Diagnosis and treatment of Paragangliomas and Pheochromocytomas: A survey from the Italian Association for Neuroendocrine Tumors (ITANET)

Erica Pietroluongo¹Antonella Lucia Marretta²Mauro Cives^3*Elisa Andrini⁴Leonardo Della Sala⁵Elisabetta Dell'Unto⁶Alice Carli⁷Nevena Mikovic⁸Ilaria Mascagni⁹Francesco Panzuto¹⁰Salvatore Tafuto¹¹

• ¹Department of Clinical Medicine and Surgery, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy
• ²Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori IRCCS Fondazione Giovanni Pascale 80131, Naples, Italy., Naples, Italy
• ³Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, Bari, Italy., Bari, Italy
• ⁴Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum - Università di Bologna, Bologna, Italy, Bologna, Italy
• ⁵Endocrinology Unit, Department of Internal Medicine and Medical Specialties, School of Medical and Pharmaceutical Sciences, University of Genova, Genova, Italy., Genova, Italy
• ⁶Department of Medical-Surgical Sciences and Translational Medicine, Digestive Disease Unit, Sant'Andrea University Hospital, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy, Rome, Italy
• ⁷Radiology Unit, diagnostic and public health department, University of Verona, Policlinico GB Rossi, Verona, Italy., Verona, Italy
• ⁸Endocrinology Unit, Department of Clinical and Molecular Medicine, European Neuroendocrine Tumor Society (ENETS) Center of Excellence, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy, Rome, Italy
• ⁹Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy., Milano, Italy
• ¹⁰Department of Medical-Surgical Sciences and Translational Medicine, Digestive Disease Unit, Sant'Andrea University Hospital, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy., Rome, Italy
• ¹¹Department of Sarcoma and Rare Tumors, Istituto Nazionale Tumori I.R.C.C.S. ENETS Center of Excellence Fondazione "G.Pascale", 80131 Naples, Italy., Naples, Italy

Background: Pheochromocytomas (PCCs) and paragangliomas (PPGLs) are rare neuroendocrine neoplasms (NENs) with heterogeneous clinical presentations. Given the rarity of PCCs/PPGLs and the paucity of high-level evidence, therapeutic decisions and treatment sequences vary across institutions. This survey explored current diagnostic practices and treatment patterns among Italian healthcare professionals (HCPs) dedicated to NENs. Methods: An online survey was conducted among Italian HCPs, members of the Italian Association for Neuroendocrine Tumors (ITANET). The survey included 33 questions covering diagnosis, genetic counseling, imaging, and treatment approaches. Responses were collected from December 15, 2023, to May 30, 2024, and analyzed using descriptive statistics to identify trends in clinical practice. Results: We recorded 80/355 responses from invited HCPs (response rate: 23%). Most HCPs (90%) referred all PCC/PPGL patients for genetic counseling, with 71% adopting gene panels for syndromes like VHL, MEN2, and familial PPGLs. Functional imaging preferences included 68Ga-DOTA-peptide PET/CT (38%), 18F-DOPA PET/CT (26%), and 123I-MIBG scintigraphy (19%). First-line systemic treatments favored somatostatin analogs (39%), clinical trial enrollment (19%), and CVD chemotherapy (15%). Radioligand therapy (RLT) emerged as the preferred second-line treatment (49%). Overall, RLT was perceived as the most effective treatment for achieving objective responses, durable responses, and improving health-related quality of life. Conclusions: Clinical wisdom rather than formal evidence and guidelines recommendations appears to guide the management of PCC/PPGLs among Italian HCPs. International, multi-institutional clinical trials designed to take into account the rarity of PCCs/PPGLs are needed to generate high-level evidence and provide guidance for standard clinical practice.