Aggressive pituitary tumours and carcinomas, characteristics and management of 171 patients

Eur J Endocrinol. 2022 Sep 19;187(4):593-605. doi: 10.1530/EJE-22-0440. Print 2022 Oct 1.

Abstract

Objective: To describe clinical and pathological characteristics and treatment outcomes in a large cohort of aggressive pituitary tumours (APT)/pituitary carcinomas (PC).

Design: Electronic survey August 2020-May 2021.

Results: 96% of 171 (121 APT, 50 PC), initially presented as macro/giant tumours, 6 were microadenomas (5 corticotroph). Ninety-seven tumours, initially considered clinically benign, demonstrated aggressive behaviour after 5.5 years (IQR: 2.8-12). Of the patients, 63% were men. Adrenocorticotrophic hormone (ACTH)-secreting tumours constituted 30% of the APT/PC, and the gonadotroph subtypes were under-represented. Five out of 13 silent corticotroph tumours and 2/6 silent somatotroph tumours became secreting. Metastases were observed after median 6.3 years (IQR 3.7-12.1) from diagnosis. At the first surgery, the Ki67 index was ≥3% in 74/93 (80%) and ≥10% in 38/93 (41%) tumours. An absolute increase of Ki67 ≥ 10% after median of 6 years from the first surgery occurred in 18/49 examined tumours. Tumours with an aggressive course from outset had higher Ki67, mitotic counts, and p53. Temozolomide treatment in 156/171 patients resulted in complete response in 9.6%, partial response in 30.1%, stable disease in 28.1%, and progressive disease in 32.2% of the patients. Treatment with bevacizumab, immune checkpoint inhibitors, and peptide receptor radionuclide therapy resulted in partial regression in 1/10, 1/6, and 3/11, respectively. Median survival in APT and PC was 17.2 and 11.3 years, respectively. Tumours with Ki67 ≥ 10% and ACTH-secretion were associated with worse prognosis.

Conclusion: APT/PCs exhibit a wide and challenging spectrum of behaviour. Temozolomide is the first-line chemotherapy, and other oncological therapies are emerging. Treatment response continues to be difficult to predict with currently studied biomarkers.

MeSH terms

  • Adenoma* / pathology
  • Adrenocorticotropic Hormone / metabolism
  • Bevacizumab / therapeutic use
  • Carcinoma* / drug therapy
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Ki-67 Antigen / metabolism
  • Male
  • Pituitary Neoplasms* / pathology
  • Radioisotopes / therapeutic use
  • Receptors, Peptide / metabolism
  • Temozolomide / therapeutic use
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Immune Checkpoint Inhibitors
  • Ki-67 Antigen
  • Radioisotopes
  • Receptors, Peptide
  • Tumor Suppressor Protein p53
  • Bevacizumab
  • Adrenocorticotropic Hormone
  • Temozolomide