Clinically Non-Functioning Pituitary Neuroendocrine Tumor Treatment
In the absence of an established medical therapy, surgery is the mainstay of treatment, unless contraindicated or in particular situations (e.g. small incidentalomas, distance from optic pathways). Resection, generally via a trans-sphenoidal approach (with the help of an endoscope), should be performed by a neurosurgeon with extensive experience in pituitary surgery, in order to maximize the chances of complete resection and minimize complications. If a tumor remnant persists, watchful waiting is preferred to routine radiotherapy, as long as the tumor residue does not grow and is distant from the optic pathways. NFPA can sometimes recur even after complete resection, but predicting the individual risk of tumor remnant progression is difficult. Postoperative irradiation is only considered in case of residual tumor growth or relapse, due to its potential side effects 1).
see also Recurrent Clinically Non-Functioning Pituitary Neuroendocrine Tumor treatment.
Clinically Non-Functioning Pituitary Neuroendocrine Tumor surgery
Literature on nonsurgical treatment modalities for NFPAs
● Medical management: reported tumor response rates using dopamine agonists (e.g. Bromocriptine) in 0–60% of cases, somatostatin analogs (e.g. Octreotide) in 12–40%, and combination therapy in 60% 2). These agents are therefore not recommended as a primary treatment due to lack of a significant and consistent response 3).
● XRT: studies have not shown equivalence or superiority of XRT as primary management compared to surgical management. XRT has been demonstrated to be an effective adjunctive therapy for post-op residual tumor or recurrence
● Natural history: reports of management with observation only are rare. Two studies showed tumor progression in 40–50%, and 21–28% required surgery 4) 5)
Observation only is not recommended for symptomatic NFPAs 6).
Follow-up recommendations for nonsurgically managed NFPAs
For asymptomatic microadenomas (< 1 cm dia), recommend: F/U pituitary MRI at years 1, 2, 5 and ± 10 (can stop F/U after 10 and possibly 5 years if no growth). For tumors > 1 cm, recommend: check visual fields, pituitary bloodwork (to R/O pituitary insuffi- ciency) and pituitary MRI at years 0.5, 1, 2 & 5, and any time symptoms develop.
Gonadotropin-secreting tumors
Rarely, a non-functional tumor may secrete gonadotropins (FSH, LH). This does not produce a clinical syndrome. Normal and neoplastic pituitary gonadotrophs have gonadotropin-releasing hormone (GnRH) receptors and may respond to long-acting GnRH agonists (by down-regulating receptors) or GnRH antagonists, but significant reductions in tumor size do not occur.
Posttreatment follow-up evaluation for nonfunctioning pituitary neuroendocrine tumors
Post treatment follow-up
Due to the lack of active hormonal products that can be followed with serial lab tests, follow-up relies primarily on serial imaging and monitoring for signs of mass effect from growing tumors (e.g. increasing visual field defects).
Radiologic follow-up
Level III 7)
1. T1WI fat sat & T2 weighted image MRI should be included in imaging of NFPAs after surgery or XRT
2. long-term surveillance for tumor regrowth or recurrence is recommended
3. patients with radiologically-proven gross total resection of NFPA require less frequent monitoring than those with subtotal resection
4. the first post-op imaging should be obtained 3–4 months post-op
Level inconclusive recommendations
1. there is insufficient evidence to make recommendations for frequency of imaging or length of surveillance after surgery or XRT for NFPAs
2. there is insufficient evidence to make recommendations for the timing of the first post-XRT imaging
Endocrinologic follow-up
Level III 9)
1. evaluation for endocrinologic pituitary dysfunction is recommended after surgery and/or XRT for NFPAs
2. post-op adrenal function evaluation is recommended on post-op day 2, week 6, and 12 months
Transsphenoidal surgery is the treatment of choice in NFMA patients with visual field defects.
The aim of treatment in these patients is to control tumor and also to improve and protect its visual function. However in many patients, pituitary dysfunction recovery cannot happen, thus, the transsphenoidal surgery is considered for restoration of visual function, rather than pituitary function 10)
However, most endocrinologists and neurosurgeons probably agree that local tumor control is also an indication for surgery. Macroadenomas elevating the chiasm would be considered an indication for surgery in many centers, even if there are no visual field defects 11).
The 'watch and wait' policy seems reasonable for microadenomas but is probably not a safe approach for macroadenomas, which appear to have a significant growth potential; in these cases, given the lack of established medical treatment, the decision for surgical intervention should balance the presence of significant comorbidities and the anaesthetic/peri-operative risks at presentation against the probability of tumour enlargement and its consequences, as well as the possible loss of advantages associated with early operation 12)
Treatment options for nonfunctioning pituitary neuroendocrine tumors (NFPAs) include active surveillance, surgical resection, and radiotherapy. Pituitary surgery is currently recommended as first-line treatment in patients with visual impairment due to adenomas compressing the optic nerves or chiasma. Radiotherapy is reserved for large tumor remnants or tumor recurrence following one or more surgical attempts. There is no consensus of optimal pre-, peri-, and postoperative management such as timing, frequency, and duration of endocrine, radiologic, and ophthalmologic assessments as well as management of smaller tumor remnants or tumor recurrence.
In clinical practice, there is a great variation in the treatment and follow-up of patients with NFPAs. We have, based on available data, suggested an optimal management strategy for patients with NFPAs in relation to pituitary surgery. Prospective trials oriented at drawing up strategies for the management of NFPAs are needed 13).
The management of Clinically Non-Functioning Pituitary Neuroendocrine Tumor invading the cavernous sinus (CS) is currently a balancing act between the surgical decompression of neural structures, radiotherapy and a wait-and-see policy.
Those tumors that require treatment are generally macroadenomas.
Therapy is directed at eliminating mass effect and correcting hypopituitarism. There are anecdotal reports of tumor shrinkage during therapy with either dopamine agonists or somatostatin agonists; however tumor response to medical treatment is not reliable.
see Cabergoline for Clinically nonfunctioning pituitary neuroendocrine tumor.
Silent adenomas that cause neurologic deficits require transsphenoidal surgery, but those that do not can be followed by MRI. Residual or recurrent disease is treated by radiation therapy, which is usually effective in preventing further growth but results in hormonal deficiencies in about half of patients. Dopamine agonists and somatostatin analogs are usually ineffective, but occasionally have been associated with reduced adenoma size 14).