Meningeal metastases in castrate resistant prostate cancer: institutional series and systematic review
Adree Khondker1, Jethro Kwong2, Dan Budiansky1, Christropher Tran1, Emily Evans1, Lucshman Raveendran2, Ishan Aditya1, Amna Ali3, Yingming A. Chen4, Andrew Feifer2,3,5.
1Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; 2Division of Urology, Department of Surgery, University of Toronto, Toronto, ON, Canada; 3Institute for Better Health, Trillium Health Partners, Mississauga, ON, Canada; 4Department of Diagnostic Imaging, Trillium Health Partners, Mississauga, ON, Canada; 5Carlo Fidani Regional Cancer Center, Trillium Health Partners, Mississauga, ON, Canada
Contemporary studies suggest that the incidence of meningeal metastases (MM) is rising in castrate-resistant prostate cancer (CRPC). The natural history and survival of patients with MM is not well characterized, especially in the era of novel hormonal therapies. We set out to describe MM in a contemporary series of CRPC patients.
We reviewed a CRPC cohort at Trillium Health Partners from 2012-2020. Patient and disease features, imaging characteristics, and survival outcomes were included in this analysis. MM was defined by intracranial or intraspinal tumor localization without contiguous osseous involvement. We also conducted a systematic review and included all studies on patients with prostate cancer progressing to MM (PROSPERO: CRD42021232801).
Six out of the 275 patients (2.2%) with CRPC at our institution developed MM. At the time of CRPC, the patients who developed MM were significantly younger, had lower baseline hemoglobin, higher LDH, and elevated ALP compared to those who did not develop MM. The systematic review yielded an additional 11 observational studies (135 patients) which were pooled with our series. The most common presenting symptoms were cranial nerve deficits, headache, or gross motor deficits. Mean age at progression to MM was 63.0 years (range: 58.4, 70.9). Mean time from first diagnosis of prostate cancer to MM was 54.6 months (range: 21.0, 101.5). The mean time from MM to death was 9.0 months (range: 2.6, 23.0). Patients requiring resection for MM (i.e., from subdural hemorrhage) had shorter survival compared to patients receiving only radiation or supportive therapy (p=0.01).
We describe the largest pooled analysis of patients with MM in CRCP. Neurological symptoms of any kind in the setting of CRPC and especially in younger patients warrants urgent radiographic investigation. Further studies to assess for clinical and biological predictive factors is warranted.