In the cytokine era, 2 randomized clinical trials^1,2 have shown a modest but statistically significant survival benefit of cytoreductive nephrectomy (CN) followed by interferon alfa vs interferon alfa alone in patients with primary metastatic renal cancer (mRCC). A combined analysis³ of both studies demonstrated a significant median overall survival (OS) improvement of 5.8 months with CN and interferon compared with interferon alone. Since 2006, more effective vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) have been the standard of care for the treatment of mRCC.⁴ Guidelines recommend CN in patients with good performance, absence of poor risk features, and solitary or oligometastatic disease,^5-7 but the role of CN for patients who require medical treatment in the targeted therapy era is unknown. Although multiple retrospective studies have reported a survival benefit with CN in combination with VEGFR-TKIs,⁷ results were biased, and surgery-related morbidity may prevent delivering postoperative systemic therapy.^8,9 The Clinical Trial to Assess the Importance of Nephrectomy (CARMENA), a trial designed to answer the question of whether CN is still required in the era of targeted therapy in patients with primary mRCC, aimed to demonstrate noninferior survival with sunitinib alone compared with CN followed by sunitinib.¹⁰ Parallel to CARMENA, the European Organisation for Research and Treatment of Cancer (EORTC) GenitoUrinary Cancer Group, the National Cancer Research Institute Renal Clinical Studies Group/Wales Cancer Trial Unit (United Kingdom), and the Canadian Uro-Oncology Group jointly conducted the Immediate Surgery or Surgery After Sunitinib Malate in Treating Patients With Metastatic Kidney Cancer (SURTIME) trial, a randomized clinical trial of immediate vs deferred CN in patients with synchronous mRCC treated with sunitinib. The objective of SURTIME was to investigate whether pretreatment before planned surgery improves outcome by identifying patients with inherent resistance to VEGFR-TKIs who are unlikely to benefit from CN. Prior single-arm phase 2 studies^11,12 of deferred CN after presurgical sunitinib demonstrated that the approach is safe and avoids CN in individuals with early resistance to VEGFR-TKIs while exposing patients with aggressive disease to immediate systemic therapy. In addition, a deferred approach may reduce cancer-related morbidity, primary tumor size, and neovascularization, which in turn may decrease surgical risk and morbidity.^13,14