Metastatic pheochromocytoma and paraganglioma: Management of endocrine manifestations, surgery and ablative procedures, and systemic therapies

Metastatic pheochromocytomas and paragangliomas (MPPGs) are rare neuroendocrine tumors. Most patients present with advanced disease that is associated with manifestations of catecholamine release. Surgical resection of the primary tumor and ablative therapies of metastases—whenever possible—may improve clinical outcomes and, perhaps, lengthen the patient's overall survival. Significant steps in understanding the genetic alterations linked to MPPGs and scientific progress made on cancers that share a similar pathogenesis are leading to the recognition of potential systemic therapeutic options. Data derived from clinical trials evaluating targeted therapies such as tyrosine kinase inhibitors, radiopharmaceuticals, immunotherapy, and combinations of these will likely improve the outcomes of patients with advanced and progressive MPPGs. Exemplary of this success is the recent approval in the United States of the high-specific-activity iodine¹³¹ meta-iodine-benzylguanidine (MIBG) for patients with unresectable and progressive MPPGs that express the noradrenaline transporter. This review will discuss the therapeutic approaches for patients with MPPGs.