The incidence of metastatic pheochromocytoma ranges from 3% to 36% or even higher, depending on the genetic background and location of the primary tumor . Location of metastatic lesions appears to affect patient’s survival. Short-term survivors (less than 5 years) tend to be patients with metastatic lesions in liver and lungs, whereas long-term survivors are those with metastatic lesions in bones . The overall 5-year survival rate varies between 34% and 60%. This poor prognosis emphasizes the need to adequately identify either those patients with already existing metastatic disease or, preferably, those who may develop metastases. Currently, however, except for the presence of the SDHB mutation, large size or an extra-adrenal location of the primary tumor, there are no reliable markers for predicting a high likelihood of developing metastatic disease.

Although several therapeutic options exist for patients with metastatic pheochromocytoma, all are limited and there is no cure. Less than 40% of patients with metastatic pheochromocytoma respond (mostly partial remission) to currently used therapeutic modalities such as MIBG or chemotherapy. Tumor size reduction palliates symptoms, but a survival advantage of debulking is not proven. However, reduced tumor burden can facilitate subsequent radiotherapy or chemotherapy, but again this is not proven. External-beam irradiations of bone metastases, tumor embolization, or radiofrequency ablation provide some treatment alternatives. Chemotherapy with a combination of cyclophosphamide, vincristin and dacarbazine can provide tumor regression and symptom relief in up to 50% of patients, but the responses are usually short . To date, 131I-MIBG therapy is the single most valuable adjunct to surgical treatment of malignant pheochromocytomas. As a single agent 131I-MIBG has limited efficacy for cure, and there is no consensus on what doses to use for treating either bone or organ metastases . Although according to previously published articles chemo- or 131I-MIBG therapy should be initiated only in patients in whom the quality of life is affected or metastatic lesions are growing aggressively and affect local surrounding tissue, it is our personal opinion that all patients with metastatic pheochromocytoma should be evaluated and considered for immediate treatment.

Clinicians using the above therapies, particularly chemotherapy, should be aware of potentially fatal complications arising from excessive catecholamine release as tumor cells are destroyed (usually within the first 24 hr). With use of MIBG a major complication is bone marrow suppression usually 4 weeks after initiation of therapy. Octreotide therapy is also available for malignant pheochromocytoma, however, the experience with this therapy is very limited with reports showing different responses . Therefore, we recommend this treatment option to be used only in patients in whom chemo- or MIBG therapy cannot be carried out (e.g. negative MIBG scan or severe bone marrow suppression). Octreotide therapy requires positive Octreoscan.