Adjuvant and neoadjuvant therapy in renal cell carcinoma

A number of patients with renal cell carcinoma (RCC) are faced with the knowledge that, despite undergoing nephrectomy, they have a substantial risk of disease recurrence. Prior efforts to decrease recurrence risk using immunotherapy have largely been ineffective. The reasons for the failure of immunotherapy are not clear, as our ability to measure immunological outcomes has not provided us with clues on the determinants which signal a successful antitumor effect. We are now entering the targeted therapy era, and clinical trials are underway to determine whether adjuvant or neoadjuvant targeted therapy strategies are helpful in higher risk patients. Once again, we are faced with a paucity of surrogate markets of success or failure in treating micrometastatic disease, and the absence of a clear understanding of the biology of these agents in the adjuvant setting. As trial information becomes available we will be able to form hypotheses based on clinical observations. In the meantime, it is important that we in parallel develop a conceptual framework that Will prepare us to address the questions that will inevitably arise from our experience with these agents. Additional questions arise about timing or therapy in the high risk setting. If an effective treatment exists, should it be given before or after nephrectomy? Potential strategies to answer these questions are outlined in the manuscript.