Examining the viability of modern endoscopic endonasal surgery as a first-line treatment for macroprolactinomas: a multicentric study on the results and 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 who have had long-standing symptoms and sought 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 treated with EES over 12 years was retrospectively reviewed. Early surgical results and the determinant factors of outcome were analyzed using a multivariate regression model and Kaplan-Meier curves. RESULTS A total of 76 patients with a mean ± SD age of 42.1 ± 15.6 years and tumor diameter of 22.7 ± 12.1 mm was included. Gross-total resection (GTR) was achieved in 56.6%, with Knosp grade (OR 0.167, CI 0.044–0.633, p = 0.008) and clival invasion (OR 0.119, CI 0.019–0.765, p = 0.025) being the only independent predictors. Short-term remission (52/76 patients [68.4%]) was less frequent in patients with cystic tumors (OR 0.004, CI 0.0001–0.0911, p = 0.04) and was higher in those with intended (OR 36.375, CI 1.627–813.128, p = 0.023) or achieved (OR 32.341, CI 1.487–703.558, p = 0.027) GTR in multivariate analysis. The second half of the learning curve showed early complication rates of 41% versus 16.2% in the first half (p = 0.01). During a mean 47.9 ± 33 months of follow-up, the permanent complication rate was 6.6% and 3/51 patients (5.9%) had recurrence. 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 1 levels (correlation coefficient 0.403, p < 0.001), with final normoprolactinemia rates significantly higher in the GTR group than in the non-GTR group (76.7 vs 45.2%, p = 0.005). DA-resistant/intolerant patients achieved significant prolactin levels reduction (576 to 17 µg/L, p < 0.001), with normal prolactin level in 51.1% of patients and long-term remission in 35.6%. The 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 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). CONCLUSIONS The authors found that modern EES in multidisciplinary centers was a low-morbid option for patients with macroprolactinoma. Remission rates were consistent with those of recent studies with variably sized 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. Radiological criteria alone should not be the sole factor in surgical decision-making.