Deferred Cytoreductive Nephrectomy in Patients with Newly Diagnosed Metastatic Renal Cell Carcinoma

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  • Bimal Bhindi, University of Calgary
  • ,
  • Jeffrey Graham, CancerCare Manitoba
  • ,
  • J Connor Wells, University of Calgary
  • ,
  • Ziad Bakouny, Harvard Medical School
  • ,
  • Frede Donskov
  • Anna Fraccon, CDC Pererzoli, Peschiera del Garda, Italy.
  • ,
  • Felice Pasini, Ospedale Santa Maria della Misericordia
  • ,
  • Jae Lyun Lee, University of Ulsan
  • ,
  • Naveen S Basappa, University of Alberta
  • ,
  • Aaron Hansen, Princess Margaret Cancer Centre
  • ,
  • Christian K Kollmannsberger, British Columbia Cancer Agency
  • ,
  • Ravindran Kanesvaran, National Cancer Centre Singapore
  • ,
  • Takeshi Yuasa, Cancer Institute Hospital of Japanese Foundation for Cancer Research
  • ,
  • D Scott Ernst, Western University
  • ,
  • Sandy Srinivas, Stanford Medical Center
  • ,
  • Brian I Rini, Taussig Cancer Institute
  • ,
  • Isaac Bowman, UT Southwestern Medical Center, Dallas, TX
  • ,
  • Sumanta K Pal, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
  • ,
  • Toni K Choueiri, Harvard Medical School
  • ,
  • Daniel Y C Heng, University of Calgary

BACKGROUND: The use of cytoreductive nephrectomy (CN) selectively for patients who show a favorable response to upfront systemic therapy may be an approach to select optimal candidates with metastatic renal cell carcinoma (mRCC) who are most likely to benefit.

OBJECTIVE: We sought to characterize outcomes of deferred CN (dCN) after upfront sunitinib, outcomes relative to sunitinib alone, and outcomes of CN followed by sunitinib.

DESIGN, SETTING, AND PARTICIPANTS: We used the prospectively maintained International mRCC Database Consortium (IMDC) database to identify patients with newly diagnosed mRCC (2006-2018).

INTERVENTION: Sunitinib alone, upfront CN followed by sunitinib, sunitinib followed by dCN.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcomes were overall survival (OS) and time to sunitinib treatment failure (TTF). Kaplan-Meier and multivariable Cox regression analyses were performed; dCN was analyzed as a time-varying covariate to account for immortal time bias.

RESULTS AND LIMITATIONS: We evaluated 1541 patients, of whom 651 (42%) received sunitinib alone, 805 (52%) underwent CN followed by sunitinib, and 85 (5.5%) received sunitinib followed by dCN, at a median of 7.8 mo from diagnosis. Median OS periods for patients treated with sunitinib alone, CN followed by sunitinib, and sunitinib followed by dCN were 10, 19, and 46 mo, respectively, while the median TTF values were 4, 8, and 13 mo, respectively. In multivariable regression analyses, sunitinib followed by dCN was significantly associated with improved OS (hazard ratio [HR] = 0.45, 95% confidence interval [CI] 0.33-0.60, p < 0.001) and TTF (HR = 0.62, 95% CI 0.46-0.85, p = 0.003) versus sunitinib alone. Among CN-treated patients, sunitinib followed by dCN was associated with improved OS (HR = 0.52, 95% CI 0.39-0.70, p < 0.001) and TTF (HR = 0.71, 95% CI 0.56-0.90, p = 0.005) compared with upfront CN followed by sunitinib. In various sensitivity analyses, dCN remained significantly associated with improved OS and TTF.

CONCLUSIONS: Patients who received dCN were carefully selected and achieved long OS. With these benchmark outcomes, optimal selection criteria need to be identified and confirmation of the role of dCN in a clinical trial is warranted.

PATIENT SUMMARY: We characterized benchmark survival outcomes for patients with metastatic kidney cancer treated with sunitinib alone, nephrectomy (kidney removal) followed by sunitinib, and sunitinib followed by nephrectomy. Patients who had their nephrectomy after an initial course of sunitinib had prolonged survival.

Original languageEnglish
JournalEuropean Urology
Volume78
Issue4
Pages (from-to)615-623
Number of pages9
ISSN1828-6569
DOIs
Publication statusPublished - 2020

    Research areas

  • Cytoreduction surgical procedures, Neoplasm metastasis, Nephrectomy, Renal cell carcinoma, Targeted therapy, Tyrosine kinase inhibitor

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