Radiotherapy-based metastasis-directed therapy (MDT) has emerged as a treatment strategy for oligometastatic clear cell renal cell carcinoma (ccRCC). However, optimal integration of MDT with immune checkpoint inhibition (ICI) is unclear, especially in light of the M1 no evidence of disease subgroup analysis of KEYNOTE-564. We undertook an exploratory cohort study of two previously reported trials evaluating either MDT+ICI (NCT02855203) or MDT (NCT03575611) for oligometastatic ccRCC. The objective was primarily to compare RECIST-defined progression-free survival (PFS) and secondarily to compare peripheral immune populations. Among the 150 patients included in the analysis (MDT+ICI: 30; MDT: 120), the MDT+ICI cohort had more metastases (median 3 vs 1) and was slightly younger (median 62 vs 66) than MDT. After a median follow-up time of 34 mo, there was evidence for longer PFS after MDT+ICI vs MDT that did not reach statistical significance (hazard ratio, 0.57; 95% confidence interval: 0.32-1.02; p = 0.058). Interaction testing demonstrated greater PFS benefit with MDT+ICI among patients with previous receipt of systemic therapy. Immediate systemic induction of activated CD8+ T cells (ICOS+) was more common after MDT+ICI, as were decreases in less functional CD8+ T cell subsets. Taken together, this study provides evidence that adding maintenance ICI to MDT improves clinical outcomes for patients with oligometastatic ccRCC. MDT+ICI-evoked immunomodulatory signals are promising and support the observed superiority in clinical outcomes. The A Randomized Trial of Maintenance Systemic Therapy After Radiation for Oligometastatic Renal Cell Carcinoma (ASTROs) trial (NCT06004336) has been initiated to test the hypotheses generated by the present study.
European urology. 2026 Apr 27 [Epub ahead of print]
Alexander D Sherry, Van To, Criselle D'souza, Simin Kiany, Niko Thio, Suyu Liu, Xiaowen Sun, Becky Castle, Sean Macdonald, Haesun Choi, Aaron Seo, Kieko Hara, David Pryor, Arun Azad, Ben Tran, Lewis Au, Lavinia Spain, Ethan B Ludmir, Eric Jonasch, Nizar M Tannir, Pavlos Msaouel, Paul Neeson, Cara Haymaker, Chad Tang, Shankar Siva
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA., Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia., Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia., Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Australia., Department of Abdominal Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Queen's University Medical Group, Honolulu, HI, USA., Department of Urology and Radiation Oncology, Princess Alexandra Hospital, Woolloongabba, Brisbane, Queensland, Australia; Queensland University of Technology, Brisbane, Queensland, Australia., Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia., Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Genitourinary Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: ., Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia.