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The most common sites of metastasis for pheochromocytoma or extra-adrenal paraganglioma are lymph nodes, bones, lungs, and liver. Patients with known or suspected malignancy should undergo staging with computed tomography or magnetic resonance imaging as well as functional imaging (e.g., with 123 I-metaiodobenzylguanidine [MIBG]) to determine the extent and location of disease. Patients are often very symptomatic from excess catecholamine secretion. Phenoxybenzamine is effective, and metyrosine, which is a drug that blocks catecholamine synthesis, can be added if needed.
If all identifiable disease is resectable, including a limited number of distant metastases, surgery can provide durable palliation of symptoms and occasional long-term remission. If disease is unresectable, surgical debulking will not improve survival; however, it is occasionally indicated for symptom palliation.
Chemotherapy has not been shown to improve survival in patients with metastatic pheochromocytoma; however, chemotherapy can be attempted for the palliation of symptoms. The best-established chemotherapy regimen is a combination of cyclophosphamide, vincristine, and dacarbazine (the Averbuch protocol). Results of this regimen in 18 patients after 22 years of follow-up demonstrated a complete response rate of 11%, a partial response rate of 44%, a biochemical response rate of 72%, and a median survival of 3.3 years.[Level of evidence: 3iiiDiv] Several other chemotherapy regimens have been used in small numbers of patients, but the overall results were disappointing.[3,4]
Novel targeted therapies are emerging as potential treatment strategies for metastatic pheochromocytoma. Disappointing initial results were reported with the mammalian target of rapamycin (mTOR) inhibitor everolimus, but results from a very small number of patients treated with the tyrosine kinase inhibitor sunitinib have been more promising.[6,7]
131 I-MIBG radiation therapy has been used for the treatment of MIBG-avid metastases.[8,9] In a phase II study of high-dose 131 I-MIBG radiation therapy involving 49 patients, 8% had a complete response, 14% had a partial response, and the estimated 5-year survival was 64%.[Level of evidence: 3iiiDiv] Approximately 60% of metastatic pheochromocytoma or paraganglioma sites are MIBG-avid; protocol-based treatment with other experimental radiolabeled agents, such as radiolabeled somatostatin, can be considered for metastases that do not take up MIBG.
Other palliative treatment modalities include external-beam radiation therapy (e.g., for palliation of bone metastases) and embolization, radiofrequency ablation, or cryoablation (e.g., for palliation of bulky hepatic metastases or isolated bony metastases).