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.

purposeThe 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).

methodsPatients 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.

resultsFollowing 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).

conclusionsAmong 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.