Surgery as a Viable Alternative First-Line Treatment for Prolactinoma Patients. A Systematic Review and Meta-Analysis

Abstract

Context The improved remission and complication rates of current transsphenoidal surgery warrant reappraisal of the position of surgery as a viable alternative to dopamine agonists in the treatment algorithm of prolactinomas. Objective To compare clinical outcomes after dopamine agonist withdrawal and transsphenoidal surgery in prolactinoma patients. Methods Eight databases were searched up to July 13, 2018. Primary outcome was disease remission after drug withdrawal or surgery. Secondary outcomes were biochemical control and side effects during dopamine agonist treatment and postoperative complications. Fixed- or random-effects meta-analysis was performed to estimate pooled proportions. Robustness of results was assessed by sensitivity analyses. Results A total of 1469 articles were screened: 55 (10 low risk of bias) on medical treatment (n = 3564 patients) and 25 (12 low risk of bias) on transsphenoidal surgery (n = 1836 patients). Long-term disease remission after dopamine agonist withdrawal was 34% (95% confidence interval [CI], 26-46) and 67% (95% CI, 60-74) after surgery. Subgroup analysis of microprolactinomas showed 36% (95% CI, 21-52) disease remission after dopamine agonist withdrawal, and 83% (95% CI, 76-90) after surgery. Biochemical control was achieved in 81% (95% CI, 75-87) of patients during dopamine agonists with side effects in 26% (95% CI, 13-41). Transsphenoidal surgery resulted in 0% mortality, 2% (95% CI, 0-5) permanent diabetes insipidus, and 3% (95% CI, 2-5) cerebrospinal fluid leakage. Multiple sensitivity analyses yielded similar results. Conclusions In the majority of prolactinoma patients, disease remission can be achieved through surgery, with low risks of long-term surgical complications, and disease remission is less often achieved with dopamine agonists.

First-line surgery in prolactinomas: lessons from a long-term follow-up study in a tertiary referral center

“…While consensus guidelines recommend dopamine agonists (DAs) as the first-line approach in the treatment of prolactinomas, [1][2][3][4] surgery is primarily indicated in patients who are resistant to or intolerant of DAs, in cases of cystic adenomas, or intratumoral hemorrhage with persisting visual disturbances [5][6][7][8][9][10][11]. Thus, most surgical series report the results of a second-line approach in patients with evidence of resistance or intolerance to DAs [5,12].…”

“…The renewed acceptance of surgical treatment of prolactinomas, however, primarily applies to patients with a microprolactinoma, in whom a short-term cure rate of about 90% can be anticipated [27][28][29][30][31]. However, the indication for upfront surgery in macroprolactinomas remains controversial, and long-term data on patients in large cohorts is limited [8,[32][33][34].…”

Prolactinomas: Prognostic Factors of Early Remission After Transsphenoidal Surgery

“…Previous studies suggested that men, elderly patients, patients with large, invasive, or highly proliferating tumors, and patients with high post-operative prolactin concentrations or previous incomplete resections are less likely to achieve remission after surgical removal of prolactinomas ( 14 – 19 ). However, predicting outcomes of prolactinoma resection based on the available evidence remains difficult ( 20 ). Therefore, we analyzed which of the selected clinical, imaging, pathological, and hormonal characteristics were associated with early remission after transsphenoidal removal of prolactinomas in our patients.…”

Healthcare utilization and costs among prolactinoma patients: a cross-sectional study and analysis of determinants

“…Dopamine agonists (DA) are the first-line treatment for most patients [ 6 ]. While these are highly effective and generally well tolerated [ 7 ], side effects may occur [ 8 ], most frequently fatigue (30%), libido changes (28%), and sleep disorders (25%) [ 9 ]. Moreover, particularly psychological side effects (e.g., depressive symptoms and behavioral changes) are considered to be underreported [ 10 ].…”

“…Moreover, particularly psychological side effects (e.g., depressive symptoms and behavioral changes) are considered to be underreported [ 10 ]. Medical treatment may be temporary, although recent reviews have shown lower remission rates than previously thought (21–36.6%) [ 9 , 11 , 12 ], suggesting the need for long-term medical treatment [ 11 , 12 ], including ongoing follow-up by endocrinologists and other healthcare professionals [ 6 ]. In case of resistance or intolerance to medical therapy, and depending on patient preference, transsphenoidal selective adenomectomy can be considered as alternative treatment option [ 6 , 13 ].…”