Examining the Viability of Endoscopic Endonasal Surgery as an Early Treatment Strategy for Macroprolactinomas: The Significance of the Highest Preoperative Prolactin Level in Predicting Long-Term Surgical Outcomes

Objective: As modern endoscopic endonasal surgery (EES) becomes increasingly refined, patients with large prolactinomas may seek alternatives to lifelong dopamine-agonist (DA) therapy. This may raise interest in reassessing potential treatment paradigms and surgical outcomes, particularly in patients with larger tumors who may suffer long-standing compressive symptoms and seek a more definitive solution. The objective of this study was to explore the viability of EES in experienced centers as a reliable alternative to managing macroprolactinomas.

Methods: A multicentric cohort of patients with histologically proven macroprolactinoma (diameter ≥ 10 mm) treated by EES over 12 years at three academic tertiary centers was retrospectively reviewed. Medical records were examined for endocrine, radiologic, and surgical characteristics. Data curation was blinded to outcomes. Early surgical results and the determinant factors of outcome were analyzed using multivariate regression model and Kaplan–Meier curves.

Results: A total of 76 patients (45 males, 31 females) with a mean age of 42.1 ± 15.6 years and tumor diameter of 22.7 ± 12.1 mm was included. Gross total resection was achieved in 56.6%, with the Knosp grade (OR = 0.167, 95% CI: 0.044–0.633, p = 0.008) and clival invasion (OR = 0. 119, 95% CI: 0.019–0.765, p = 0.025) being the only independent predictors. Third ventricle invasion was significantly associated with postoperative CSF leak (1.3%) and permanent DI (2.6%). Short-term remission, observed in 52 patients (71.2%), was less frequent in cystic tumors (OR: 0.04, CI: 0.0001–0.0911, p = 0.04) and higher in intended (OR: 36.375, CI: 1.627–813.128, p = 0.023) or achieved GTR (OR: 32.341, CI: 1.487–703.558, p = 0.027) in multivariate analysis. During a mean 47.9 ± 33 months of follow-up, permanent complication rates were 6.6%, and three patients (5.9%) recurred. Overall 4-year recurrence-free survival was significantly lower in DA-dependent patients (70 vs. 100%, p < 0.001). Last follow-up prolactin levels were positively correlated with postoperative day one levels (correlation coefficient = 0.403, p < 0.001). The rate of normoprolactinemia at the last follow-up was significantly higher in the GTR group than the non-GTR group (76.7 vs. 45.2%, p = 0.005). DA-resistant/intolerant patients achieved significant prolactin levels reduction (576–17 μg/L, p < 0.001), with normal prolactin level in 51.1%, and long-term remission in 35.6% of patients. Overall long-term DA-free remission rate was 39.3%, with the highest preoperative prolactin level (OR: 0.999, CI: 0.996–0.998, p = 0.042) being the only independent predictor of the failure. Subgroup analysis showed remission rates of 80 versus 23.9% in patients with the highest preoperative prolactin levels <150 versus ≥150 µg/L, respectively (p < 0.001).

Conclusion: We found EES in multidisciplinary centers a low-morbid option for patients with macroprolactinomas. Remission rates were consistent with recent studies with variable-size prolactinomas, and recurrence rates were low. Although not universally definitive for macroprolactinomas, early EES can be offered for patients with the highest preoperative prolactin levels below 150 μg/L who are unwilling to receive long-term medication. Radiologic criteria alone should not be the sole factor in surgical decision-making.

Publication History

Article published online:
07 February 2025