European Society of Endocrinology Clinical Practice Guidelines for the management of aggressive pituitary tumours and carcinomas

Abstract

Background: Pituitary tumours are common and easily treated by surgery or medical treatment in most cases. However, a small subset of pituitary tumours does not respond to standard medical treatment and presents with multiple local recurrences (aggressive pituitary tumours) and in rare occasion with metastases (pituitary carcinoma). The present European Society of Endocrinology (ESE) guideline aims to provide clinical guidance on diagnosis, treatment and follow-up in aggressive pituitary tumours and carcinomas. Methods: We decided upfront, while acknowledging that literature on aggressive pituitary tumours and carcinomas is scarce, to systematically review the literature according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. The review focused primarily on first-and second-line treatment in aggressive pituitary tumours and carcinomas. We included 14 single-arm cohort studies (total number of patients = 116) most on temozolomide treatment (n = 11 studies, total number of patients = 106). A positive treatment effect was seen in 47% (95% CI: 36-58%) of temozolomide treated. Data from the recently performed ESE survey on aggressive pituitary tumours and carcinomas (165 patients) were also used as backbone for the guideline. In patients responding to first-line temozolomide, we suggest continuing treatment for at least 6 months in total. Furthermore, the guideline offers recommendations for patients who recurred after temozolomide treatment, for those who did not respond to temozolomide and for patients with systemic metastasis.

Hyperprolactinaemia

“…DA resistance occurs in approximately 20 to 30% of patients on bromocriptine and around 10% of patients on cabergoline [109]. Male sex, younger age at diagnosis, tumour invasiveness (particularly in the cavernous sinus) and size >4 cm have been proposed as clinical factors associated with DA resistance [109,112]. In such cases, switching bromocriptine to cabergoline is an option, leading to normalization of PRL in 80 to 85% of patients [109].…”

Pituitary carcinoma: The University of Texas MD Anderson Cancer Center experience

“…32, 33 The 2017 European guideline for pituitary tumors encourages testing of MGMT expression by IHC on aggressive pituitary tumors and pituitary carcinomas (even though only a minority of them exhibit homogenous MGMT expression), as it may help predict treatment success with temozolomide, the first-line chemotherapy recommended for such tumors. 22, 34 Nevertheless, MGMT may not be the sole driver for susceptibility to TMZ, and other enzymes, such as MSH6, may also contribute to PC sensitivity to alkylating agents. 25 For this reason, caution is warranted when using MGMT expression as the only criterion to decide on the use of temozolomide in PC and locally aggressive PA, as both lack of response in patients with low expression and favorable response in patients with high expression have been described.…”

The Genetics of Pituitary Adenomas

“…TP53 codes for a tumor suppressor protein that has important implication in human carcinogenesis. Although p53 expression in pituitary tumors is associated with more aggressive behavior, several studies have failed to show a significant role of genetic defects of TP53 in pituitary tumorigenesis [119][120][121]. Few cases of atypical PAs and pituitary carcinomas with somatic TP53 defects have only been reported to date [122][123][124].…”