Peptide Receptor Radionuclide Therapy as a Novel Treatment for Metastatic and Invasive Phaeochromocytoma and Paraganglioma

At present there is no clinical guideline or standardised protocol for the treatment of metastatic or invasive phaeochromocytoma and paraganglioma (collectively known as PPGL) due to the rarity of the disease and the lack of prospective studies or extended national databases. Prognosis is mainly determined by genetic predisposition, tumour burden, rate of disease progression, and location of metastases. For patients with progressive or symptomatic disease that is not amenable to surgery, there are various palliative treatment options available. These include localised therapies including radiotherapy, radiofrequency, or cryoablation, as well as liver-directed therapies for those patients with hepatic metastases (e.g., transarterial chemoembolisation) and systemic therapies including chemotherapy or molecular targeted therapies. There is currently intense research interest in the value of radionuclide therapy for neuroendocrine tumours, including phaeochromocytoma and paraganglioma, with either iodine-131 (131I)-radiolabelled metaiodobenzylguanidine or very recently peptide receptor radionuclide therapy (PRRT), and the most important contemporary clinical studies will be highlighted in this review. The studies to date suggest that PRRT may induce major clinical, biochemical, and radiological changes, with 177Lu-DOTATATE being most efficacious and presenting less toxicity than 90Y-DOTATATE. Newer combination therapies with combined radioisotopes, or combinations with chemotherapeutic agents, also look promising. Given the favourable efficacy, logistic, and safety profiles, we believe that PRRT will probably become the standard treatment for inoperable metastatic PPGL in the near future, but we await data from definitive randomised controlled trials to understand its role.