Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2022 Jul;208(1):71-79.
doi: 10.1097/JU.0000000000002495. Epub 2022 Feb 25.

The Role of Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma: A Real-World Multi-Institutional Analysis

Pooja Ghatalia  1 , Elizabeth A Handorf  2 , Daniel M Geynisman  1 , Mengying Deng  2 , Matthew R Zibelman  1 , Philip Abbosh  3 , Fern Anari  1 , Richard E Greenberg  3 , Rosalia Viterbo  3 , David Chen  3 , Marc C Smaldone  3 , Alexander Kutikov  3 , Robert G Uzzo  3
Affiliations
Multicenter Study

The Role of Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma: A Real-World Multi-Institutional Analysis

Pooja Ghatalia et al. J Urol. 2022 Jul.

Abstract

Purpose: The role of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) was challenged by the results of the CARMENA trial. Here we evaluate the role of CN in mRCC patients, including those receiving modern therapies.

Materials and methods: We included patients with synchronous mRCC between 2011-2020 from the de-identified nationwide Flatiron Health database. We evaluated 3 groups: systemic therapy alone, CN followed by systemic therapy (up-front CN [uCN]) and systemic therapy followed by CN (deferred CN [dCN]). The primary outcome was median overall survival (mOS) in patients receiving systemic therapy alone vs uCN. Secondary outcome was overall survival in patients receiving uCN vs dCN. First-treatment, landmark and time-varying covariate analyses were conducted to overcome immortal time bias. Weighted Kaplan-Meier curves, log-rank tests and Cox proportional hazards regressions were used to assess the effect of therapy on survival.

Results: Of 1,910 patients with mRCC, 972 (57%) received systemic therapy, 605 (32%) received uCN, 142 (8%) dCN and 191 (10%) CN alone; 433 (23%) patients received immunotherapy-based therapy. The adjusted mOS was significantly improved in first-treatment, landmark and time-varying covariate analysis (mOS 26.6 vs 14.6 months, 36.3 vs 21.1 months and 26.1 vs 12.2 months, respectively) in patients undergoing CN. Among patients receiving CN and systemic therapy, the timing of systemic therapy relative to CN was not significantly related to overall survival (HR=1.0, 95% CI 0.76-1.32, p=0.99).

Conclusions: Our findings support an oncologic role for CN in select mRCC patients. In patients receiving both CN and systemic therapy, the survival benefit compared to systemic alone was similar for up-front and deferred CN.

Keywords: carcinoma, renal cell; nephrectomy; surgery.

PubMed Disclaimer

Figures

Figure 1:
Figure 1:. Consort diagram
CN: Cytoreductive nephrectomy; IO: immunotherapy; TT: targeted therapy (includes tyrosine kinase inhibitors (TKI) and mammalian target of rapamycin (mTOR) inhibitors); tx: treatment; uCN: CN followed by systemic therapy; dCN: systemic therapy followed by CN
Figure 2:
Figure 2:. Adjusted Kaplan Meier Overall Survival (OS) in all patients using sensitivity analysis
The sensitivity analysis incorporates all patients – those who receive CN alone, CN followed by systemic therapy, systemic therapy followed by CN and systemic therapy alone. Patients were categorized based on the treatment they received first- CN or systemic therapy; CN: cytoreductive nephrectomy
Figure 3:
Figure 3:. Adjusted Kaplan Meier Overall Survival (OS) in all patients using 6-month landmark
We conducted a landmark analysis with the landmark set at 6 months (i.e. analyzing only patients who survived to 6 months), with the landmark time chosen based on our inclusion criteria. uCN: upfront CN followed by systemic therapy; dCN: systemic therapy followed by deferred CN
See this image and copyright information in PMC

Comment in

References

    1. Heng DY, Xie W, Regan MM, et al. Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol. Dec 2009;27(34):5794–5799. - PubMed
    1. Motzer RJ, Mazumdar M, Bacik J, Berg W, Amsterdam A, Ferrara J. Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol. Aug 1999;17(8):2530–2540. - PubMed
    1. Flanigan RC, Mickisch G, Sylvester R, Tangen C, Van Poppel H, Crawford ED. Cytoreductive nephrectomy in patients with metastatic renal cancer: a combined analysis. J Urol. Mar 2004;171(3):1071–1076. - PubMed
    1. Mickisch GH, Garin A, van Poppel H, de Prijck L, Sylvester R, Group EOfRaToCEG. Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial. Lancet. Sep 2001;358(9286):966–970. - PubMed
    1. Mejean A, Ravaud A, Thezenas S, et al. Sunitinib Alone or after Nephrectomy in Metastatic Renal-Cell Carcinoma. N Engl J Med. Aug 2 2018;379(5):417–427. - PubMed

Publication types

MeSH terms