Upfront Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors or Targeted Therapy: An Observational Study from the International Metastatic Renal Cell Carcinoma Database Consortium

Ziad Bakouny; Talal El Zarif; Shaan Dudani; J Connor Wells; Chun Loo Gan; Frede Donskov; Julia Shapiro; Ian D Davis; Francis Parnis; Praful Ravi; John A Steinharter; Neeraj Agarwal; Ajjai Alva; Lori Wood; Anil Kapoor; Jose M Ruiz Morales; Christian Kollmannsberger; Benoit Beuselinck; Wanling Xie; Daniel Y C Heng; Toni K Choueiri

doi:10.1016/j.eururo.2022.10.004

Upfront Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors or Targeted Therapy: An Observational Study from the International Metastatic Renal Cell Carcinoma Database Consortium

Eur Urol. 2023 Feb;83(2):145-151. doi: 10.1016/j.eururo.2022.10.004. Epub 2022 Oct 20.

Authors

Ziad Bakouny¹, Talal El Zarif², Shaan Dudani³, J Connor Wells⁴, Chun Loo Gan⁵, Frede Donskov⁶, Julia Shapiro⁷, Ian D Davis⁸, Francis Parnis⁹, Praful Ravi², John A Steinharter¹⁰, Neeraj Agarwal¹¹, Ajjai Alva¹², Lori Wood¹³, Anil Kapoor¹⁴, Jose M Ruiz Morales¹⁵, Christian Kollmannsberger¹⁶, Benoit Beuselinck¹⁷, Wanling Xie¹⁸, Daniel Y C Heng⁴, Toni K Choueiri¹⁹

Affiliations

¹ Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
² Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
³ Department of Oncology, William Osler Health System, Brampton, ON, Canada.
⁴ Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada.
⁵ Royal Melbourne Hospital, Melbourne, Australia.
⁶ Department of Oncology, Aarhus University Hospital, Aarhus, Denmark; University Hospital of Southern Denmark, Esbjerg, Denmark.
⁷ Cabrini Hospital, Malvern, Australia.
⁸ Monash University Eastern Health Clinical School, Melbourne, Australia; Cancer Services, Eastern Health, Melbourne, Australia.
⁹ delaide Cancer Centre, Adelaide, Australia.
¹⁰ Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
¹¹ Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT, USA.
¹² University of Michigan, Ann Arbor, MI, USA.
¹³ Dalhousie University, Halifax, NS, Canada.
¹⁴ Juravinski Cancer Centre, McMaster University, Hamilton, ON, Canada.
¹⁵ Hospital Medica Sur, Mexico City, Mexico.
¹⁶ BC Cancer-Vancouver Centre, Vancouver, BC, Canada.
¹⁷ University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium.
¹⁸ Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA, USA.
¹⁹ Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: Toni_Choueiri@dfci.harvard.edu.

PMID: 36272943
DOI: 10.1016/j.eururo.2022.10.004

Abstract

Background: The role of upfront cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) in the era of immune checkpoint inhibitors is unclear.

Objective: To evaluate the relationship between upfront CN and clinical outcomes in the setting of mRCC treated with immune checkpoint inhibitors or targeted therapy.

Design, setting, and participants: Using the International Metastatic RCC Database Consortium, we retrospectively identified patients diagnosed with de novo mRCC treated with immune checkpoint inhibitors or targeted therapy.

Outcome measurements and statistical analysis: Overall survival (OS) was compared between the two groups using the Kaplan-Meier method and multivariable Cox regressions adjusting for known prognostic factors.

Results and limitations: We identified a total of 4639 eligible patients with mRCC. Among the 4202 patients treated with targeted therapy and 437 patients treated with immune checkpoint inhibitors, 2326 (55%) and 234 (54%) patients received upfront CN prior to treatment start. In multivariable analyses, CN was associated with significantly better OS in both the immune checkpoint inhibitor-treated (hazard ratio [HR]: 0.61; 95% confidence interval [CI], 0.41-0.90, p = 0.013) and the targeted therapy treatment (HR: 0.72; 95% CI, 0.67-0.78, p < 0.001) group. There was no difference in OS benefit of CN between the immune checkpoint inhibitor and targeted therapy treatment groups (interaction p = 0.6). Limitations include selection of patients from large academic centers and the retrospective nature of the study.

Conclusions: Upfront CN is associated with a significant OS benefit in selected patients treated by either immune checkpoint inhibitors or targeted therapy, and still has a role in selected patients in the era of immune checkpoint inhibitors.

Patient summary: Before effective systemic therapies were available for metastatic kidney cancer, surgical removal of the primary (kidney) tumor was the mainstay of treatment. The role of removing the primary tumor has recently been called into question given that more effective systemic therapies have become available. In this study, we find that removal of the primary kidney tumor still has a benefit for selected patients treated with highly effective modern systemic therapies, including targeted therapies and immune checkpoint inhibitors.

Keywords: Cytoreductive nephrectomy; Immune checkpoint inhibitors; Renal cell carcinoma; Targeted therapy.

Publication types

Observational Study

MeSH terms

Carcinoma, Renal Cell* / drug therapy
Carcinoma, Renal Cell* / surgery
Cytoreduction Surgical Procedures / methods
Humans
Immune Checkpoint Inhibitors / therapeutic use
Kidney Neoplasms* / drug therapy
Kidney Neoplasms* / surgery
Nephrectomy / methods
Retrospective Studies

Substances

Immune Checkpoint Inhibitors