Objective: Brain metastases (BMs) are the most common CNS tumors, yet their prevalence is difficult to determine. Most studies only report synchronous metastases, which make up a fraction of all BMs. The authors report the incidence and prognosis of patients with synchronous and metachronous BMs over a decade.
Methods: Study data were obtained from the TriNetX Research Network. Patients were included if they had a primary cancer diagnosis and a BM diagnosis, with primary cancer occurring between January 1, 2013, and January 1, 2023. Metachronous BM was defined as BM diagnosed more than 2 months after the primary cancer. Cohorts were balanced by propensity score matching for age, extracranial metastasis, and antineoplastic or radiation therapy. Kaplan-Meier plots were used to evaluate survival differences between synchronous and metachronous BMs and associations with clinical conditions. A log-rank test was used to evaluate BM-free survival for metachronous BM and overall survival (OS) for all BMs. Hazard ratios and 95% CIs were calculated.
Results: Of the 11,497,663 patients with 15 primary cancers identified, 300,863 (2.6%) developed BMs. BMs most commonly arose from lung and breast cancers and melanoma. Of all BMs, 113,827 (37.8%) presented synchronously and 187,036 (62.2%) presented metachronously. Lung and bronchial cancer had the highest metastasis rate (11.0%) and the highest synchronous presentation (51.0%). For metachronous presentations, the time from primary diagnosis to metastasis ranged from 1.3 to 2.5 years, averaging 1.8 years. Metachronous BM diagnosis was associated with longer survival over synchronous BM from primary diagnosis (11.54 vs 37.41 months, p < 0.0001), but shorter survival than extracranial metastases without BM (38.75 vs 69.18 months, p < 0.0001). Antineoplastic therapy prior to BM was associated with improved BM-free survival (4.46 vs 17.80 months, p < 0.0001) and OS (25.15 vs 42.26 months, p < 0.0001). Radiotherapy showed a similar effect that was statistically significant but modest for BM-free survival (5.25 vs 11.44 months, p < 0.0001) and OS (30.13 vs 32.82 months, p < 0.0001).
Conclusions: The majority of BMs present metachronously and arise within 2 years of primary cancer diagnosis. The substantial rate of BMs presenting within 6 months of primary cancer, especially liver, lung, and pancreatic cancer, may guide future recommendations on intracranial staging. Antineoplastic therapy prior to the development of BM may prolong the time before metastasis and improve survival. Further characterization of this population can better inform screening, prevention, and treatment efforts.
Keywords: brain metastasis; epidemiology; metachronous metastasis; populational studies.