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Randomized Controlled Trial
. 2024 Feb 24;24(1):260.
doi: 10.1186/s12885-024-11987-3.

Multicenter randomized trial of deferred cytoreductive nephrectomy in synchronous metastatic renal cell carcinoma receiving checkpoint inhibitors: the NORDIC-SUN-Trial

Laura Iisager  1 , Johanne Ahrenfeldt  1 , Frede Donskov  2   3 , Börje Ljungberg  4 , Axel Bex  5 , Lars Lund  6 , Iben Lyskjær #  1 , Niels Fristrup #  7
Affiliations
Randomized Controlled Trial

Multicenter randomized trial of deferred cytoreductive nephrectomy in synchronous metastatic renal cell carcinoma receiving checkpoint inhibitors: the NORDIC-SUN-Trial

Laura Iisager et al. BMC Cancer. .

Abstract

Background: Primary tumor removal by cytoreductive nephrectomy in synchronous metastatic renal cell carcinoma patients has been investigated in the context of various treatment regimens. Two randomized controlled trials investigated the role and timing of cytoreductive nephrectomy in the era of targeted therapy and demonstrated that upfront nephrectomy should no longer be performed when patients require systemic therapy. Superiority of checkpoint immunotherapy agents has led to a paradigm change from targeted therapies to immunotherapy-based first-line treatment in patients with primary metastatic disease; thus, deferred cytoreductive nephrectomy needs to be verified in the immunotherapy setting. Furthermore, a need exists for personalizing treatment choices for the individual patient to avoid unnecessary overtreatment.

Methods/design: To explore the impact of cytoreductive nephrectomy in this patient group receiving checkpoint immunotherapy, we initiated a randomized, controlled trial comparing deferred cytoreductive nephrectomy with no surgery. The trial integrates a comprehensive translational research program with specimen sampling for biomarker analysis.

Discussion: The trial aims to show that deferred cytoreductive nephrectomy improves overall survival in patients with synchronous metastatic renal cell carcinoma, and furthermore, to identify relevant biomarkers for personalized renal cancer management.

Trial registration: ClinicalTrials.gov NCT03977571 June 6, 2019.

Keywords: Biomarkers; Deferred cytoreductive nephrectomy; Immunotherapy; Synchronous metastatic renal cell carcinoma; Translational research.

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Conflict of interest statement

NF has performed consultancy for Pfizer, Eisai, MSD, BMS, and has received speaker honoraria from AstraZeneca, BMS, MSD. BL: Company speaker: Novartis, IPSEN, BMS; Company consultant: Janssen, Ipsen, MSD; Trial participation: Jenssen—Astellas – Medivation. AB: grants from Pfizer and steering committee membership of Roche and BMS, consultancy for IPSEN. The other authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
Study design. Arm A: Deferred CN followed by nivolumab or TKI-IO therapy. Arm B: No surgery, nivolumab or TKI-IO therapy. Arm C: Patients not eligible for randomization into Arm A or B. CN: Cytoreductive Nephrectomy; IO: Immunotherapy; mRCC: metastatic Renal Cell Carcinoma; Nivo: Nivolumab; TKI: Tyrosine Kinase Inhibitor. Generated with BioRender.com
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