1065 Impact of Somatic Mutations on Survival and Neurological Outcomes in Spinal Metastases From Prostate Cancer

INTRODUCTION: Prostate cancer with spinal metastases (PCSM) is associated with high morbidity and mortality. The impact of somatic mutations on the prognosis of spinal metastases, however, remains unclear. METHODS: We conducted a retrospective analysis of 68 PCSM patients at Johns Hopkins from 2013 to 2023, examining the influence of specific mutations and targeted therapies on prognosis. Criteria included a PCSM diagnosis and available genetic profiling. Primary outcomes were overall survival (OS) rates, identification of genetic biomarkers, neurological outcomes via Frankel scores, and impacts of various anticancer therapies. RESULTS: Median age was 69 years. All patients (n=68) had adenocarcinoma. The mortality rate was 66% with a median OS of 6 years. Seventy-two genetic biomarkers were identified. An accelerated failure time model (AFT) showed that radiotherapy to the prostate was associated with increased OS (TR=1.805, p=0.001), while smoking status (TR=0.625, p<0.001) and PTEN gene mutations (TR=0.504, p=0.006) were associated with reduced OS. Kaplan Meier analysis associated PTEN mutations with reduced median OS (3.50 vs 9.49 years; p=0.001) and shorter time-to-death following spinal metastases (2.04 vs 3.15 years; p=0.01). No differences were observed in median OS or time-to-death after spinal metastases among patients with or without androgen receptor splice variant-7, prostate-specific membrane antigen, TP53, or other analyzed biomarkers (p>0.05). Neither age, receipt of chemotherapy nor radiotherapy to spine correlated with OS (p>0.05). Only receipt of chemotherapy was associated with decreased postoperative Frankel Score (p=0.002). CONCLUSIONS: PTEN mutations and smoking status were associated with decreased OS in PCSM patients. PTEN mutations were also associated with shortened time to death after spinal metastases. Receipt of radiotherapy to the prostate was correlated with enhanced survival whereas receipt of radiotherapy to the spine was not.