Characterization of Patients with Metastatic Renal Cell Carcinoma Undergoing Deferred, Upfront, or No Cytoreductive Nephrectomy in the Era of Combination Immunotherapy: Results from the International Metastatic Renal Cell Carcinoma Database Consortium

Kosuke Takemura; Matthew S Ernst; Vishal Navani; J Connor Wells; Ziad Bakouny; Frede Donskov; Naveen S Basappa; Lori A Wood; Luis Meza; Sumanta K Pal; Bernadett Szabados; Thomas Powles; Benoit Beuselinck; Rana R McKay; Jae-Lyun Lee; D Scott Ernst; Anil Kapoor; Takeshi Yuasa; Toni K Choueiri; Daniel Y C Heng

doi:10.1016/j.euo.2023.10.002

Characterization of Patients with Metastatic Renal Cell Carcinoma Undergoing Deferred, Upfront, or No Cytoreductive Nephrectomy in the Era of Combination Immunotherapy: Results from the International Metastatic Renal Cell Carcinoma Database Consortium

Eur Urol Oncol. 2023 Oct 30:S2588-9311(23)00217-1. doi: 10.1016/j.euo.2023.10.002. Online ahead of print.

Authors

Kosuke Takemura¹, Matthew S Ernst², Vishal Navani², J Connor Wells³, Ziad Bakouny⁴, Frede Donskov⁵, Naveen S Basappa⁶, Lori A Wood⁷, Luis Meza⁸, Sumanta K Pal⁸, Bernadett Szabados⁹, Thomas Powles⁹, Benoit Beuselinck¹⁰, Rana R McKay¹¹, Jae-Lyun Lee¹², D Scott Ernst¹³, Anil Kapoor¹⁴, Takeshi Yuasa¹⁵, Toni K Choueiri⁴, Daniel Y C Heng²

Affiliations

¹ Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada; Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan. Electronic address: kosuke.takemura@albertahealthservices.ca.
² Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada.
³ BC Cancer Agency, Vancouver, BC, Canada.
⁴ Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
⁵ Aarhus University Hospital, Aarhus, Denmark; University Hospital of Southern Denmark, Esbjerg, Denmark.
⁶ Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada.
⁷ Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, NS, Canada.
⁸ City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
⁹ Barts Cancer Institute, Queen Mary University of London, London, UK.
¹⁰ Leuven Cancer Institute, KU Leuven, Leuven, Belgium.
¹¹ Moores Cancer Center, University of California San Diego, La Jolla, CA, USA.
¹² Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
¹³ London Regional Cancer Program, Western University, London, ON, Canada.
¹⁴ Juravinski Cancer Centre, McMaster University, Hamilton, ON, Canada.
¹⁵ Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.

PMID: 37914579
DOI: 10.1016/j.euo.2023.10.002

Abstract

Background: The role of cytoreductive nephrectomy (CN) has not yet been well characterized in the era of combination immunotherapy.

Objective: To evaluate characteristics and outcomes for patients with metastatic renal cell carcinoma (mRCC) who received immuno-oncology (IO)-based combination therapy according to CN status.

Design, setting, and participants: Using the International mRCC Database Consortium (IMDC), patients with mRCC who received frontline IO-based combinations were included. Upfront CN was defined as CN up to 3 mo before diagnosis of metastatic disease but before systemic therapy initiation. Deferred CN was defined as CN after systemic therapy initiation.

Outcomes measurements and statistical analysis: Overall survival (OS) from initiation of systemic therapy was estimated via Cox proportional-hazards regression. A 12-mo landmark time and a time-varying covariate for CN status were used to mitigate potential bias.

Results and limitations: Of the 385 patients eligible for landmark analysis, 24, 182, and 179 underwent deferred CN, upfront CN, and no CN, respectively. Patients in the no CN subgroup were older (63 yr vs 57 yr in the deferred CN subgroup and 60 yr in the upfront CN subgroup; p = 0.001) and a higher proportion had bone metastases (44% vs 26% in the deferred CN subgroup and 23% in the upfront CN subgroup; p < 0.001). A lower proportion of patients in the upfront CN subgroup had IMDC poor risk (23% vs 43% in the no CN subgroup and 47% in the deferred CN subgroup; p < 0.001). On multivariable analysis, CN receipt was an independent favorable prognostic factor (hazard ratio 0.45, 95% confidence interval 0.26-0.78; p = 0.005). The study is limited by the lack of randomization and its retrospective nature.

Conclusions: Despite changes in practice patterns with the advent of novel therapeutic agents, CN may still serve as an effective surgical intervention in carefully selected patients.

Patient summary: For patients with metastatic kidney cancer, surgery to remove the primary tumor was traditionally the treatment of choice, but immunotherapy drugs are now another option for these patients. We analyzed data for contemporary patients with metastatic kidney cancer who received combination immunotherapy as their first treatment. We found that in selected patients receiving immunotherapy, surgery to remove the primary tumor as well can result in better prognosis.

Keywords: Cytoreduction surgical procedures; Immune checkpoint inhibitors; Nephrectomy; Prognosis; Renal cell carcinoma.