Phe ochromocytomas and paragangliomas (PPGLs) are rare neural crest-derived tumors with malignant potential and a highly variable natural history, where some patients achieve a cure through surgical resection, while others experience an aggressive and protracted disease course characterized by recurrence and metastasis. While currently no definitive curative treatment exists for metastatic PPGLs, ongoing trials and advances in biology of the disease present a beacon of hope. We present a case that illustrates a 15-year treatment journey, illustrating the complexity of metastatic PPGL treatment with different modalities, each with distinct efficacy and toxicity profiles. The choice of treatment is often an art, as much as it is based on evidence, as the clinician must balance among several factors, including tumor-related (pace of progression, tumor burden) and patient-related (functional status, symptoms, general health) ones. Through a stepwise approach, this discussion aims to provide insights into the evolving landscape of metastatic PPGL management.

Center for Adrenal Endocrine Tumors AKESO Prague 5 155 00 Czech Republic

Department of Endocrinology Royal North Shore Hospital and Cancer Genetics Laboratory Kolling Institute University of Sydney Sydney New South Wales 2064 Australia

Department of Medicine 4 University Hospital Ludwig Maximilians University Munich 80336 Munich Germany

Department of Nuclear Medicine Aix Marseille University La Timone University Hospital 13005 Marseille France

Developmental Therapeutics Branch Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD 20892 USA

Molecular Imaging Branch National Cancer Institute National Institutes of Health Bethesda MD 20892 USA

National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Bethesda MD 20892 USA

National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development Bethesda MD 20892 USA

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J Clin Endocrinol Metab. 2025 Sep 16;110(10):e3550. doi: 10.1210/clinem/dgaf442. PubMed

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