Is Cytoreductive Nephrectomy Still Beneficial for Patients With Metastatic Renal Cell Carcinoma in the Contemporary Immunotherapy Era?

Abstract

Cytoreductive nephrectomy (CN) has long been the standard of care for patients with metastatic renal cell carcinoma (mRCC) since 2 clinical trials revealed its role during the cytokines era. With discovery of novel and effective drugs, such as vascular endothelial growth factor-targeted therapies, the role of CN started to be challenged. The 2 recent prospective randomized trials Cancer du Rein Metastatique Nephrectomie et Antiangiogéniques (CARMENA) and Immediate Surgery or Surgery After Sunitinib in Treating Patients with Metastatic Kidney Cancer trial (SURTIME) have changed the therapy paradigm for patients with mRCC. The CARMENA trial was performed to reveal whether CN is required in the targeted therapy, whereas SURTIME evaluated whether initial sunitinib can aid in the selection of patients who are most likely to benefit from subsequent CN or identify patients with innate resistance to targeted therapy. These trials suggest that CN does not provide a survival benefit for patients with poor‑risk disease. Especially, current evolutions in systemic therapies have demonstrated improved oncological outcomes from immunotherapy (IO) such as immune checkpoint inhibitor, particularly in its combination or combination with tyrosine kinase inhibitor. Accordingly, the role of CN continues to be questioned. Taken together, these findings reinforce the concept that the ultimate impact of CN on oncologic outcomes of mRCC patients in the era of IO still needs further investigation to represent a key for unmet clinical need.