Deferred Cytoreductive Nephrectomy Following Presurgical Vascular Endothelial Growth Factor Receptor-targeted Therapy in Patients with Primary Metastatic Clear Cell Renal Cell Carcinoma: A Pooled Analysis of Prospective Trial Data

Eur Urol Oncol. 2020 Apr;3(2):168-173. doi: 10.1016/j.euo.2019.12.004. Epub 2020 Jan 16.


Background: Cancer du Rein Métastatique Nephrectomie et Antiangiogéniques (CARMENA) concluded that sunitinib alone is not inferior to cytoreductive nephrectomy (CN) followed by vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) in patients with metastatic renal cell carcinoma. It remains uncertain whether deferred CN is beneficial in this setting.

Objective: The aim of this study was to compare outcome in patients treated with presurgical VEGFR-TKI followed by CN (deferred CN) with that in patients receiving CN followed by VEGFR-TKI (upfront CN).

Design, setting, and participants: Pooled data from prospective trials in which a strategy of deferred CN in the absence of disease progression was investigated were compared with a retrospective dataset of upfront CN.

Outcome measurements and statistical analysis: Overall survival (OS) in the Memorial Sloan-Kettering Cancer Center (MSKCC) intermediate-risk group.

Results and limitations: Patients were treated between 2006 and 2016. In the MSKCC intermediate-risk group, 144 patients with a strategy of deferred CN after systemic therapy were compared with 131 patients treated with upfront CN. OS in the deferred cohort was 33.0 mo (95% confidence interval [CI] 25.0-51.0) compared with 22.8 mo (95% CI 17.9-30.6) after upfront CN (hazard ratio 0.72 [95% CI 0.52-0.996], p = 0.047). This study is limited by retrospective comparison of data, subgroup analysis, and a lack of intention-to-treat data for the upfront CN cohort.

Conclusions: In MSKCC intermediate-risk patients, a strategy of deferred CN in the absence of progression yields OS, which compares favourably with upfront CN and published trial data from CARMENA. This warrants a formal individual patient data analysis of CARMENA, SURTIME, and single-arm prospective studies to define the role and timing of deferred CN in intermediate-risk patients.

Patient summary: In this study, we report outcomes in patients with metastatic renal cell cancer treated with targeted therapy followed by nephrectomy, which compared favourably with nephrectomy followed by targeted therapy and results from published studies.

Keywords: Cytoreductive nephrectomy; Renal cell carcinoma; Vascular endothelial growth factor receptor tyrosine kinase inhibitor.

MeSH terms

  • Carcinoma, Renal Cell / drug therapy*
  • Cytoreduction Surgical Procedures / methods*
  • Female
  • Humans
  • Kidney Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Nephrectomy / methods*
  • Prospective Studies
  • Retrospective Studies
  • Vascular Endothelial Growth Factor A / therapeutic use*


  • Vascular Endothelial Growth Factor A