Abstract
Leptomeningeal disease (LMD) is a serious complication of systemic cancer, most commonly associated with brain metastases. However, vertebral bone metastases may also serve as a route for cerebrospinal fluid involvement, though this pathway is less well characterized. Using the TriNetX global health research network (N = 133 million), we identified 7,887 adult patients with vertebral metastases from common solid tumors (lung, breast, prostate, colorectal, renal, melanoma, thyroid), excluding those with brain metastases or other potential sources of LMD. Among these, 145 patients (1.9%) developed LMD following vertebral metastasis alone. Breast cancer had the highest rate of LMD (3.0%), followed by colorectal (1.8%), thyroid (1.8%), and melanoma (1.7%). The median time from vertebral metastasis to LMD diagnosis was 95 days, which was significantly longer than the 60-day median in patients whose LMD originated from brain metastases (p < 0.001). Patients who developed LMD had shorter overall survival compared to those with vertebral metastases who did not (median 164 vs. 370 days, p = 0.0006; HR 0.61, 95% CI 0.46–0.81). In the breast cancer subgroup, the presence of LMD was associated with a substantial reduction in survival (median 170 vs. 1,001 days, p = 0.0032). Patients with LMD were also more likely to require hospice or palliative care (39.6% vs. 22.2%, p < 0.001), while those without LMD more often reported pain (67.1% vs. 52.4%, p = 0.0113) and emotional distress (45.8% vs. 26.4%, p = 0.007). Survival after LMD diagnosis was similar between patients with brain and vertebral metastases (p = 0.966), reflecting a poor prognosis regardless of origin. These findings highlight vertebral metastases as a potential source of LMD and suggest a need for heightened clinical awareness, earlier diagnostic consideration, and further investigation into targeted surveillance strategies for at-risk patients.