Timing of bone-modifying agent initiation and skeletal-related event risk in patients with bone metastases from solid tumors: a retrospective landmark and propensity score-matched analysis.

PURPOSE: The optimal timing for initiating bone-modifying agents (BMAs) after the diagnosis of bone metastasis remains unclear. We evaluated the association between the timing of BMA initiation and the subsequent risk of skeletal-related events (SREs). METHODS: Patients with solid tumors who received BMA therapy for bone metastasis at a single institution between 2010 and 2024 were retrospectively analyzed. To minimize immortal time bias, a landmark analysis was performed at 6 months after the diagnosis of bone metastasis. Patients who remained under follow-up and had not experienced an SRE by the landmark were classified into the Early group if BMA therapy was initiated by the landmark; otherwise, they were assigned to the Delayed group. One-to-one propensity score matching (PSM) was performed to balance baseline characteristics between the groups. The primary endpoint was the time from the landmark to the first SRE. RESULTS: Following PSM, 134 patients were included in each group. SREs were observed in 86 patients during follow-up after the landmark. The Delayed group had a significantly higher subsequent risk of SREs than the Early group (hazard ratio (HR), 1.82; 95% confidence interval (CI), 1.16-2.84; P < 0.01). CONCLUSIONS: Among patients who remained under follow-up and SRE-free at the 6-month landmark, delayed BMA initiation was associated with a higher subsequent risk of SREs than early initiation. Thus, prolonged delay in BMA initiation after the diagnosis of bone metastasis may be clinically relevant to subsequent SRE risk.