2025 Proffered Presentations
S165: EFFECT OF PREOPERATIVE MEDICAL TREATMENT ON TUMOR FIBROSIS AND SURGICAL OUTCOMES IN PROLACTINOMAS
Vladimir A Ljubimov, MD; Taishi Nakase, MS; Julia J Chang, MD; Hannes Vogel, MD; Vera Vigo, MD; Juan C Fernandez-Miranda, MD; Stanford University
Introduction: With advances in endoscopic endonasal surgery (EES), prolactinoma resection can provide definitive cure. Conversely, many patients with hyperprolactinemia can be treated with dopamine agonists (DA) without the risk of surgical complications. The effects of preoperative DA therapy on tumor consistency and surgical outcomes are still debated, with conflicting conclusions based on medication type, tumor size and outcome measure. Critically, most previous studies on DA-induced tumor fibrosis have examined the historic use of bromocriptine rather than cabergoline, which is the preferred drug in current practice. We aimed to examine how medication type and tumor size modulate the effect of preoperative DA therapy on tumor fibrosis, surgical morbidities and biochemical remission.
Methods: We retrospectively reviewed medical records of 57 consecutive patients (23 males, median 37 years) who underwent EES for prolactinoma resection at a single center from 2018 to 2024. Sixteen patients received primary surgery and 41 patients received surgery after DA therapy, with similar proportions of macroadenomas (75% vs. 59%, P=0.39) and cavernous sinus invasion (19% vs. 24%, P=0.92).
Results: Tumor fibrosis based on intraoperative assessment (Figure 1) was as common in cabergoline-pretreated patients as in primary surgery patients (39% vs. 31%, P=0.64; Figure 2A), whereas bromocriptine exposure was correlated with a borderline significant increase in tumor fibrosis compared to bromocriptine-naive patients (60% vs. 36%, P=0.10; Figure 2B). Despite longer surgical duration (336 ± 126 minutes vs. 247 ± 75 minutes, P=0.01), cabergoline-pretreated patients were more likely to experience normalization of prolactin (PRL) levels within three days after surgery (92% vs. 58%, P=0.03; Figure 3A) and have similar long-term remission rates (85% vs. 88%, P=1.00; Figure 3B) compared to primary surgery patients. Patients with fibrous macroadenomas had marginally lower rates of initial postoperative remission (64.3% vs. 77.8%, P=0.45) and long-term postoperative remission (57.1% vs. 77.3%, P=0.27) than patients with non-fibrous tumors, although these differences did not achieve statistical significance. All patients with microadenomas regardless of tumor consistency achieved long-term remission.
Conclusion: Our study showed that DA-induced prolactinoma fibrosis is a concern for bromocriptine rather than cabergoline. While DA-pretreatment may increase surgical duration, it does not result in inferior biochemical outcomes. Critically, we note that preoperative cabergoline therapy should not be considered an impediment to later surgery when it is performed by an experienced pituitary surgeon. Fibrous macroadenomas, however, may interfere with biochemical remission, emphasizing the need to develop tools that preoperatively identify tumor fibrosis and assist surgical planning.
Figure 1: Examples of fibrous and non-fibrous prolactinomas. H&E stained tissue (magnification x100) from non-fibrous (A) and fibrous tumors (D). Endoscopic endonasal perspective from non-fibrous (B, C) and fibrous (E, F) tumors (green circle).
Figure 2: Tumor consistency of prolactinomas stratified by preoperative treatment. BROM=bromocriptine. CAB=cabergoline.
Figure 3: Preoperative DA treatment and biochemical remission. (A) Initial postoperative remission. (B) Long-term postoperative remission. Patients were grouped based on their most recent follow-up visit: complete biochemical remission (Remission), medically-managed biochemical remission (Normal PRL on DA) and persistent hyperprolactinemia (High PRL).
