Aggressive pituitary tumors and pituitary carcinomas: Definition, management, and overview for clinical practice.

Background: Aggressive pituitary tumors and pituitary Carcinomas (PCs) represent very uncommon entities within the field of pituitary diseases. Unfortunately, treatment options after progression on temozolomide are limited. However, advances in the understanding of pituitary tumor genetics and their immunological landscape are paving the way for new targeted molecular therapies. Methods: In this article, we present an overview of the most recent literature, focusing on the specificities and role of current treatments and future perspectives in the management of these lesions. Results and Conclusions: Aggressive pituitary tumors and PCs remain very challenging conditions requiring a specific multidisciplinary approach in Pituitary Tumor Centers of excellence. If standard therapy fails, Temozolomide represents the first-line treatment option. Peptide Receptor Radionuclide Therapy may be also considered, especially in tumors expressing specific Somatostatin receptors. When tumors progress after Temozolomide treatment, the prognosis is typically poor, and among the various second-line treatment options immune checkpoint inhibitors have proven to be the most effective. Further studies exploring new potential targeted therapies and predictive factors for pituitary tumor aggressiveness are now essential to improve the management and outcomes for these patients.