Context: Paragangliomas and pheochromocytomas (PPGL) are rare neuroendocrine tumors, characterized by a strong genetic component. Indeed, up to 40% of patients carry a germline mutation in a PPGL susceptibility gene. In accordance with the international recommendations, genotyping of PPGL susceptibility genes is therefore proposed to all patients with PPGL, but it has actually never been shown whether the identification of a germline mutation in one PPGL susceptibility gene changes the outcome of mutation-carriers.
Objective: Our objective was to evaluate how a positive genetic test impacts the management and outcome of propositus patients with PPGL carrying a germline mutation in one of the four major PPGL susceptibility genes (SDHB, SDHD, SDHC and VHL).
Design: We performed a multicentric retrospective study on 221 propositus carrying a SDHB, SDHD, SDHC or VHL germline mutation and followed in 24 French clinical centers of the Group of Endocrine Tumors and/or the COMETE network. Patients were divided into two groups: Genetic patients, who were informed of their genetic status within the year following the first PPGL diagnosis, and Historic patients who only benefited from the genetic test several years after initial PPGL diagnosis.
Results: Compared to Historic patients, Genetic patients had a better follow-up, with a higher number of examinations and a reduced number of patients lost to follow-up (9.6% versus 72%). During follow-up, smaller (18.7 mm versus 27.6, P=0.0128) new PPGL and metastases as well as lower metastatic spread were observed in Genetic patients. Importantly, these differences were reversed in the Historic cohort after genetic testing. Genetic patients who developed metachronous metastases had a better 5-year survival than Historic ones (P=0.0127).
Conclusion: Altogether our study clearly shows the positive impact of the identification of an SDHx or VHL mutation in the management, clinical outcome and survival of patients with PPGL. It reveals, for the first time, the clinical benefits of the practice of oncogenetics for patients with a rare cancer and strongly strengthens the recommendations of the Endocrine Society to consider PPGL genetic testing in all patients affected by PPGL.
18 - 21 May 2019
European Society of Endocrinology