European Standard Clinical Practice (ESCP) for Pediatric Pheochromocytoma and Paraganglioma: A Consensus-Based Approach

Background and Aims: Pediatric pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors characterized by excessive catecholamine secretion and a strong hereditary component, with germline mutations present in up to 80% of cases. Due to the rarity of pediatric PPGLs, evidence-based treatment guidelines are scarce. This European Standard Clinical Practice (ESCP) from the EXPeRT group in collaboration with the European Reference Network for Pediatric Oncology (ERN PaedCan) aims to provide harmonized recommendations for the diagnosis, treatment, and long-term management of pediatric PPGLs. Methods:Amultidisciplinary panel of experts in pediatric oncology, endocrinology, surgery, nuclear medicine, and pathology conducted a systematic review of the literature and existing clinical guidelines. A consensus-based approach was applied to formulate recommendations based on available evidence and expert opinion, following a standardized methodology adapted to rare tumors. The ESCP incorporates molecular diagnostics, biochemical and imaging assessments, surgical management, systemic therapy options, and long-term surveillance strategies. Results: At all stages of patient care, multidisciplinary team discussions is needed. The ESCP highlights key aspects of pediatric PPGL management, including the importance of initial diagnosis, systematic genetic testing, preoperative alpha-adrenergic blockade to prevent perioperative complications, even before any biopsy, and the role of functional imaging in tumor localization and staging. Wide en-bloc tumor resection remains the primary and peptide receptor radionuclide therapy are considered for metastatic or unresectable progressive disease. Focal therapies for oligometastatic lesions are discussed. Given the high recurrence risk, particularly in hereditary cases, lifelong surveillance with biochemical and imaging assessments is recommended. Conclusions: Implementation of these recommendations aims to optimize early diagnosis, harmonize therapy, improve treatment outcomes, and enhance long-term follow-up strategies for affected patients. Given the rapidly evolving therapeutic landscape, the ESCP will be updated as new clinical data emerge.