Deferred cytoreductive nephrectomy in the management of metastatic renal cell carcinoma: A systematic review and meta-analysis

Deferred cytoreductive nephrectomy (dCN) after upfront systemic therapy has been utilized in the management of select patients with metastatic renal cell carcinoma (mRCC). Herein, we sought to review the current evidence and define oncologic and perioperative outcomes associated with deferred surgical management of newly diagnosed mRCC. Our objective was to critically evaluate the role of dCN in the targeted and immunotherapy eras, comparing oncologic and perioperative outcomes between dCN and upfront CN. Medline, OVID, and Scopus databases were searched for studies evaluating patients undergoing dCN following systemic therapy (ST). PRISMA guidelines were referenced and followed. Outcomes of interest included overall survival (OS), progression free survival (PFS), percent of patients proceeding to dCN, reduction in primary tumor size, complication rates, and perioperative mortality. Random effects meta-analysis was performed comparing overall survival between dCN vs. ST alone and dCN vs. upfront CN. Nineteen studies were included to assess the primary outcomes. The percent of patients proceeding to planned dCN after planned pre-surgical ST ranged from 60.5% to 84%. The most common reason for not undergoing dCN was disease progression on upfront ST. Of patients undergoing dCN, 76% to 96% were able to resume ST postoperatively. OS and PFS ranged from 12.4 to 46 months and 4.5 to 11 months, respectively. Pooled results demonstrated significantly improved OS favoring dCN over upfront CN (hazard ratio, HR = 0.56; 95% CI 0.45–0.69) and ST alone (HR = 0.45; 95% CI 0.38–0.53). Deferred CN represents a potential treatment option in appropriately selected patients with mRCC with a favorable response to upfront systemic therapy. Future randomized trials will be needed to clarify how much this is due to the surgery vs. patient selection.