Assessment of Bone Metastases, Skeletal-Related Events and Bone-Targeting Agents in Patients With Metastatic Renal Cell Carcinoma Receiving First-Line Systemic Therapy (Meet-URO 33 Study Subanalysis).

INTRODUCTION: Bone metastases (BMs) in patients with metastatic renal cell carcinoma (mRCC) negatively affect survival, quality of life, and increase the risk of skeletal-related events (SREs). Evidence remains limited in the era of first-line immune-based combinations. PATIENTS AND METHODS: Meet-URO 33 is an Italian multicenter observational retrospective-prospective study enrolling mRCC patients receiving first-line therapy. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), clinical characterization, incidence of SREs, and impact of bone-targeting agents (BTAs). Survival was analyzed using the Kaplan-Meier method, log-rank test and Cox proportional hazards model. RESULTS: A total of 1696 patients enrolled between 2021 and 2025 were included; 526 (31%) had BMs at metastatic diagnosis. Patients with BMs more frequently had poorer performance status and unfavorable International mRCC Database Consortium (IMDC) risk. The presence of BMs was associated with significantly worse OS (median 26.9 vs. 102.1 months; hazard ratio [HR] 0.53; P < .001) and worse PFS (median 14.2 vs. 19.4 months; HR 0.71; P < .001), with OS and PFS varying according to first-line regimen. Worse OS persisted across IMDC risk classes and treatment types; PFS differences were not significant in favorable/intermediate IMDC risk groups and with tyrosine kinase inhibitor monotherapy. Neither anatomical site nor number of BMs significantly affected OS. SRE incidence in patients with BMs was 26.8%, more frequent with spinal, rib, or other-site involvement, and more common in BTA-treated patients (22.2% vs. 13.7%, P = .03), likely reflecting selection bias. CONCLUSION: BMs are confirmed a negative prognostic factor in mRCC involving persistent unmet clinical needs.