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Updated: May 3, 2026
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Bone Metastases and Use of Bone Protective Agents for Metastatic Clear Cell Renal Cell Carcinoma: A Contemporary
Braden Millan1, Sunita Ghosh2, Naveen S Basappa2
1Urologic Oncology Branch, National Cancer Institute, Bethesda, MD.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Insights
Bone metastases (BM) are a poor prognostic factor in metastatic clear-cell renal cell carcinoma (mccRCC). Bone-protective agents (BPAs) did not improve outcomes in this patient group, indicating a need for further research.
Area of Science:
- Oncology
- Medical Science
- Clinical Research
Background:
- Bone metastases (BM) significantly worsen prognosis in metastatic clear-cell renal cell carcinoma (mccRCC).
- The role and utilization of bone-protective agents (BPAs) are understudied in the era of immune checkpoint inhibitors (IO).
Purpose of the Study:
- To evaluate oncologic outcomes in mccRCC patients with BM at diagnosis.
- To assess the utilization and impact of BPAs in a real-world cohort.
Main Methods:
- Retrospective analysis of 2482 mccRCC patients treated between 2011 and 2023.
- Kaplan-Meier estimates for time to treatment failure (TTF) and overall survival (OS).
- Cox proportional hazards models for cohort comparisons.
Main Results:
- 38.5% of patients had BM at diagnosis; 22.0% received BPAs.
- BM presence was associated with significantly shorter median OS (35.0 vs. 54.2 months).
- BPAs were not linked to improved TTF or OS in BM+ patients.
Conclusions:
- BM remain a significant negative prognostic factor in mccRCC.
- BPAs did not demonstrate a survival benefit in this cohort.
- Further investigation is needed to understand BPA efficacy, particularly regarding skeletal-related events.
