2025 Proffered Presentations
S169: CLINICAL AND IMAGING FINDINGS SUGGEST CLONAL RESISTANCE TO DOPAMINE AGONIST THERAPY IN A SUBSET OF MEDICALLY REFRACTORY PROLACTINOMAS
David Peters, MD; Yuki Shinya; Jamie Van Gompel; Mayo Clinic
Introduction: Prolactinomas are the most common type of functioning pituitary tumors. The primary line of treatment for prolactinomas is typically medical management with dopamine agonists (DAs), which suppress prolactin secretion and induce tumor shrinkage/senescence. This approach is highly effective in most cases, rendering surgery unnecessary for many patients. However, a subset of patients exhibit resistance to DAs, posing a significant clinical challenge.
Clonal resistance is a well described phenomenon for several types of cancer where certain subpopulations, or "clones," of tumor cells acquire genetic or epigenetic changes that allow them to resist treatment. Tumors are often heterogeneous cell populations that can evolve over time due to selective pressures, such as drug exposure. However, clonal resistance in response to DA therapy has not yet been described as a mechanism of medical failure in prolactinomas.
This study reviewed all surgically treated prolactinomas at a large institution, focusing on cases where medical therapy failed due to potential clonal vs global resistance. We aim to provide insights into optimizing treatment strategies for this challenging subset of prolactinoma patients.
Methods: A retrospective single institution analysis was conducted on all patients with prolactinomas that underwent surgical resection between 2012-2022. Imaging, clinical data, surgical indications were reviewed.
Results: 69 patients were identified who underwent endoscopic transsphenoidal resection for a pituitary lesion and had pathological diagnosis of prolactinoma. 37 patients had elected surgical resection after inability to tolerate DA medications. 4 patients elected surgery due to acute vision loss. 17 patients had no significant response on imaging or with prolactin levels to DA therapy. 11 patients showed an initial good response to DA therapy with normalization of prolactin levels and significant tumor shrinkage, but then developed a focal recurrence that became resistant to further DA therapy and necessitated surgical intervention.
Conclusion: The imaging and clinical history in this series of patients suggests that clonal resistance is potentially one possible mechanism of medical failure for DA therapy of prolactinomas. Molecular and genetic analyses are needed to confirm these preliminary findings.