Characterizing intradural spinal metastasis in the metastatic cascade: clinical course, dissemination timing, and molecular features in 69 patients.

INTRODUCTION: Metastatic cancers to the central nervous system (CNS) usually affect the brain, but a small and clinically significant portion also affect the intradural spinal space. Here, we characterize the molecular features of metastatic intradural spinal disease and describe the metastatic chronology and timeline such cancers go through to reach this space. METHODS: All patients with MRI spine findings of intramedullary or leptomeningeal lesions from 2020-2025 at a tertiary academic center were screened. Patients with primary CNS cancer or non-cancer diagnoses were excluded. Demographic information, imaging findings, dates of primary cancer and metastasis detection, and molecular data across disease sites were collected. The primary outcome of interest was overall survival (OS) after primary diagnosis. RESULTS: 69 patients met inclusion criteria out of 1401 patients screened. The most common primary pathologies were lung (33.3%) and breast (31.9%). 11.6% of patients underwent surgery for intradural disease. The distribution of intradural spine disease on initial detection was 55.1% cervical, 65.2% thoracic, and 76.8% lumbar. The mortality rate was 87.0% within a median follow-up of 42.0 (IQR 20.6-72.9) months after primary cancer diagnosis. The median time to any metastasis was 0.5 (0-6.7), to the brain was 14.9 (0.6-42.7), to the osseous spine was 19.4 (0.7-38.9), and to the intradural spine was 29.5 (14.0-52.6) months. Targetable mutations were noted in 46.4% of primary lesions and such patients trended towards improved OS (51.7 months, 31.2-105.2) compared to patients without (30.1 months, 12.6-58.9, p = 0.072). This difference was driven by patients with such biomarkers qualifying for targeted therapies, which demonstrated improved OS (56.2 vs 31.2 months, p = 0.029). CONCLUSION: Targetable biomarkers are present in nearly 50% of primary lesions for patients who develop spinal intradural disease, and regular molecular characterization and sequencing of this space (e.g. CSF liquid biopsy) could have a clinically meaningful impact on these patients.