of therapy in the metastatic setting. However, while radical nephrectomy remains the standard of care for locally advanced RCC, the migration and use of these agents from salvage to the neoadjuvant setting for large unresectable masses, high-level venous tumor thrombus involvement, and patients with imperative indications for nephron sparing has been increasingly described in the literature. Several trials have recently been published and some are still recruiting patients in the neoadjuvant setting. While the results of these trials will inform and guide the use of these agents in the neoadjuvant setting, there still remains a considerable lack of consensus in the literature regarding the effectiveness, safety and clinical utility of neoadjuvant therapy. The goal of this review is to shed light on the current body of evidence with regards to the use of neoadjuvant treatments in the setting of locally advanced RCC.

Sunitinib or Sorafenib as Neoadjuvant Therapy May not Improve the Survival Outcomes of Renal Cell Carcinoma with Tumor Thrombus

“…Neoadjuvant target therapy may also lead to disease progression and make some patients suffer from adverse effects [22]. In our study, we found that neoadjuvant targeted therapy was safe for RCC patients in terms of side effects and surgeries.…”

“…The effectiveness of neoadjuvant therapy in reducing tumor size [19] and reducing tumor complexity [20] was proved. However, the therapeutic effect of neoadjuvant therapy on RCC patients with tumor thrombus is still controversial and neoadjuvant therapy might be less encouraged for RCC patients with tumor thrombus [21,22], while no study investigated whether neoadjuvant therapy could increase the survival outcomes for RCC patients with tumor thrombus so far. Thus, this work is the first research which focuses on survival benefits of neoadjuvant therapy to explore the value of it.…”

“…The target popu- lation for neoadjuvant therapy was those with local RCC or locally advanced non-metastatic RCC and for pseudo-neoadjuvant therapy was those with advanced mRCC [22]. And this study only included those with non-mRCC with tumor thrombus who have undergone surgery to investigate the effect of neoadjuvant therapy on this population.…”

A Prospective Multicenter Trial of the Efficacy and Tolerability of Neoadjuvant Sunitinib for Inoperable Metastatic Renal Cell Carcinoma

“…However, during the current era of TT, NT strategies have regained the attention of oncologists, and several trials of NT for RCC and mRCC have recently been completed or are ongoing (567). Some trials have established the safety and response rates of NT with several agents, but there is no consensus in the literature regarding the effectiveness, safety, and clinical utility of NT (8). Therefore, the possible or conceivable indications for neoadjuvant TT now include the treatment of 1) large unresectable advanced tumors to facilitate surgery, 2) imperative indications to enable a nephron-sparing procedure, and 3) high-level vena cava thrombi involvement to achieve downsizing and facilitate the use of simpler surgical techniques that are associated with lower morbidity rates.…”

Prognostic Benefit of Surgical Management of Renal Cell Carcinoma Invading the Inferior Vena Cava

“…Current evidence in the literature demonstrates the potentially expanding role of preoperative targeted therapy with tyrosine kinase inhibitors in the management of locally advanced RCC [31]. Traditionally, systemic therapy has shown limited usefulness, and aggressive radical surgical resection with IVC thrombectomy remains the standard of care in appropriate candidates.…”