Guideline sources The following summarized guidelines for the evaluation and management of pituitary carcinoma are prepared by our editorial team based on guidelines from the European Society of Endocrinology (ESE 2018), the Acromegaly Consensus Conference (ACC 2018), and the Endocrine Society (ES 2011). 1 2 3 Guidelines 1. Screening and diagnosis Diagnosis: suspect an aggressive pituitary tumor in patients with a radiologically invasive tumor and unusually rapid tumor growth rate, or clinically relevant tumor growth despite optimal standard therapies (surgery, radiotherapy, and conventional medical treatments). E 2. Diagnostic investigations Brain imaging: obtain imaging (MRI in most instances) for quantification of tumor dimensions, invasion, and growth. E https://web.pathway.md/diseases/reckyp8xNHmEgtzD9 1/4 6/29/23, 11:11 PM Pituitary carcinoma Pathway Imaging for staging: obtain evaluation for metastatic disease in patients with an aggressive pituitary tumor and either site-specific symptoms or discordant biochemical and radiological findings. E Laboratory testing: obtain full endocrine laboratory evaluation in patients with aggressive pituitary tumors. E Genetic testing: consider obtaining germline genetic testing in patients with aggressive pituitary tumors based on young age at presentation or family history of pituitary or endocrine neoplasia, as recommended for patients with nonaggressive pituitary tumors. C 3. Diagnostic procedures Histopathology: Obtain histopathological analysis, including a minimum immunodetection of pituitary hormones and Ki-67 proliferative index evaluation, in all patients with pituitary tumors. Obtain at least p53 immunodetection and mitotic count assessment when the Ki-67 index is 3%. B Interpret histopathological results in the clinical context of the individual patient. B 4. Medical management General principles: Discuss patients with aggressive pituitary tumors and carcinomas in a multidisciplinary expert team meeting (including endocrinologists, neurosurgeons, pituitary pathologists, neuroradiologists, radiation oncologists, and medical oncologists). E Offer standard medical treatment with maximally tolerated doses in order to control tumor growth, as per current guidelines. E Temozolomide: As per ACC 2018 guidelines, offer temozolomide in patients with unusually aggressive or proven malignant pituitary tumors. Ensure close cooperation with a neuro-oncologist for such treatment. B As per ESE 2018 guidelines: Offer temozolomide 150-200 mg/m for 5 consecutive days every 28 days B as first-line chemotherapy in patients with aggressive pituitary tumors and pituitary carcinomas following documented tumor growth. B Consider combining temozolomide with radiotherapy (Stupp protocol) in patients with rapid tumor growth if maximal doses of radiotherapy have not been reached. C As per ES 2011 guidelines, consider offering temozolomide in patients with malignant prolactinomas. C Other cytotoxic therapies: consider offering a trial of other systemic cytotoxic therapy in patients with rapid tumor progression on temozolomide treatment. Insufficient evidence to recommend a particular chemotherapeutic regimen. C https://web.pathway.md/diseases/reckyp8xNHmEgtzD9 2/4 6/29/23, 11:11 PM Pituitary carcinoma Pathway 5. Therapeutic procedures Radiotherapy: As per ESE 2018 guidelines, offer radiotherapy in patients with clinically relevant tumor growth despite surgery in nonfunctioning tumors or surgery and standard medical treatment in functioning tumors. B Show 2 more As per ES 2011 guidelines, consider offering radiation therapy in patients with aggressive or malignant prolactinomas. C Locoregional therapies: consider offering locoregional therapies in patients with isolated metastases, independent of decisions regarding the need for systemic treatment. C 6. Surgical interventions Indications for surgery: Perform surgery by a neurosurgeon with extensive experience in pituitary surgery. B Discuss repeat surgery with an expert neurosurgeon before considering other treatment options. B 7. Follow-up and surveillance Assessment of treatment response: obtain careful clinical observation for potential adverse effects and monitor hematological parameters and LFTs during treatment. B Show 3 more Serial imaging and laboratory assessment: obtain imaging (MRI in most instances) every 3- 12 months as guided by prior tumor growth rate and/or location of the tumor (proximity to vital structures). B Show 2 more Management of recurrence: consider offering a second trial of 3 cycles of temozolomide in patients developing a recurrence following response to temozolomide treatment. C Clinical findings Symptoms Past medical history Headache Acromegaly Bone metastasis Neurological exam Cushing's syndrome Hyperprolactinemia Cranial nerve palsy Liver metastasis Visual field defect Lung metastasis Imaging findings Lab findings Hydrocephalus https://web.pathway.md/diseases/reckyp8xNHmEgtzD9 3/4 6/29/23, 11:11 PM Pituitary carcinoma Pathway Pituitary mass ACTH serum GH l ti References 1. Gerald Raverot, Pia Burman, Ann McCormack et al. European Society of Endocrinology Clinical Practice Guidelines for the management of aggressive pituitary tumours and carcinomas. Eur J Endocrinol. 2018 Jan;178 1 G1 G24. Open 2. Melmed S, Casanueva FF, Hoffman AR et al. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011 Feb;96 2 273 88. Open 3. Melmed S, Bronstein MD, Chanson P et al. A Consensus Statement on acromegaly therapeutic outcomes. Nat Rev Endocrinol. 2018 Sep;14 9 552 561. Open 4. A Luger, L H A Broersen, N R Biermasz et al. ESE Clinical Practice Guideline on functioning and nonfunctioning pituitary adenomas in pregnancy. Eur J Endocrinol. 2021 Aug 23;185 3 G1 G33. Open https://web.pathway.md/diseases/reckyp8xNHmEgtzD9 4/4