Central nervous system metastases in gynecologic cancers: Real-world outcomes and prognostic factors.

e14012 Background: CNS metastases from gynaecologic cancer (GC) are uncommon and evidence guiding management is limited. We characterized a real-world cohort and evaluated outcomes and prognostic factors. Methods: We conducted a retrospective cohort study including patients with primary GC who developed radiologically confirmed parenchymal brain metastases and/or leptomeningeal disease between January 2013 and June 2025 at a comprehensive cancer center. Overall survival (OS) was assessed from primary diagnosis and from CNS involvement. Survival analyses used Kaplan–Meier methods and Cox regression. Prespecified multivariable models included intracranial disease burden (high: ≥3 lesions or leptomeningeal disease vs low: ≤2 lesions) and presence of extracranial metastatic disease at CNS diagnosis. Results: Among 13.505 GC patients, 33 (0.24%) developed CNS metastases. Median age at primary diagnosis was 59.2 years (34.5-76.4) and primary sites were endometrial (45.4%, 15/33), ovarian (21.2%, 7/33), cervical (18.2%, 6/33), and other/mixed (15.2%, 5/33). Median interval from diagnosis to CNS metastasis was 34.3 months (3.1–227.0). Most patients (93.9%, 31/33) were symptomatic and 90.9% (30/33) had extracranial metastases at CNS diagnosis. CNS involvement was parenchymal in 90.9% (30/33) and leptomeningeal in 9.1% (3/33). Among parenchymal cases, 56.7% (17/30) had multiple lesions and with ≥3 lesions 40.0% (12/30). Brain-directed management was supportive care (48.5%, 16/33), radiotherapy alone (24.2%, 8/33), multimodal therapy - surgery plus adjuvant radiotherapy/SRS (21.2%, 7/33), or surgery alone (6.1%, 2/33). Median OS from primary diagnosis was 40.9 months (95% CI: 16.4–65.45 months) and after CNS metastasis 2.17 months (6- and 12-month OS, 27.3% and 18.2%, respectively). Survival differed by strategy, with longer OS in patients receiving multimodal therapy compared with radiotherapy alone or supportive care (median 19.75 vs 2.96 vs 1.05 months). On multivariable analysis, higher CNS disease burden was associated with shorter OS (adjusted HR 2.72, 95% CI 1.24–5.97; P=0.012). Conclusions: CNS metastases from gynaecologic cancers were rare but associated with extremely poor prognosis, typically occurring in the setting of widespread extracranial disease. Intracranial disease burden and brain-directed treatment strategy were key prognostic factors. Selected patients with low CNS disease burden may achieve meaningful survival benefit from multimodal therapy.