====== 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 ((Chanson P, Wolf P. Clinically Non-Functioning Pituitary Neuroendocrine Tumors. Presse Med. 2021 Dec;50(4):104086. doi: 10.1016/j.lpm.2021.104086. Epub 2021 Oct 28. PMID: 34718111.)). see also [[Recurrent Clinically Non-Functioning Pituitary Neuroendocrine Tumor treatment]]. ===== Clinically Non-Functioning Pituitary Neuroendocrine Tumor surgery ===== see [[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% ((Lucas JW, Bodach ME, Tumialan LM, et al. Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Primary Management of Patients With Nonfunctioning pituitary neuroendocrine tumors. Neurosurgery. 2016; 79:E533–E535)). These agents are therefore not recommended as a primary treatment due to lack of a significant and consistent response ((Lucas JW, Bodach ME, Tumialan LM, et al. Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Primary Management of Patients With Nonfunctioning pituitary neuroendocrine tumors. Neurosurgery. 2016; 79:E533–E535)). ● 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 ((Dekkers OM, Hammer S, de Keizer RJ, et al. The natural course of non-functioning pituitary macroadenomas. Eur J Endocrinol. 2007; 156:217–224)) ((Arita K, Tominaga A, Sugiyama K, et al. Natural course of incidentally found nonfunctioning pituitary neuroendocrine tumor, with special reference to pituitary apoplexy during follow-up examination. J Neurosurg. 2006; 104:884–891)) Observation only is not recommended for symptomatic NFPAs ((Lucas JW, Bodach ME, Tumialan LM, et al. Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Primary Management of Patients With Nonfunctioning pituitary neuroendocrine tumors. Neurosurgery. 2016; 79:E533–E535)). ===== 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 defect]]s). ==== Radiologic follow-up ==== Level III ((Ziu M, Dunn IF, Hess C, et al. Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Posttreatment Follow- up Evaluation of Patients With Nonfunctioning pituitary neuroendocrine tumors. Neurosurgery. 2016; 79:E541– E543)) 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 ==== ((Ziu M, Dunn IF, Hess C, et al. Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Posttreatment Follow- up Evaluation of Patients With Nonfunctioning pituitary neuroendocrine tumors. Neurosurgery. 2016; 79:E541– E543)) 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 ((Ziu M, Dunn IF, Hess C, et al. Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Posttreatment Follow- up Evaluation of Patients With Nonfunctioning pituitary neuroendocrine tumors. Neurosurgery. 2016; 79:E541– E543)) 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 ((Dekkers OM, Pereira AM, Romijn JA. Treatment and Follow-Up of Clinically Nonfunctioning. Pituitary Macroadenomas. J Clin Endocrinol Metab. 2008;93:3717–26)) 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 ((Dekkers OM, Hammer S, de Keizer RJ, Roelfsema F, Schutte PJ, Smit JW, Romijn JA, Pereira AM. The natural course of non-functioning pituitary macroadenomas. Eur J Endocrinol. 2007 Feb;156(2):217-24. PubMed PMID: 17287411. )). 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 ((Karavitaki N, Collison K, Halliday J, et al. What is the natural history of nonoperated nonfunctioning pituitary neuroendocrine tumors. Clin Endocrinol (Oxf) 2007;67:938–43.)) Treatment options for [[nonfunctioning pituitary neuroendocrine tumor]]s (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 ((Esposito D, Olsson DS, Ragnarsson O, Buchfelder M, Skoglund T, Johannsson G. Non-Functioning Pituitary Neuroendocrine Tumors: indications for pituitary surgery and post-surgical management. Pituitary. 2019 Apr 22. doi: 10.1007/s11102-019-00960-0. [Epub ahead of print] Review. PubMed PMID: 31011999. )). ---- 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 [[macroadenoma]]s. Therapy is directed at eliminating mass effect and correcting [[hypopituitarism]]. There are anecdotal reports of tumor shrinkage during therapy with either [[dopamine agonist]]s or [[somatostatin agonist]]s; 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 ((Mayson SE, Snyder PJ. Silent (clinically nonfunctioning) pituitary neuroendocrine tumors. J Neurooncol. 2014 May;117(3):429-36. doi: 10.1007/s11060-014-1425-2. Epub 2014 Mar 28. PubMed PMID: 24676675.)). ===== Radiosurgery ===== [[Clinically Non-Functioning Pituitary Neuroendocrine Tumor radiosurgery]] ===== References =====