Shrinkage by the third month predicts long-term response of macroprolactinoma after cabergoline

Abstract

Objective: Transsphenoidal surgery (TSS) is mainly indicated in prolactinomas when dopamine agonist treatment fails. However, there is no established early predictor of cabergoline (CBG) response. The present study was aimed to identify predictors of CBG resistance in order to select patients who may benefit from early TSS. Design: retrospective longitudinal study Methods: We reviewed the medical record of patients diagnosed with prolactinoma after 2010. Inclusion criteria: macroprolactinomas under CBG treatment with serial prolactin levels and MRI before treatment and 3 and 12 months afterwards. The main outcome was tumour size shrinkage ≥50% after 12 months of CBG (TS_50). The capacity of the most important clinical and biochemical variables in predicting the main outcome was examined. Results: A total of 185 prolactinomas where included: 124 (67.0 %) were microadenomas and 61 (33.0%) were macroadenomas of which 27 patients meet de inclusion criteria; median age [42.5 years; (IQR: 28.0)]. The median of follow up was [67.5 months; (IQR: 30.2)]. Ten patients (37.0%) underwent surgery after more than one year of CBG. The volume reduction at the first MRI (3-4 months) was the unique valuable predictor: [OR: 1.16 (IC 95% 1.02-1.32)] of TS_50. A tumour volume shrinkage ≥30% in the first 3-4 months of CBG therapy predicts TS_50 with an AUC [ 0.95 (CI: 0.76-0.99)]. Conclusion: Tumor shrinkage in the first 3-4 month after starting treatment with CBG is a good tool for predicting the long term response and can help clinicians to take more appropriated and personalized decisions.

Diagnosis and management of prolactin-secreting pituitary adenomas: a Pituitary Society international Consensus Statement

“…Timing after medical therapy. For macroprolactinomas, MRI should be repeated at 3-6 months after the start of dopamine agonist treatment, as a reduction in size at 3 months after starting cabergoline could predict further long-term response and/or biochemical control 72 . For microprolactinomas, re-scanning depends on clinical and biochemical follow-up, but can be repeated after 1 year, or at least when considering withdrawal of dopamine agonists.…”

Molecular Pathways in Prolactinomas: Translational and Therapeutic Implications

“…In this regard, the percentage of prolactin reduction could be a more valuable predictor to response to DAs than a predefined cut-off value [73]. We, and others [82], argue in favour of a direct measure of tumour shrinkage response in the third trimester of treatment as an early marker of tumour response. This strategy permits us to take a more individualised decision and not delay foreseeable successful trans-sphenoidal surgery (TSS) in a subgroup of poor responders to DAs with eventual long-term aggressive behaviour [81].…”

Italian Association of Clinical Endocrinologists (AME) and International Chapter of Clinical Endocrinology (ICCE). Position statement for clinical practice: prolactin-secreting tumors

“…Accordingly, it is worthwhile to begin treatment and monitor PRL values and tumor size. It has been reported that the first PRL values obtained during treatment (either evaluated as absolute value or as percent decrease from baseline or as lowering below a predefined threshold, according to different series) as well as early tumor shrinkage (with different cut-offs in different series) are good predictors of long-term DA efficacy ( 120 ), either evaluated at 6 months ( 121 ) or even earlier ( 122 , 123 , 124 ). On the contrary, it was recently reported but not yet confirmed that heterogeneity of prolactinoma T2 signal at diagnosis could be used as a negative predictor factor of hormonal response to DA ( 87 ).…”