This multicenter retrospective Italian study evaluates the efficacy and safety of PRRT in patients with advanced, unresectable or metastatic pheochromocytomas and paragangliomas (PPGL). Data from ~210 patients treated between 2000 and 2024 will be analyzed. The primary endpoint is disease control rate (DCR). Secondary endpoints include progression-free survival (PFS), overall survival (OS), and prognostic factors.

Pheochromocytomas (PHEO) and paragangliomas (PGL), collectively referred to as PPGL, are rare neuroendocrine tumors, sometimes secreting catecholamines, with variable clinical presentations and a risk of advanced/metastatic disease. In patients not eligible for curative treatment or with progressive disease, multimodal strategies may be used, including systemic and radiometabolic therapies, although shared therapeutic algorithms are difficult to define. In particular, in PPGL with somatostatin receptor expression documented by functional imaging, PRRT (Peptide Receptor Radionuclide Therapy) represents a therapeutic option used in an experimental/off-label setting, within authorized clinical protocols or clinical trials, as reported in the literature. Between 2000 and 2024, several centers in Italy treated PPGL patients with PRRT using different regimens (radionuclide, number of cycles, and timing), depending on experimental protocols, technological availability, and clinical characteristics. This heterogeneity, combined with the rarity of the disease, highlights the relevance of a structured national collection of real-world data to describe the efficacy and safety of PRRT in this setting. This is a retrospective, multicenter, non-profit observational pharmacological study including adult patients (≥18 years) with documented PPGL and advanced/unresectable or metastatic disease who received at least one cycle of PRRT within the study period. Patients must have available essential data to document treatment exposure and outcomes, including at least one post-treatment evaluation for disease control and minimum data for progression-free survival assessment.

PRRT exposure includes treatments administered within completed clinical trials or authorized protocols at participating centers. Data collected will include type of radionuclide(s), number of planned and administered cycles, treatment intervals, and reasons for treatment modifications or discontinuation, where available.

Inclusion Criteria:

• Documented diagnosis of pheochromocytoma or paraganglioma (PPGL) (sporadic or hereditary forms) with unresectable or metastatic disease.
• Treatment with peptide receptor radionuclide therapy (PRRT) administered with ⁷⁷Lu and/or ⁹⁰Y (including combination regimens), with t0 (first PRRT administration) between January 1, 2000 and February 28, 2024.
• Availability of essential data required by the protocol to document exposure (PRRT) and outcomes, including: PRRT start date (t0) and treatment details (radioisotope(s), number of cycles and/or cycles actually administered, intervals when available), At least one post-treatment evaluation suitable for determining disease control rate (DCR) (morphological imaging by CT/MRI ± functional imaging by PET/CT, and available clinical data), Follow-up information suitable for determining progression-free survival (PFS) within the predefined time window.
• Availability of follow-up up to 12 months from end of treatment (EoT), or documentation of progression and/or death occurring within 12 months.
• Required data and source documents are available at the enrolling center or obtainable from other Italian centers (e.g., PRRT-administering center or centers performing imaging/evaluations) through formal data transfer agreements (e.g., DTA) in compliance with applicable regulations.
• Privacy/consent requirements (general framework):

For living and contactable patients, consent for personal data processing will be managed according to the requirements/assessment of the Ethics Committee.

For deceased or non-contactable patients after reasonable documented efforts, inclusion may occur without consent, as it falls under situations of "impossibility to inform the subjects," in accordance with applicable regulations (Article 110 of the Italian Privacy Code and subsequent amendments), subject to Ethics Committee evaluation/opinion and implementation of appropriate safeguards.

Exclusion Criteria:

• Patients who did not receive at least one cycle of peptide receptor radionuclide therapy (PRRT).

Patients with sporadic or hereditary paraganglioma and pheochromocytoma (PPGL) with unresectable or metastatic disease, treated with peptide receptor radionuclide therapy (PRRT).