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recurrence; tumoral progression; histopathology classification; risk factors; PANOMEN-3 application/pdf 10.1210/clinem/dgaf252 en Oxford University Press Validation and Limitations of the PANOMEN-3 Predictive Model for Tumor Recurrence and Progression in Pituitary Tumors Marta Araujo-Castro Edelmiro Menéndez Torre Claudia Lozano-Aida Rogelio García-Centeno Laura González Fernández Cindy Idrobo Estefanía Achote-Rea Ana Irigaray Echarri María Dolores Moure Rodríguez-Argulló Miguel Paja Fernando Guerrero-Pérez Justo P. Castaño María Dolores Ollero García Cristina Novo-Rodríguez Carmen Tenorio-Jimenéz Rocío Villar-Taibo Ignacio Bernabeu Everardo Díaz-López María Calatayud Cristina Alvarez-Escola Patricia Martín Rojas-Marcos José María Recio-Córdova Anna Aulinas Queralt Asla Roca María Dolores Aviles Elena López Mezquita María Fernández-Argüeso Inmaculada González Molero Ignacio Ruz-Caracuel Iban Aldecoa Julia García-Arabehety Elena Martínez-Sáez Felicia Hanzu Mónica Marazuela Manel Puig-Domingo Betina Biagetti DOI: 10.1210/clinem/dgaf252; The Journal of Clinical Endocrinology & Metabolism, 110, 12, 2025-04-25.; Abstract: Context: It has been proposed that the PANOMEN-3 classification may be useful to guide the prognosis and therapy of patients with pituitary tumors (PTs). However, the model has not yet been validated to date in order to assess its usefulness in routine clinical practice. Objective: The aim of our study was to validate the classification proposed by the PANOMEN-3 group for the prediction of tumor recurrence/progression in PTs. Methods: Multicenter national case–control study of patients with PTs followed for at least 5 years. Kaplan–Meier curves were used to assess the time to tumor recurrence/progression. Univariate and multivariate Cox regression analyses were used to estimate the hazard ratio (HR) and prognostic capacity of the classification proposed by the PANOMEN-3 group. Results: A total of 1143 patients were included. Pituitary surgery was performed in 814 patients and the remaining 329 patients were followed with active surveillance or medical treatment. After a median follow-up of 8.8 years (5-29.8), 253 patients experienced tumor recurrence or biochemical/radiological progression and were classified as cases. The other 890 patients were classified as controls. The mean follow-up from PT diagnosis to recurrence was 7.2 ± 5.4 years. The diagnostic accuracy of the PANOMEN-3 model to predict recurrence/progression was 75.6% (95% CI 0.716-0.796). Residual tumor (HR 2.20, P < .001), a hereditary syndrome (HR 5.15, P = .026), and active secretory status (HR 1.80, P = .021) were the most important variables in this model. Recurrence/progression rate increased with increasing PANOMEN-3 grade (2.5% in grade 0; 10.3% in grade 1, 33.7% in grade 2, and 33.3% in grade 3; P < .001). Conclusion: The predictive model proposed by the PANOMEN-3 group may be useful to guide the prognosis and therapy of PTs in the Spanish population since it offers a good accuracy to predict tumoral/biochemical recurrence and/or progression in operated and nonoperated patients. pituitary tumors recurrence tumoral progression histopathology classification risk factors PANOMEN-3 © The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society. PDFlib+PDI 9.0.7p3 (C++/Win64); modified using iTextSharp.LGPLv2.Core 3.7.4.0 Journal The Journal of Clinical Endocrinology & Metabolism © The Author(s) 2025. 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