This clinical trial, registered under NCT03750227, aims to compare the efficacy of pre-operative stereotactic radiosurgery (SRS) versus post-operative SRS in patients undergoing resection for brain metastases. The study’s primary goal is to determine if pre-operative SRS can extend the time to a composite endpoint of adverse outcomes, including local recurrence, leptomeningeal disease, or symptomatic radiation brain necrosis, compared to post-operative SRS. This randomized phase III trial will evenly distribute patients between two groups: one receiving SRS before surgery and the other receiving it afterward.

The significance of this study lies in its potential to establish a superior treatment paradigm for surgical brain metastases. If pre-operative SRS shows better outcomes, it could become the preferred method due to its convenience and the possibility of a shorter treatment timeline. Conversely, if post-operative SRS is superior, it will confirm its status as the standard of care. The trial will also assess overall survival, patient-reported outcomes, morbidity, and various other factors related to the treatment’s effectiveness and side effects. This research addresses a critical gap in knowledge regarding the optimal timing of SRS in the treatment of brain metastases.