Management and outcome of metastatic pheochromocytomas/paragangliomas: an overview

Metastatic pheochromocytomas and paragangliomas (PPGLs) occur in about 5-26% of cases and are characterized by a heterogeneous prognosis. Metastases can be synchronous at the initial diagnosis, but they can occur also many years after surgery for the primary tumor. To date, the treatment of patients affected by metastatic PPGLs represents a clinical challenge because of the lack of guidelines.

The aim of this article is to review the available management options and their impact on the outcomes of patients with metastatic PPGLs.

Generally, treatments are not curative. Surgery, when possible, can be used to reduce hormonal symptoms and cardiovascular morbidity. Chemotherapy plays a role in patients with high burden tumor and rapid disease progression. Tyrosine kinases inhibitors (TKIs) might be considered for their ability to block the angiogenesis and cell growth. Radiation therapy and interventional radiology techniques can help in the management of local metastases to control symptoms and avoid tumor progression. On the other hand, peptide receptor radionuclide therapy (PRRT), using ⁹⁰Y or ¹⁷⁷Lu-DOTATATE, could be a promising therapy. In addition, high specific ¹³¹I-MIBG was approved by the Food and Drug Administration (FDA) in the US for the treatment of patients affected by metastatic and unresectable ¹³¹I-MIBG positive PPGLs. Considering the different pathways involved in the pathogenesis of PPGLs, several target therapies have been proposed and are under evaluation in clinical trials.

The choice of the appropriate treatment should be based on multidisciplinary and personalized approach taking into account the rarity and the variability of these tumors.