Immune Checkpoint Inhibitor Therapy Before Nephrectomy for Locally Advanced and Metastatic Renal Cell Carcinoma

Importance The therapeutic landscape of advanced renal cell carcinoma (RCC) has rapidly evolved in the past 2 decades, with the advent of cytokines therapy followed by targeted therapies and novel immune checkpoint inhibitors (ICI). This article aims to review the current evidence and ongoing trials of neoadjuvant or prenephrectomy ICI therapy in patients with locally advanced and metastatic RCC. Observations A literature search was performed using the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and PubMed as well as relevant medical society meetings for English-language studies, articles, and abstracts published before January 31, 2023. Currently, level I evidence supports the use of ICI-based combination therapy as the first-line treatment of patients with metastatic RCC with the potential option of deferred nephrectomy in those who respond to treatment. Nevertheless, limited prospective data are available regarding the role and outcomes of nephrectomy (cytoreductive or consolidative) in conjunction with ICI therapy in both metastatic and locally advanced RCC. Although data from retrospective case series confirmed the feasibility and safety of deferred nephrectomy in this setting, the sequence of nephrectomy and whether it should be considered in patients with metastatic RCC is a common clinical dilemma. However, although neoadjuvant targeted therapy for nonmetastatic RCCs has been associated with some advantages yet not accepted as a standard, current data from a phase 3 randomized clinical trial failed to demonstrate the oncologic benefit of neoadjuvant nivolumab for locally advanced RCC. Conclusion and Relevance The findings of this review suggest that ICI-based combination therapy is the standard of care as the first-line treatment of patients with metastatic RCC. However, the role of neoadjuvant ICIs in locally advanced RCC is an active area of investigation. Deferred nephrectomy after ICI-based immunotherapy for metastatic RCC is feasible and safe yet should be performed in high-volume health centers by experienced surgeons. The multidisciplinary and careful approach is critical for treatment decisions.