Effects of Peptide Receptor Radiotherapy in Patients with Advanced Paraganglioma and Pheochromocytoma: A Nation-Wide Cohort Study

Simple Summary Pheochromocytomas and paragangliomas are rare neuroendocrine tumours that originate from the adrenal medulla or extra-adrenal sympathetic or parasympathetic ganglia. They have the potential to secrete catecholamines, leading to e.g., hypertension. The only curative treatment modality is radical surgery. In disseminated diseases, limited data are available to guide proper medical treatment. Peptide receptor radionuclide therapy (PRRT) represents a rather novel treatment modality for these tumours. In the present nation-wide study, including all patients (n = 28) treated with PPRT in Denmark, we show a median overall survival of 72 and a median progression-free survival of 30 months with low toxicity. In conclusion, PRRT seems to represent an effective treatment option. The sequence of PRRT in treatment algorithms for pheochromocytomas and paragangliomas remains to be clarified.Abstract Introduction: Pheochromocytomas and paragangliomas are rare neuroendocrine tumours that originate from chromaffin cells within the adrenal medulla or extra-adrenal sympathetic ganglia. Management of disseminated or metastatic pheochromocytomas and paragangliomas continues to pose challenges and relies on limited evidence. Method: In this study, we report retrospective data on median overall survival (OS) and median progression-free survival (PFS) for all Danish patients treated with peptide receptor radionuclide therapy (PRRT) with 177Lu-Dotatate or 90Y-Dotatate over the past 15 years. One standard treatment of PRRT consisted of 4 consecutive cycles with 8-14-week intervals. Results: We included 28 patients; 10 were diagnosed with pheochromocytoma and 18 with paraganglioma. Median age at first PRRT was 47 (IQR 15-76) years. The median follow-up time was 31 (IQR 17-37) months. Eight patients died during follow-up. Median OS was 72 months, and 5-year survival was 65% with no difference between pheochromocytoma and paraganglioma. Patients with germline mutations had better survival than patients without mutations (p = 0.041). Median PFS after the first cycle of PRRT was 30 months. For patients who previously received systemic treatment, the median PFS was 19 months, compared with 32 months for patients with no previous systemic treatment (p = 0.083). Conclusions: The median OS of around 6 years and median PFS of around 2.5 years found in this study are comparable to those reported in previous studies employing PRRT. Based on historical data, the efficacy of PRRT may be superior to 131I-MIBG therapy, and targeted therapy with sunitinib and PRRT might therefore be considered as first-line treatment in this patient group.