Increased risk of early recurrence after gross-total resection in males with a WHO grade II meningioma: the impact of sex on recurrence and death in 5441 meningioma patients

Objective: Sex is a recognized factor in meningioma development, but its effect on recurrence and survival remains insufficiently studied in large clinical cohorts. This study aimed to investigate sex-specific differences in recurrence and survival across WHO grade I-III meningiomas, focusing primarily on outcomes after gross-total resection (GTR). Secondary analyses investigated outcomes after subtotal resection. Methods: Patients with intracranial meningiomas (n = 5441) from the international Personalized Neurosurgery database were identified; all were diagnosed according to the 2007 or 2016 WHO classification criteria, surgically treated, and followed between 1989 and 2019. The primary cohort consisted of 4372 patients who underwent Simpson grade I-III resections. Cumulative recurrence and survival risk were estimated. Multivariable logistic regression was used to obtain adjusted odds ratios comparing males to females. Counterfactual risk modeling and post hoc analyses were performed to assess age effects and center-level robustness. Results: Among patients with WHO grade II meningiomas, males had a significantly higher recurrence risk than females after GTR. At 5 years, males had more than two times the risk of recurrence (OR 2.21, 95% CI 1.42-3.42), declining toward no sex difference at 10 years. Counterfactual modeling showed an 83% higher 5-year recurrence risk in males with WHO grade II meningiomas (ratio of population-averaged risks 1.83, 95% CI 1.28-2.37), whereas no sex difference was observed if the same patients were instead classified as having WHO grade I meningioma. Post hoc analyses indicated that sex differences peaked in individuals of premenopausal age and diminished thereafter. The higher recurrence risk for males with WHO grade II meningiomas remained robust in sensitivity analyses. No consistent sex-related differences were detected in recurrence risk in WHO grade I meningioma or in the risk of death for WHO grade I or II meningioma. Among 1069 patients with Simpson grade IV resections, sex differences in recurrence and survival were not statistically significant. Conclusions: In this observational cohort, males with WHO grade II meningiomas who received GTR had a higher risk of early recurrence than females, an effect that appeared to be age dependent. These results do not exclude the possibility of sex-related risk differences in more slowly growing WHO grade I meningiomas with follow-up beyond 10 years. The findings raise the possibility of biological contributions linked to sex hormones, and the impact of sex on these survival outcomes should be validated in molecularly annotated cohorts.