Systematic Review: Perioperative Systemic Therapy for Metastatic Renal Cell Carcinoma

Abstract

Background: Approximately 16% of patients with renal cell carcinomas (RCC) present with stage IV disease at time of diagnosis. Treatment options for metastatic clear cell RCC, the most common histologic subtype, have proliferated over the past decade and include a combination of surgery and systemic therapy. The selection of systemic agent and best timing of systemic therapy in relation to nephrectomy is an area of active research. Objective: To evaluate the evidence for perioperative systemic therapy, including presurgical and postsurgical, for metastatic RCC. Methods: A systematic literature search using PubMed and MEDLINE databases was performed in January 2017 for articles related to perioperative systemic therapy in metastatic RCC using key word search terms. The authors screened the search results and identified selected publications by predetermined inclusion criteria and consensus. Expert opinion was obtained to assess for publications missed by search. Results: Early phase clinical trials of antiangiogenic tyrosine kinase inhibitors prior to cytoreductive nephrectomy in select patients show that these systemic agents are safe and effective in the presurgical setting. There are no randomized data evaluating pre- or post-surgical systemic therapy in metastatic RCC. Conclusions: Retrospective and early-phase prospective studies on the use and timing of systemic therapy in relation to cytoreductive nephrectomy in metastatic RCC show that standard of care antiangiogenic agents are safe and effective in the perioperative setting, though randomized data are still lacking. Pre-surgical immune checkpoint therapy for metastatic RCC has strong biologic rationale and holds promise. Sequential tumor sampling in neoadjuvant and presurgical trials is necessary to determine biomarkers of response and resistance.

Keywords: RCC; Renal cell carcinoma; immune therapy; nephrectomy; presurgical therapy; toxicity.

Fig.1

Schematic of early-phase clinical trial for presurgical systemic antiangiogenic therapy in metastatic RCC. Sequential tissue acquisition pre and post systemic therapy allows for identification of biologic drivers of cancer progression as well as predictive and prognostic biomarker development.