Risk Factors and Genomic Characteristics of Recurrent Meningiomas Identified Through Routine Clinical Testing

Objective Although most meningiomas are benign, recurrence remains a key determinant of patient prognosis. Despite numerous studies addressing recurrence risk factors, comprehensive clinical analyses specifically focusing on recurrence-related determinants are still limited. This study aimed to identify factors influencing time to recurrence and, by integrating real-world molecular diagnostic data, to provide evidence for preoperative decision-making and individualized clinical and neuroimaging follow-up strategies. Methods We retrospectively reviewed 991 patients with meningiomas who underwent surgery at our center between January 2019 and May 2024. Sixty-five patients who underwent reoperation for recurrent intracranial meningiomas with complete clinical data were included. Clinical variables analyzed included age, sex, tumor location, tumor–venous sinus relationship, extent of resection, WHO grade, and Ki-67 index at the initial surgery, as well as recurrence interval and progression-free survival (PFS). At recurrence, regrowth pattern, peritumoral edema, extent of resection, WHO grade, and Ki-67 index were also evaluated. Additionally, molecular testing was performed in 30 cases according to the 2021 WHO classification of central nervous system tumors, covering TERT promoter mutations (C228T, C250T), CDKN2A/B, PTEN, PIK3CA, and SMARCB1 mutations, as well as chromosomal copy number alterations. Results Among the 65 recurrent meningioma patients, PFS ranged from 4 to 286 months. By the last follow-up in May 2024, six patients had died—five from further recurrence and one from myocardial infarction—all with WHO grade III meningiomas. Univariate log-rank analysis revealed significant PFS differences between WHO grades I and II (p = 0.0112) and between grades I and III (p < 0.001), but not between grades II and III (p = 0.2585). Multivariate regression identified male sex (HR > 1, p < 0.05) and Ki-67 index ≥ 10% (HR > 1, p < 0.05) as independent adverse prognostic factors for PFS, whereas other variables were not statistically significant. In molecularly profiled cases, frequent alterations were observed in NF2, TERT C228T, and CDKN2A/B, alongside chromosomal deletions at 1p, 14q, and 22q, and amplifications at 1q and 19q. Notably, several histologically low-grade meningiomas were reclassified as WHO grade III based on molecular findings. Conclusion Male sex and high proliferative activity (Ki-67 ≥ 10%) were independently associated with shorter PFS, suggesting the need for intensified surveillance and more aggressive therapeutic strategies in these patients. Furthermore, the integration of molecular classification in real-world settings enhances prognostic precision and underscores the clinical importance of incorporating gene sequencing and chromosomal copy number testing into routine practice.