The Identification of Risk Factors for Symptomatic Spinal Metastasis Onset: A Prospective Cohort Study of 128 Asymptomatic Spinal Metastasis Patients

SIMPLE SUMMARY: The risk factors for symptomatic spinal metastasis (SSM) onset remain unclear. This prospective cohort study aimed to statistically analyze the significant risk factors. One hundred and twenty-eight asymptomatic patients were prospectively registered. Data were collected from sixteen candidates regarding independent demographic and clinical factors, including Spinal Neoplastic Instability Score (SINS). Multivariate analysis was performed to identify the risk factors for SSM onset. Furthermore, the threshold was calculated from the receiver operating characteristic curve using the Youden index. Thirty-seven patients (28.9%) developed SSM during the follow-up period. The total SINS was identified as the most significant factor. The cut-off value for the SINS was 9.5 (sensitivity: 67.6%; specificity: 83.5%). This study identified the significant risk factors for SSM onset and the threshold of the SINS. If long-term survival is expected, patients with a SINS ≥ 10 should be considered for intervention to prevent SSM. ABSTRACT: Background: Symptomatic spinal metastasis (SSM) decreases the activities of daily living (ADL) and quality of life of cancer patients. However, the risk factors for SSM onset remain unclear. This prospective cohort study aimed to statistically analyze the significant risk factors. Methods: From 2016 to 2018, 210 consecutive patients with spinal metastases were prospectively registered. Patients with SSM at the first consultation and those who were unable to be followed-up owing to poor general condition were excluded. The demographic factors (age, sex, primary cancer, performance status, and ADL), clinical factors (radiation therapy, chemotherapy, molecularly targeted drugs, and bone-modifying agents (BMAs)), and Spinal Neoplastic Instability Score (SINS) were evaluated. Multivariate analysis was performed to identify the risk factors for SSM onset. Furthermore, the threshold was calculated from the receiver operating characteristic curve using the Youden index. Results: Thirty-nine patients who presented with SSM at the first consultation and 43 patients who were unable to be followed-up owing to poor general condition were excluded. Finally, 128 asymptomatic patients were included. Thirty-seven patients (28.9%) developed SSM during the follow-up period. The total SINS (OR: 1.739; 95% CI: 1.345–2.250) was identified as the most significant factor. The cut-off value of the SINS was 9.5 (sensitivity: 67.6%; specificity: 83.5%). Twenty-five (62.5%) of the forty patients with a SINS ≥ 10 developed SSM within a mean of 5.5 months (95% CI: 1.17–9.83). Furthermore, all patients with a SINS ≥ 13 developed SSM (n = 5) within a mean of 1.37 months (95% CI: 0.0–3.01). Conclusions: This study identified the significant risk factors for SSM onset and the threshold of the SINS. If long-term survival is expected, patients with a SINS ≥ 10 should be considered for intervention to prevent SSM.