Cytoreductive nephrectomy in metastatic kidney cancer: what do we do now?

Metastatic renal cell carcinoma (mRCC) has traditionally been treated with a combination of targeted systemic therapy and cytoreductive nephrectomy. This approach has recently become a topic of debate, because of new randomized data suggesting a lack of survival benefit for cytoreductive nephrectomy. We review the literature relevant to cytoreductive nephrectomy in the modern era of targeted and immune systemic therapy, and discuss the ongoing role of surgery for treatment of patients with mRCC.

Randomized trials in the cytokine era of systemic therapy for mRCC demonstrated a survival benefit to cytoreductive nephrectomy, which led to its widespread adoption. There is overwhelming support in favor of cytoreductive nephrectomy from large studies using retrospective data in the targeted therapy era. A recent randomized control trial (CARMENA) failed to show superiority of cytoreductive nephrectomy in combination with sunitinib, versus sunitinib alone with respect to overall survival. The trial had major limitations including selection of many poor-risk patients, which we know do not benefit from surgery. The results of CARMENA should lead to the abandonment of cytoreductive nephrectomy in poor-risk and many intermediate-risk patients with mRCC. However, there is a knowledge gap with respect to the role of cytoreductive nephrectomy in patients with good risk disease, and we argue that these patients should be strongly considered for cytoreductive nephrectomy.

Cytoreductive nephrectomy continues to play an important role in the multidisciplinary management of mRCC; however, diligent patient selection is crucial, as only patients with good risk features are likely to derive benefit from surgery.