Immune Checkpoint Inhibitors Plus Debulking Surgery for Patients With Metastatic Renal Cell Carcinoma: Clinical Outcomes and Immunological Correlates of a Prospective Pilot Trial

Authors

Sangeeta Goswami
Jianjun Gao
Sreyashi Basu
Daniel D Shapiro
Jose A Karam
Rebecca Slack Tidwell
Kamran Ahrar
Matthew T Campbell
Yu Shen
Alexandro E Trevino
Aaron T Mayer
Alexsandra B Espejo
Christian Seua
Marc D Macaluso
Yulong Chen
Wenbin Liu
Zhong He
Shalini S Yadav
Ying Wang
Priya Rao
Li Zhao
Jianhua Zhang
Sonali Jindal
Nizar M Tannir
Andrew Futreal
Linghua Wang
Padmanee Sharma

Publication Date

2-21-2025

Journal

Nature Communications

Abstract

Surgical removal of primary tumors reverses tumor-mediated immune suppression in pre-clinical models with metastatic disease. However, how cytoreductive surgery in the metastatic setting modulates the immune responses in patients, especially in the context of immune checkpoint therapy (ICT), is not understood. We report the first prospective, pilot, non-comparative clinical trial (NCT02210117) to evaluate the feasibility, clinical benefits, and immunologic changes of combining three different ICT-containing strategies with cytoreductive surgery or biopsy for patients with metastatic clear cell renal cell carcinoma. Primary safety endpoint of this trial has been met, with 43 patients completing cytoreductive surgery, 36 patients undergoing post-ICT biopsy, and 25 patients without either procedure due to progressive disease or toxicities or withdrawal of consent (total N = 104). Patients receiving ICT with cytoreductive surgery or biopsy, did not experience additional ICT- or procedure-related toxicities. The median overall survival was 54.7 months for patients who received ICT plus cytoreductive surgery. Immune-monitoring studies demonstrated that cytoreductive surgery increased antigen-presenting dendritic cell population and decreased KDM6B-expressing immune-suppressive myeloid cells in the peripheral blood. This study highlighted the feasibility of combining ICT with cytoreductive surgery in a metastatic setting and demonstrated the potential enhancement of immune responses following ICT plus cytoreductive surgery.

Keywords

Humans, Carcinoma, Renal Cell, Cytoreduction Surgical Procedures, Pilot Projects, Kidney Neoplasms, Immune Checkpoint Inhibitors, Female, Male, Middle Aged, Prospective Studies, Aged, Treatment Outcome, Adult, Dendritic Cells, Combined Modality Therapy, Neoplasm Metastasis

DOI

10.1038/s41467-025-57009-z

PMID

39984485

PMCID

PMC11845590

PubMedCentral® Posted Date

2-21-2025

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes