Reduced Mortality and Radiation Necrosis After Surgery With Postoperative Stereotactic Radiation in Patients With Multiple Brain Metastases

BACKGROUND AND OBJECTIVES Although stereotactic radiation has frequently supplanted whole-brain radiation therapy (WBRT) in treating patients with multiple brain metastases, the role of surgery for these patients remains unresolved. No randomized trials have compared surgical resection with postoperative stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) to SRS/SRT alone. Previous studies addressing surgery for patients with multiple brain metastases are often limited by small sample sizes, a lack of appropriate comparison groups, or a focus on patients treated before recent advances in targeted therapy and immunotherapy. We compared outcomes in patients with multiple brain metastases treated with surgical resection and postoperative SRS/SRT to those treated with SRS/SRT alone. METHODS We studied 734 patients with multiple newly diagnosed brain metastases (surgery with SRS/SRT, n = 228; SRS/SRT alone, n = 506) from 2011 to 2022 in a retrospective, single-institution cohort. Patients who received upfront whole-brain radiotherapy were excluded. Cox proportional hazards models were constructed for overall survival and additional intracranial outcomes. RESULTS After adjustment for potential confounders, surgery with postoperative SRS/SRT was associated with decreased all-cause mortality compared with SRS/SRT alone (hazard ratio [HR]: 0.67, 95% CI [0.50-0.89], P = 5.56 × 10-3). The association between surgical resection and overall survival was replicated in a subset of the cohort after cardinality matching (HR: 0.64, 95% CI [0.46-0.88], P = 6.68 × 10-3). Patients with melanoma benefited significantly less from surgical resection compared with patients with other tumor types, most notably non-small-cell lung cancer. Compared with definitive SRS/SRT, cavity SRS/SRT was associated with a significantly reduced risk of both symptomatic radiation necrosis (HR: 0.22, 95% CI [0.08-0.59], P = 2.70 × 10-3) and radiographic radiation necrosis (HR: 0.23, 95% CI [0.09-0.57], P = 1.43 × 10-3) in multivariable models. CONCLUSION In patients with multiple brain metastases, surgical resection before SRS/SRT is associated with reduced mortality and radiation necrosis. Prospective studies may further delineate patient populations that benefit from aggressive local, brain-directed treatment even with significant intracranial disease burden.