Surgery and Medical Treatment in Microprolactinoma: A Systematic Review and Meta-Analysis

Abstract

Objective. Dopamine agonists (DAs) are recommended as the first-line treatment for prolactinomas; however, tumour recurrence after drug withdrawal remains a clinical problem. Recent studies have reported high remission rates via surgery in microprolactinomas. The aim of this systematic review and meta-analysis was to compare the clinical result of DA treatment with surgery as initial therapy in patients with treatment-naive microprolactinoma. Methods. A comprehensive literature search for studies and reports regarding microprolactinoma patients treated with DAs and/or surgery published between January 1970 and November 2020 was conducted using four electronic databases (PubMed, Embase, Google Scholar, and the Cochrane Library). Clinical treatment outcome was evaluated by the biochemical remission of serum prolactin level to normal after treatment. The I2 statistic was used to quantify heterogeneity. Pooled data were analysed according to a random effect model. Results. Eighteen studies with 661 patients were included for analysis. The DA treatment group achieved a higher remission rate at ≥12 months follow-up (96% vs. 86%; P = 0.019 ). Surgery showed a higher remission rate than the DA treatment group after the treatment withdrawal (78% vs. 44%; P = 0.003 ). Patients with preoperative prolactin level of ≤200 ng/mL had a higher remission rate than patients with preoperative prolactin level of >200 ng/mL (92% vs. 40%; P = 0.029 ). Conclusion. Surgery showed a high remission rate in treatment-naive microprolactinoma patients after treatment withdrawal and may be an alternative first-line treatment strategy in addition to DAs, particularly in patients with a preoperative prolactin level of ≤200 ng/mL.

Diagnosis and management of prolactin-secreting pituitary adenomas: a Pituitary Society international Consensus Statement

“…2). This updated Consensus Statement considers new evidence that has markedly influenced clinical practice, including incorporation of transcription factors into pituitary adenoma classification 3 , long-term adverse effects of dopamine agonist therapy 4 , outcomes following dopamine agonist withdrawal 5 and advances in surgical tumour resection [6][7][8][9] . In addition, management during pregnancy [10][11][12] , effects of hyperprolactinaemia on bone and fracture risk 13 , management of cystic and aggressive prolactinomas 14 , and prolactinomas in children and transgender patients are covered.…”

11C-methionine PET aids localization of microprolactinomas in patients with intolerance or resistance to dopamine agonist therapy

“…Not surprisingly, most studies have reported higher remission rates for microprolactinomas compared to macroprolactinomas, and adenomas that are enclosed within the gland may have a more favourable outcome compared with adenomas located at the lateral margins [29,60]. These findings have been endorsed in several systematic reviews and meta-analyses, which have reported TSS to deliver superior clinical outcomes compared to dopamine agonist therapy [19,20,63], with superior costeffectiveness, although the absence of any randomised trials remains a major limitation [19]. Interestingly, one systematic review specifically investigated prolactinoma patients undergoing surgery because of resistance or intolerance to dopamine agonists, or patient preference, and reported that 38% achieved sustained remission without further treatment (66% of microprolactinomas, 22% of macroprolactinomas), while 62% achieved remission with adjunctive dopamine agonist therapy [64].…”

“…This should be distinguished from dopamine agonist resistance, which is preferred when there is failure to normalize serum prolactin and/or achieve significant tumor shrinkage (in macroprolactinomas) despite good tolerance and concordance with standard clinical dosages [17,18]. For patients with intolerance or resistance to medical therapy, transsphenoidal surgery (TSS) is an alternative treatment option [5], with several recent reports suggesting a higher long-term remission rate [19][20][21][22][23][24] and improved cost-effectiveness compared with dopamine agonist therapy [25,26]. As evidence for the efficacy and safety of transsphenoidal surgery (TSS) accrues, there is increasing discussion about the earlier deployment of surgery for selected cases [27,28].…”

Implementation of functional imaging using 11C-methionine PET-CT co-registered with MRI for advanced surgical planning and decision making in prolactinoma surgery

“…For patients with prolactinoma with drug intolerance or resistance, surgery is the next step in the treatment algorithm. Based on recent evidence, surgery is now increasingly considered as a first line treatment option for microprolactinomas and circumscribed macroprolactinomas in which complete resection can be anticipated [2,5,[14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]. With more elective cases being considered for surgery, it becomes more clinically relevant to reliably identify the precise localization of the (remnant) lesion, possible multifocality, and its potential invasion in surrounding structures.…”