Long-Term Outcomes and Predictors of Recurrence in a Very Large Cohort of Rathke's Cleft Cysts Receiving Transsphenoidal Surgery

Introduction: Rathke’s cleft cysts (RCCs) are benign epithelial lesions of the sellar and suprasellar region, often identified incidentally but capable of causing significant morbidity when symptomatic. Although most RCCs remain radiographically stable, a clinically meaningful subset exerts mass effect on the optic apparatus or pituitary gland, resulting in visual disturbances, hypopituitarism, and reduced quality of life. Surgical resection via endoscopic endonasal transsphenoidal surgery (TSS) is the treatment of choice for symptomatic RCCs, yet postoperative recurrence remains a vexing issue, with rates as high as 33% in some series. Despite prior studies, no robust clinical, radiographic, or surgical predictors of recurrence have been definitively validated. Objectives: To identify independent clinical, radiological, and intraoperative predictors of radiographic recurrence following transsphenoidal surgery for symptomatic Rathke’s cleft cysts, and to characterize associated endocrine and surgical outcomes. Methods: We conducted a retrospective cohort study of 130 adult patients who underwent endoscopic TSS for RCC at a tertiary academic pituitary center between 2008 and 2024. Clinical presentation, endocrine function, imaging characteristics, and operative variables were systematically reviewed. Multivariable and penalized logistic regression models were employed to determine predictors of recurrence, defined radiographically within a two-year postoperative window. Hormonal assays were performed longitudinally, and lesion morphology was assessed by experienced neuroradiologists. Binary logistic regression and three penalized regression models (Ridge, Lasso, Elastic Net) were constructed to identify independent predictors of new postoperative hormonal deficits. Model selection was based on Akaike Information Criterion (AIC). t -tests and chi square tests were not performed to avoid the high type 1 error rate seen with multiple testing. Results: Radiographic recurrence occurred in 25.8% of patients. Compared with non-recurrent cases, these patients were more frequently presented with preoperative hypopituitarism (25% versus 14.3%), visual disturbances (44.4% versus 33.7%), and systemic comorbidities such as diabetes mellitus (22.2% versus 6.1%). Radiographically, recurrent lesions demonstrated higher rates of rim enhancement (23.3% versus 11.2%) and preoperative stalk adherence (60.7% versus 44.2%), despite smaller average volumes. Intraoperatively, recurrence was significantly associated with CSF leak requiring sellar reconstruction (56.7% versus 35.7%) and a lower rate of gross total resection (29% versus 54.1%). Multivariate logistic regression identified gross total resection as a strong protective factor (OR 0.22, 95% CI 0.07–0.69), while suprasellar extension (OR 3.57, 95% CI 1.12–11.26) and rim enhancement (OR 3.01, 95% CI 1.02–9.43) independently predicted recurrence. Penalized logistic models confirmed the significance of these variables. Postoperatively, recurrent cases exhibited persistently higher rates of hyperprolactinemia and hypothyroidism, suggesting long-term hypothalamic-pituitary-axis disruption. Conclusion: In one of the largest single-institution series to date, we demonstrated that RCC recurrence was significantly associated with identifiable preoperative and intraoperative features—namely, suprasellar location, rim enhancement, incomplete resection, and intraoperative CSF leak. These findings underscore the critical importance of achieving gross total resection when safe, recognizing high-risk imaging features, and minimizing intraoperative morbidity. This work provides a clinically actionable framework for preoperative risk stratification and may inform surgical planning and postoperative surveillance strategies. Publication History Article published online: 27 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany