Introduction: Recently, immune checkpoint inhibitor (ICI)-combination therapies have radically altered the treatment landscape in metastatic renal cell carcinoma (mRCC). No phase 3 trials have assessed the impact of cytoreductive nephrectomy (CN) for efficacy in mRCC patients treated with ICI-combination therapy. Thus, we assessed the role of CN in mRCC patients in the ICI-combination therapy era.
Methods: Multiple databases were searched for articles published until October 2021. Studies comparing overall survival (OS) and/or progression-free survival (PFS) in mRCC patients treated with ICI combination-therapy as first-line were deemed eligible.
Results: Six studies met the eligibility criteria. ICI-combination therapy was associated with significantly better OS/PFS than sunitinib in patients who had undergone CN (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.59–0.77/HR, 0.57; 95% CI, 0.44–0.74, respectively; both P<0.001), and in those who had not (HR, 0.69; 95% CI, 0.57–0.85/ HR, 0.63; 95% CI, 0.52–0.77, respectively; both P<0.001). Although the OS and PFS benefits of ICI-combination therapy were larger in those undergoing CN, the HR for OS and PFS indicated that ICI-combination therapy’s treatment effect did not differ substantially with or without CN. In network meta-analyses, nivolumab plus cabozantinib was the most effective regimen in those undergoing CN, and pembrolizumab plus lenvatinib for those not undergoing CN.
Conclusions: CN offers limited survival benefits to mRCC patients receiving ICI-combination therapy. Careful patient selection remains paramount. As each ICI-combination regimen varied widely in its effect in those who had and had not undergone CN, CN may contribute to better treatment decision-making for ICI combination therapy recipients.
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