Cure and Hormonal Control After Prolactinoma Resection

Case Series and Systematic Review

Marisa C. Penn; Tyler Cardinal; Yanchen Zhang; Brittany Abt; Phillip A. Bonney; Patricia Lorenzo; Michelle Lin; Jack Rosner; Martin Weiss; Gabriel Zada; John D. Carmichael

Disclosures

J Endo Soc. 2021;5(10)

Conclusions

This retrospective series of 56 prolactinoma patients treated surgically at a tertiary pituitary center suggests that surgical resection can be an effective treatment for prolactinoma patients. CSI status, tumor size, POD1 prolactin levels, and EOR can be used to predict surgical cure. In particular, POD1 prolactin levels greater than 7.6 ng/mL can reliably predict that a patient will not attain surgical cure. We suggest that significant preoperative prolactin elevations (> 500 ng/mL for surgical cure and > 1000 ng/mL for biochemical control regardless of postoperative DA therapy) may decrease the likelihood of surgical cure or biochemical control irrespective of DA therapy. Although surgical resection of prolactinomas is safe at experienced pituitary centers, it should be reserved for selected cases in which patients can achieve disease control, relief of symptoms of mass effect, or reduction of DA dosage. Realistic outcomes regarding biochemical control and ongoing dependence on medications should be provided to patients to aid in decision making.

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Abbreviations
CSI, cavernous sinus invasion; DA, dopamine agonist; DI, diabetes insipidus; EMR, electronic medical record; EOR, extent of resection; GTR, gross total resection; MRI, magnetic resonance imaging; POD, postoperative day; SRS, stereotactic radiosurgery; STR, subtotal resection; TSSR, transsphenoidal surgical resection; USC, University of Southern California.

Additional Information
Data Availability
Restrictions apply to the availability of some or all data generated or analyzed during this study to preserve patient confidentiality or because they were used under license. The corresponding author will on request detail the restrictions and any conditions under which access to some data may be provided.

Table 1. Overview of presenting patient and tumor characteristics
Patient characteristic	No. (%)
Female	40 (71%)
Male	16 (29%)
Age at surgery, mean ± SD, y	35.6 ± 13.3
Mean clinical follow-up time, mo	39.4 ± 42.1
Mean neuroimaging follow-up time, mo	33.3 ± 36.2
Type of surgical resection
Endoscopic endonasal transsphenoidal	19 (34%)
Microscopic endonasal transsphenoidal	37 (66%)
Presenting symptoms
Amenorrhea/oligomenorrhea	34 (61%)
Galactorrhea	19 (34%)
Headache	25 (45%)
Visual loss	11 (20%)
Decreased libido	11 (20%)
Fatigue	8 (14%)
Dizziness	5 (9%)
Prior treatment
Prior DA therapy	47 (84%)
Prior transsphenoidal resection	6 (11%)
No prior treatment	9 (16%)
Neuroimaging characteristics
Maximal tumor diameter, cm	1.6 ± 0.86
Macroadenomas	40 (73%)
Microadenomas	15 (27%)
Giant prolactinoma	1 (2%)
Suprasellar extension	24 (43%)
Sphenoid sinus invasion	9 (16%)
Clival extension	1 (2%)
Cavernous sinus invasion	20 (36%)
Purely intrasellar	15 (27%)

Abbreviation: DA, dopamine agonist.

Table 2. Postoperative outcomes and adjuvant therapy
Postoperative complications	No. (%)
Transient DI	4 (7)
Hyponatremia	3 (5)
CSF leak	3 (5)
Epistaxis	2 (4)
Meningitis	2 (4)
Surgical outcomes
Gross total resection	25 (49)
Subtotal resection	26 (51)
Tumor progression	5 (9)
Tumor recurrence	3 (5)
Hormonal outcomes
Surgical cure	25 (46)
Biochemical control	35 (64)
Adjuvant therapy
DA therapy	14 (25)
SRS	5 (9)
DA therapy + SRS	5 (9)
DA therapy + additional resection	1 (2)
DA therapy + SRS + additional resection	1 (2)

Abbreviation: CSF, cerebrospinal fluid; DA, dopamine agonist; DI, diabetes insipidus; SRS, stereotactic radiosurgery.

Table 3. Comparison of male and female patients
	Male (n = 16)	Female (n = 40)	95% CI	P
Mean age at time of surgery, y	45.8	31.6	–21.2 to −7.3	< .001^a
Preoperative prolactin, ng/mL	307 ± 798	231 ± 388	–436 to 285	.675^a
Mean maximal tumor diameter, mm	2.2cm	1.4cm	–1.4 to −0.28	.004^a
Suprasellar extension	9 (56%)	23 (56%)	–	.932^b
Cavernous sinus invasion	8 (50%)	28 (70%)	–	.158^b
Purely intrasellar	13 (81%)	28 (70%)	–	.39^b
Postoperative d 1 prolactin	46 ± 76	62 ± 112	–55 to 87	.652^b
Gross total resection	5 (31%)	20 (50%)	–	.148^b
Surgical cure	3 (19%)	22 (57%)	–	.011^b
Biochemical control	8 (50%)	27 (68%)	–	.178^b

^aIndependent samples t test.
^bChi-square analysis 95% CI.

Table 4. Comparison of patients with and without surgical cure and patients with and without biochemical control
	Surgical cure (n = 25)	No surgical cure (n = 30)	P, 95% CI	Biochemical control (n = 35)	Nonbiochemical control (n = 20)	P, 95% CI
Sex	3 (12%) male, 22 (88%) female	13 (43%) male, 17 (57%) female	.011^b	8 (23%) male, 27 (77%) female	8 (40%) male, 12 (60%) female	.178^b
Mean age at surgery, y	33.3 ± 13	37.7 ± 13.6	.228^a, −2.8 to 11.7	36.3 ± 14	34.5 ± 12.7	.63^a, –9.4 to 5.8
Prior transsphenoidal resection	0 (0%)	6 (20%)	.018^b	1 (3%)	5 (25%)	.011^b
Mean preoperative prolactin level, ng/mL	96.7 ± 96.9	361 ± 658	.054^a, −4.8 to 533	89.3 ± 38.3	512 ± 776	.04^a,22.8 to 823
Mean postoperative d 1 prolactin level, ng/mL	4.7 ± 4.1	95.5 ± 122.5	.001^a, 39 to 143	19.3 ± 36.4	125 ± 144	.014^a,25 to 186
Maximal diameter, cm	1.3 ± 7.3	1.9 ± 9.2	.028^a, 0.064 to 1.1	1.4 ± 0.72	2.0 ± 1.1	.042^a,0.02 to 1.1
Suprasellar extension	8 (32%)	16 (53%)	.11^b	13 (37%)	11 (55%)	.20^b
Cavernous sinus invasion	3 (12%)	17 (57%)	.001^b	12 (34%)	8 (40%)	.67^b
Purely intrasellar	11 (44%)	3 (10%)	.004^b	11 (31%)	3 (15%)	.18^b
Gross total resection(n = 50)	18 (90%)	2 (10%)	< .001^b	21 (70%)	9 (30%)	< .001^b

^aIndependent samples t test.
^bChi-square analysis 95% CI.

Table 5. Systematic review of series reporting outcomes after surgical resection of prolactinomas
Study authors	No.	% Female	No. of patients achieving hormonal remission			Criteria for hormonal remission	Follow-up time, mo	Prognostic variables
Study authors	No.	% Female	Micro (%)	Macro (%)	All (%)	Criteria for hormonal remission	Follow-up time, mo	Prognostic variables
Ogiwara et al	5	60.00	5/5 (100%)	–	100%	Surgical w/chemical cure	Mean: 3	Preoperative prolactin levels, tumor size, cavernous sinus invasion, previous treatment, cystic nature
Képénékian et al	20	44.68	–	15/17 (88.24%)	75.00%	Surgical w/chemical cure	Mean: 196 ± 100	Preoperative baseline prolactin levels, tumor size, previous treatment
Shimon et al	8	11.11	–	4/8 (50.00%)	50.00%	Surgical w/chemical cure	Mean: 93.6 ± 61.2	Giant prolactinoma (tumor size), cavernous sinus invasion, extrasellar involvement, surgical approach, preoperative prolactin levels
Vale et al	13	61.54	1/1 (100.00%)	9/12 (75.00%)	76.92%	Surgical w/chemical cure	Mean: 48	Tumor size, cavernous sinus invasion, postoperative prolactin levels, previous treatment
Vroonen et al	56	60.98	–	–	32.14%	Surgical w/chemical cure	88.5	Extrasellar involvement, previous treatment, postoperative prolactin level
Tamasauskas et al	32	100	19/32 (59.38%)	–	59.38%	Surgical w/chemical cure	Median: 88.5	Tumor size, previous treatment, preoperative prolactin levels, postoperative prolactin levels, postoperative treatment
Sinha et al	122	41.28	10/12 (83.33%)	40/83 (48.19%)	77.05%	Surgical w/chemical cure	Mean: 50.4 ± 32.4	Tumor size, surgical approach, preoperative prolactin levels, postoperative prolactin levels
Qu et al	87	0	13/18 (72.22%)	24/69 (34.78%)	72.41%	Surgical w/chemical cure	Median: 45.0	Extrasellar involvement, cavernous sinus invasion, previous treatment, preoperative prolactin level, postoperative prolactin level
Yu et al	18	13.33	–	4/18 (22.22%)	22.22%	Surgical w/chemical cure	Mean: 31.7	Giant prolactinoma (tumor size), cavernous sinus invasion, preoperative medical treatment, surgical approach, postoperative prolactin levels
Asano et al	8	0	–	8/8 (100.00%)	100%	Surgical w/chemical cure	Mean: 42.48 ± 14.52	Preoperative prolactin levels, postoperative prolactin levels
Gökalp et al	550	28.36	200/311 (64.31%)	15/222 (6.76%)	38.74%	Surgical cure	Mean: 86.4	Tumor size, extrasellar involvement, surgical approach, preoperative baseline prolactin levels
Jho et al	5	80.00	–	–	40.00%	Surgical w/chemical cure	Not reported	Postoperative prolactin levels, surgical approach
Merola et al	49	75.40	24/25 (96.00%)	23/24 (95.83%)	91.84%	Surgical w/chemical cure	60	Postoperative prolactin levels, preoperative medical treatment
Zada et al	20	Not reported	–	–	40.00%	Surgical cure	Median: 16	Extrasellar involvement, preoperative medical treatment
Gsponer et al	52	77.48	16/25 (64.00%)	10/26 (38.46%)	46.15%	Surgical w/chemical cure	Not reported	Surgical approach, cavernous sinus invasion, preoperative medical treatment, postoperative prolactin levels
Zielinski et al	48	92	–	–	71%	Surgical w/chemical cure	84	Cavernous sinus invasion (Knosp score), tumor size, plurihormonal vs pure lactotroph adenomas, postoperative prolactin levels
Losa et al	120	77.5	46/59 (78%)	31/61 (50.8%)	64.2%	Surgical cure	Mean: 50.2 ± 3.0	Age, sex, preoperative prolactin levels, tumor size, extrasellar involvement, dural infiltration
Micko et al	60	83	–	–	67%	Surgical cure	Mean: 37	Tumor enclosed by pituitary gland or not
Kreutzer et al	212	63	47/56 (84.8%)	–	42.7%	Surgical cure	Mean: 19.6	Preoperative prolactin levels, tumor size, extrasellar involvement
Present study	56	71.0	11/15 (73%)	14/39 (36%)	46%	Surgical cure	Median: 39.4	Cavernous sinus invasion, postoperative d 1 prolactin levels, tumor size, sex, prior transsphenoidal resection, extent of resection
Present study	56	71.0	13/15 (87%)	22/39 (56%)	64%	Surgical w/chemical cure	Median: 39.4	Preoperative prolactin levels, postoperative d 1 prolactin levels, tumor size, prior transsphenoidal surgery, extent of resection, cavernous sinus invasion