Evolving biological associations of upfront cytoreductive nephrectomy in metastatic renal cell carcinoma

Andrew W. Silagy, Ritesh R. Kotecha, Stanley Weng, Arturo Holmes, Nirmish Singla, Roy Mano, Kyrollis Attalla, Kate L. Weiss, Renzo G. DiNatale, Sujata Patil, Jonathan A. Coleman, Robert J. Motzer, Paul Russo, Martin H. Voss, A. Ari Hakimi

Research output: Contribution to journalArticlepeer-review


Background: Systemic responses to cytoreductive nephrectomy (CN) in the management of metastatic renal cell carcinoma (mRCC) are variable and difficult to anticipate. The authors aimed to determine the association of CN with modifiable International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factors and oncological outcomes. Methods: Consecutive patients with mRCC referred for potential CN (2009-2019) were reviewed. The primary outcome was overall survival (OS); variables of interest included undergoing CN and the baseline number of modifiable IMDC risk factors (anemia, hypercalcemia, neutrophilia, thrombocytosis, and reduced performance status). For operative cases, the authors evaluated the effects of IMDC risk factor dynamics, measured 6 weeks and 6 months after CN, on OS and postoperative treatment disposition. Results: Of 245 treatment-naive patients with mRCC referred for CN, 177 (72%) proceeded to surgery. The CN cases had fewer modifiable IMDC risk factors (P =.003), including none in 71 of 177 patients (40.1%); fewer metastases (P =.011); and higher proportions of clear cell histology (P =.012). In a multivariable analysis, surgical selection, number of IMDC risk factors, metastatic focality, and histology were associated with OS. Total risk factors changed for 53.8% and 57.2% of the patients from the preoperative period to 6 weeks and 6 months after CN, respectively. Adjusted for preoperative IMDC risk scores, an increase in IMDC risk factors at 6 weeks and 6 months was associated with adverse OS (hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.13-2.19; P =.007; HR, 2.52; 95% CI, 1.74-3.65; P <.001). Conclusions: IMDC risk factors are dynamic clinical variables that can improve after upfront CN in select patients, and this suggests a systemic benefit of cytoreduction, which may confer clinically meaningful prognostic implications.

Original languageEnglish (US)
Pages (from-to)3946-3956
Number of pages11
Issue number21
StatePublished - Nov 1 2021
Externally publishedYes


  • cytoreductive nephrectomy
  • patient selection
  • renal cell carcinoma
  • risk stratification

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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