Aggressive Pituitary Tumors and Pituitary Carcinomas: From Pathology to Treatment

• Published in: The journal of clinical endocrinology and metabolism Vol. 108; no. 7; pp. 1585 - 1601
• Main Authors: Burman, Pia, Casar-Borota, Olivera, Perez-Rivas, Luis Gustavo, Dekkers, Olaf M
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.07.2023
• Subjects: ATRX; Bevacizumab; Bevacizumab - therapeutic use; Brain cancer; Brain tumors; Cabergoline; Cancer; Carcinoma; Chemotherapy; Clinical Laboratory Medicine; Clinical Medicine; Development and progression; Humans; Immune checkpoint inhibitors; Immunosuppressive agents; immunotherapy; Ki67-index; Kinases; Klinisk laboratoriemedicin; Klinisk medicin; Medical and Health Sciences; Medicin och hälsovetenskap; Mini-Review; p53 Protein; Patients; PD-1 protein; Pituitary; Pituitary gland; Pituitary gland tumors; Pituitary Neoplasms - diagnosis; Pituitary Neoplasms - genetics; Pituitary Neoplasms - therapy; PRRT; Radiation therapy; Temozolomide; Temozolomide - therapeutic use; TP53; Tumor proteins; Tumors; Tyrosine; Sweden; temozolomide; PRRT; ATRX; immunotherapy; bevacizumab; TP53; Ki67- index
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/clinem/dgad098

Abstract Aggressive pituitary tumors (APTs) and pituitary carcinomas (PCs) are heterogeneous with regard to clinical presentation, proliferative markers, clinical course, and response to therapy. Half of them show an aggressive course only many years after the first apparently benign presentation. APTs and PCs share several properties, but a Ki67 index greater than or equal to 10% and extensive p53 expression are more prevalent in PCs. Mutations in TP53 and ATRX are the most common genetic alterations; their detection might be of value for early identification of aggressiveness. Treatment requires a multimodal approach including surgery, radiotherapy, and drugs. Temozolomide is the recommended first-line chemotherapy, with response rates of about 40%. Immune checkpoint inhibitors have emerged as second-line treatment in PCs, with currently no evidence for a superior effect of dual therapy compared to monotherapy with PD-1 blockers. Bevacizumab has resulted in partial response (PR) in few patients; tyrosine kinase inhibitors and everolimus have generally not been useful. The effect of peptide receptor radionuclide therapy is limited as well. Management of APT/PC is challenging and should be discussed within an expert team with consideration of clinical and pathological findings, age, and general condition of the patient. Considering that APT/PCs are rare, new therapies should preferably be evaluated in shared standardized protocols. Prognostic and predictive markers to guide treatment decisions are needed and are the scope of ongoing research.