Aggressive Pituitary Adenomas: Clinical Predictors for Rapidly Recurrent Pituitary Adenomas—Looking Beyond Proliferative Markers

Objective: Pituitary adenomas (PAs) are benign slow-growing tumors that can be managed by surgical resection, radiation therapy, or medical treatment. However, a subset of PAs exhibits a more aggressive behavior, and a clear definition is yet to be determined. Previously, aggressive subtypes, termed atypical PAs, were defined by a high mitotic index and p53 expression. However, this definition was abandoned as more recent studies have shown that a significant number of PAs with aggressive behavior had low mitotic indices and lacked p53 expression. This study aimed to identify clinical predictors for aggressive behavior.

Methods: A database of patients treated for PAs between 2013 and 2023 at the authors’ institution was screened for PAs with aggressive behavior. In this study, we defined aggressive behavior as actual tumor regrowth, evidenced by MRI within 18 months after initial surgical or radiosurgical treatment. Potential predictors analyzed included gender, age, initial adenoma size, Knosp-Steiner (KS) grades, adenoma types, and intervention-free survival (IFS) for recurrences. To minimize confounding bias, these variables were included in a generalized linear model.

Results: Out of 700 patients treated for PAs, 153 (22%) required interventions for recurrence or progression. Among the patients, 25 (3.5%) met our criteria for aggressive behavior. Aggressive PAs had an average IFS of 11.3 (±4.9) months compared with 48.3 (±61.4) months for non-aggressive PAs (p < 0.0001). Compared with the overall non-aggressive cohort (n = 675), aggressive PAs were larger at initial diagnosis (25.6 mm ± 11.2 vs. 19.58 mm ± 12.22, p = 0.01), and had higher rates of KS grades 3 to 4 (60 vs. 32%, p = 0.004). Additionally, we found a higher incidence of males with prolactinomas (12 vs. 2.5%, p = 0.031) and silent corticotropic PAs (20 vs. 2.5%, p = 0.01).

Conclusion: The following clinical predictors correlated significantly with aggressive behavior of PAs: larger tumor size, higher KS grades, silent corticotropic PAs, and male patients with prolactinomas. This subgroup of patients should be monitored with higher intensity following initial treatment. Although further studies are necessary, our findings can help guide future treatment decisions to better identify and treat rapid recurrence following intervention for PAs.

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Artikel online veröffentlicht:
07. Februar 2025