Bone Metastases (BM) are associated with a poor prognosis in metastatic clear-cell renal cell carcinoma (mccRCC). In the immune checkpoint inhibitor (IO) era, evidence for and use of bone-protective agents (BPAs) is limited. We investigated oncologic outcomes in mccRCC patients with BM at diagnosis and the use of BPA in a contemporary real-world cohort.
We identified patients with mccRCC treated between 2011 and 2023. Adjusted Kaplan-Meier estimates were used to estimate time to treatment failure (TTF) and overall survival (OS), and cohort comparisons were performed using Cox proportional hazards model.
Of 2482 patients with mccRCC, 956 (38.5%) had BM at diagnosis, and 210 (22.0%) received a BPA. First-line tyrosine kinase inhibitor (TKI) containing regimen use was higher in BM + patients (79.3% vs. 74.9%). First-line median TTF was similar (9.4 vs. 8.7 mos); however, median OS was longer in BM- vs. BM + patients: 54.2 vs. 35.0 mos (HR, 1.32; P < .0001), irrespective of first-line therapy. BPA omission in BM + only patients resulted in a non-statistically significant shorter TTF (8.3 vs. 10.4 mos; HR, 0.91) and OS (34.3 vs. 38.5 mos; HR, 1.00). Receipt of first-line IO/IO (HR, 0.69; 0.60-0.81) and IO + TKI (HR, 0.61; 0.54-0.74) compared to monotherapy TKI resulted in a significantly longer OS in all patients, though not in BM + only patients.
BM remain a poor prognostic factor in mccRCC in this contemporary cohort. Despite more use in BM + patients, BPAs were not associated with improved TTF or OS, though their potential impact on skeletal-related events is not captured in the current study.
Clinical genitourinary cancer. 2026 Mar 27 [Epub ahead of print]
Braden Millan, Sunita Ghosh, Naveen S Basappa, Lori Wood, Bimal Bhindi, Frederic Pouliot, Rodney H Breau, Antonio Finelli, Rahul K Bansal, Jeffrey Graham, Georg A Bjarnason, Dominick Bosse, Vincent Castonguay, Eric Winquist, Daniel Yick Chin Heng, Christian K Kollmannsberger, Aly-Khan A Lalani
Urologic Oncology Branch, National Cancer Institute, Bethesda, MD., Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB., Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, NS., Southern Alberta Institute of Urology, Calgary, AB., CHU de Quebec, Université Laval, Quebec City, QC., Ottawa Hospital, Ottawa, ON., University of Toronto, Toronto, ON., St Joseph Healthcare Hamilton, Hamilton, ON., CancerCare Manitoba, University of Manitoba, Winnipeg, MB., Sunnybrook Odette Cancer Centre, Toronto, ON., University of Ottawa, Ottawa, ON., Hotel Dieu de Quebec, Quebec, QC., Verspeeten Family Cancer Centre at London Health Sciences Centre and Western University, London, ON., Arthur J.E. Child Comprehensive Cancer Centre, University of Calgary, Calgary, AB., British Columbia Cancer Agency, Vancouver Centre, Vancouver, BC., Juravinski Cancer Centre, McMaster University, Hamilton, ON. Electronic address: .