Surgery as a first-line option for prolactinomas

[madman]

Surgery as a first-line option for prolactinomas (2022)
Adam Mamelak


ABSTRACT

Introduction: Treatment of prolactinomas with dopamine agonists has been the established first-line treatment option for many years, with surgery reserved for refractory cases or medication intolerance. This approach may not be the best option in many cases.

Areas covered: Review of the epidemiology, biology, and treatment options available for prolactinomas, including the best available data on outcomes, costs, and morbidities for each therapy. These data are then used to propose a ‘surgery-first’ treatment approach for a subset of prolactinomas as an alternative to primary medical management.

Expert opinion: Based on the available data, there is a strong rationale that transsphenoidal surgery should be considered a first-line treatment option for both micro- and macro-prolactinomas that do not demonstrate high-grade cavernous sinus invasion on MRI imaging, with dopamine agonists administered as a secondary therapy for tumors not in remission following surgery, and for giant tumors. This ‘surgery-first’ approach assumes the availability of skilled and experienced pituitary surgeons to ensure optimal outcomes. This approach should result in high cure rates and reduced DA requirements for patients not cured from the initial surgery. Further, it will reduce medical costs over a patient’s lifetime and the chronic morbidities associated with protracted dopamine agonist usage.




1. Introduction

Despite prolactinoma being the most common hormone-secreting pituitary tumor [1], it is often among the least commonly operated, ranging from 7% to 20% of tumors in several large series [2–5]. This observation is historically attributed to both the efficacy of non-surgical treatment by dopamine agonists (DA) as well as a prevalence for later-term recurrence following initial remission. The goal of this review is to reevaluate the most current data on this topic and determine if indeed the role for surgery has been underestimated.




2. Epidemiology and clinical presentation


3. Overview of prolactin biology


4. Causes of hyperprolactinemia


5. Treatment options

5.1. Observation

5.2. Dopamine agonists
5.2.1. Bromocriptine
5.2.2. Cabergoline

5.3. Dopamine agonist side effects

5.4. Withdrawal of dopamine agonists

5.5. Dopamine resistance


6. Surgery


7. Cost of surgical versus medical therapy


8. Radiation therapy


9. Expert opinion




10. Conclusion

There is currently relative equivalency between the outcomes of transsphenoidal surgery and medical therapy for prolactinomas without high-grade cavernous sinus invasion. Assuming there is an experienced, and competent pituitary neurosurgeon available, surgical therapy should no longer be relegated to second-line therapy in appropriately selected cases, and in fact, should be considered a first-line option offered to patients upfront. A prospective randomized trial comparing primary surgical and primary medical therapy would be the ideal way to resolve this issue. As a shift toward primary surgery occurs, careful reevaluation of data will prove invaluable to make a final determinant of the benefits of each approach.

 

[madman]

Table 1. Complications of transsphenoidal surgery for pituitary tumors*.

*From the author’s personal series of 897 pituitary adenomas [19]. Results are like those reported by other series [106]

 

[Nelson Vergel]

Ummm...nope!

I would try to take cabergoline fist to shrink it unless my vision is affected.

 

[madman]

Figure 1. Knosp Grading Scale for determining the extent of cavernous sinus invasion by pituitary tumors. Grade 0–2 tumors are considered not invasive of the cavernous sinus. Grade 3–4 tumors are considered invasive. Grade 3 is frequently subdivided into grade 3A (above the inferior aspect of the intra-cavernous carotid artery) and 3B (below the inferior aspect of the intra-cavernous carotid artery). The Knosp grading schema is well-validated and has proven to be a strong predictor of the extent of surgical resection for pituitary adenomas. Grade 4 tumors are rarely able to be totally removed, while grade 0–2 tumors have a high rate of total removal by experienced surgeons. Results for Grade 3 are more variable (see text for details). © Giovanna Santoni, CMI. Used by permission.

 

[madman]

 

[madman]

Figure 2. Proposed decision-making algorithm for first-line surgical approach. In this schema, Knosp grade is used as the primary determinant of whether surgery should be considered an initial treatment option.

 

[madman]

Figure 3. A) Intrasellar (Knosp grade 0) micro-prolactinoma. This 36-year-old female presented with secondary amenorrhea, headaches, and a PRL level of 95 ng/ml. She did not tolerate even low doses of cabergoline. B) Surgery was carried out demonstrating total removal at 3 months. An immediate post-operative PRL level was 1.7 ug/L which remained in the normal range with no medication with a resumption of normal menses and resolution of headaches.

 

[madman]

Figure 4. A) Macroprolactinoma with grade 3 cavernous sinus invasion. A 26-year-old male presented with hypogonadism and headaches. The initial prolactin level was 2248 ng/ml. Despite increasing doses of cabergoline and some tumor shrinkage (B), prolactin never normalized. He subsequently underwent surgery where prominent fibrosis and hemorrhage were noted. Postoperative PRL was 31 ng/ml and he his PRL level has remained normal on cabergoline 0.5 mg weekly.

 

[madman]

Figure 5. A) Giant prolactinoma in an 18-year-old male with serum prolactin > 20,000 ng/ml, bitemporal hemianopsia, and hypopituitarism. MRI demonstrates a large mass with bilateral Grade 4 cavernous sinus invasion. B) Treatment with cabergoline resulted in the normalization of prolactin and massive tumor regression with the restoration of vision in 6 weeks. No surgery was performed. It is unlikely initial surgical resection would have benefitted the patient.

 

[madman]

Article highlights

● Dopamine agonists are established first-line therapy for the treatment of prolactinomas

● Prolactin levels are normalized in 73–96% of patients treated with dopamine agonists, and tumor shrinkage is observed in 47–97%

● Long-term dopamine agonist withdrawal after prolactin normalization is accomplished in only 16–21% of patients, often leading to protracted or even life-long use

● Transsphenoidal surgical cure rates for microadenomas range from approximately 65–93% (up to 100% in some reports), and for macroadenomas approximately 45–60%, with patients in both groups who were not cured requiring less DA to achieve long-term remission

● Transsphenoidal surgery for prolactinoma is very safe, with new hormonal deficiencies reported in less than 3% of patients, and major morbidity and mortality below 1%

● Extent of cavernous sinus invasion, not tumor size, is the single most important independent primary predictor of surgical remission, with high rates of remission in tumors with low-grade cavernous sinus invasion

● Transsphenoidal surgery may be a more cost-effective, easier, and equally effective treatment for prolactinomas without cavernous sinus invasion. It should be considered a first-line treatment in appropriate situations and when expert pituitary surgery is available