Metastatic
pheochromocytomas and
paragangliomas are rare and challenging
tumors. The
tumor burden, combined with excessive
catecholamine production, predispose to a broad spectrum of complications that range from
spinal cord compression to any organ damage, all of which may lead to decreased quality of life and overall survival. Current
therapies include surgery, systemic
chemotherapy and
radiopharmaceutical agents. Surgery is often a preferred
therapy because it may cure or allow a long-term remission in patients with locoregional or isolated resectable distant
metastases. Additionally, surgery can palliate symptoms related to
tumor burden or
catecholamine excess. However, in patients for whom surgery is not an option, systemic
chemotherapy and
radiopharmaceutical agents are preferred options. Systemic
chemotherapy and
radiopharmaceutical agents such as 131I-Metaiodobenzylguanidine (131I-MIBG) may cause partial responses or stabilization of disease with better blood pressure control and symptomatic and performance status improvement. However, as these
therapies are only palliative, patients' quality of life and personal preferences should always be considered. The recognition of molecular pathways involved in the
pheochromocytoma and
paraganglioma tumorigenesis has driven the development of new therapeutic options. Agents such as
tyrosine kinase, MAPK, PI3K, or
hypoxia inducible factor inhibitors, alone or in combination, may represent novel therapeutic strategies that could be evaluated in prospective clinical trials. Transcriptional profiling and the development of personalized
cancer medicine will help to pave the way for more specific therapeutic approaches and combinations.