SAT-124 - Clinical Profile and Outcomes of Surgically Treated Prolactinomas

Background: Dopamine agonists (DA) are recommended as first-line therapy for prolactinomas due to high rates of prolactin normalization and tumor shrinkage. Surgery is reserved for patients with resistance or intolerance to medical therapy, although it may be considered as an initial strategy in selected cases with mass effect/compressive symptoms. Real-world data on surgically treated prolactinomas remain limited.
Method and results: We retrospectively analyzed prolactinoma patients undergoing pituitary surgery at a tertiary center (1993–2025). Eighteen patients were included, predominantly male (13/18, 72%) with median age at diagnosis and at surgery 33 and 34 yrs-old, respectively. All tumors were macroprolactinomas, mean maximal diameter of 48mm (17-76), consistent with invasive disease. Mean PRL levels at diagnosis was 2,389ng/mL, remaining markedly elevated before surgery (mean 2,011ng/mL). Eight patients (44%) underwent surgery after DA therapy (BRC, n = 2 – dose 15mg/d; CAB, n = 6 – dose 1-7mg/w) for a mean follow-up of 21 months (0.4–48) due to resistance (n=4), intolerance (n=3) and liquoric fistula with debulking tumor (n=1), while ten (56%) had surgery as first-line treatment for apoplexy (n=2), cystic tumor (n=1), mass effect with neurologic symptoms (n=5) or surgeon preference (n=2). Immunohistochemistry confirmed prolactin expression in all tumors; two showed LH/FSH co-expression, consistent with plurihormonal PitNETs, which may be associated with larger tumor size, increased biological heterogeneity, and reduced responsiveness to DA therapy. Mean Ki-67 index analyzed in 15 patients was 4.2%, with bimodal distribution with peaks at 0.5% and 2.0%. Despite the invasiveness, most tumors (66%) exhibited low proliferative activity (Ki-67 < 3%), whereas a subset (n=2) displayed markedly elevated Ki-67 values (>20%), consistent with a more aggressive biological behavior as described in the literature. Postoperatively, one patient achieved complete biochemical remission without adjuvant therapy. Among 14 patients treated with DA, two achieved remission, six maintained PRL normalization with low-dose CAB, two required radiotherapy, and four had persistent hyperprolactinemia despite CAB. Hypopituitarism was observed in 13 patients and diabetes insipidus in three patients (one permanent). No perioperative mortality was observed.

Conclusion: In this long-term real-world cohort, surgically treated prolactinomas represent a heterogeneous subgroup, characterized by male predominance, large invasive tumors, high PRL levels, and DA resistance. Surgery improved biochemical control however was rarely curative without adjuvant therapy and was associated with significant postoperative endocrine morbidity, reinforcing the need for careful patient selection and underscore the complexity of managing prolactinomas requiring surgical intervention.

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