The Association of Postoperative Prolactin Serum Concentration with Recurrence of Prolactinoma

Background While tumor size and postoperative prolactin concentration have been associated with recurrence of prolactinoma following transsphenoidal resection, little modern data exist regarding the role of immediate postoperative prolactin level in the long-term outcome of patients with prolactinoma. Here, we examine the role of immediate postoperative prolactin level on recurrence rates and time to recurrence.

Methods A retrospective cohort study was performed on a consecutive series of 151 patients who were treated surgically for prolactinoma from 2007 to 2014. Surgical indications included failure of medical therapy, intolerance of side effects, cystic tumors, prolactinomas in female patients of childbearing age, and patient preference. Data were collected on patient age, gender, preoperative treatment with dopamine agonist medical therapy, tumor size, invasion, pre- and postoperative serum prolactin concentration, extent of resection, recurrence, and time to recurrence. Biochemical cure was defined as a serum prolactin concentration less than 20 ng/mL on the morning of postoperative day 1, including subgroups with prolactin concentrations < 10 ng/mL (Group 1), 10 to 20 ng/mL (Group 2); failure to achieve remission included patients with a postoperative concentration > 20 ng/mL (Group 3). Recurrence was defined radiographically via MRI as the progression of known residual tumor following primary subtotal resection, or the appearance of new tumor following primary gross total resection. Statistical analysis was performed using chi-square testing, the t-test, and Kaplan–Meier analysis.

Results Of the 151 included patients, there were 49 (32%) men and 102 (68%) women with a median age of 31. The mean tumor size was 1.6 cm; 63 (42%) tumors were microadenomas and 88 (58%) tumors were macroadenomas. Twenty-eight tumors (19%) showed evidence of cavernous sinus invasion on preoperative MRI scans. Preoperative medical therapy was utilized in 86 patients (57%). A gross total resection was achieved in 102 patients (68%) and subtotal resection in 49 patients (32%). Patients were followed up for a mean of 10.5 years, and there were 12 total recurrences (8%) among the 144 patients with available follow-up. Subtotal resection with evidence of immediate biochemical remission was associated with an increased risk of tumor recurrence (p = 0.017, chi-square). Increased postoperative prolactin serum concentration was also associated with an increased risk of tumor recurrence (p < 0.001, t-test), including when substratified by Group 1 (<10 ng/mL), Group 2 (10–20 ng/mL), and Group 3 (> 20 ng/mL) (p = 0.015, t-test). A postoperative prolactin concentration of <10 ng/mL versus 10 to 20 ng/mL did not appear to affect recurrence rates (p = 0.78, t-test). Similarly, when stratified by group number, postoperative prolactin concentration did not appear to affect time until recurrence (p = 0.231, log rank).

Conclusion Our modern case series of surgically treated prolactinoma patients supports an association between biochemical remission (postoperative prolactin serum concentration < 20 ng/mL) and decreased recurrence rate, but there does not appear to be a difference in recurrence rate of greater or less than 10 ng/mL between patients. Modern surgical techniques overall offer durable long-term results with low recurrence rates.