Positive Impact of Genetic Test on the Management and Outcome of Patients With Paraganglioma and/or Pheochromocytoma

Abstract

Context Pheochromocytomas and paragangliomas (PPGLs) are characterized by a strong genetic component, with up to 40% of patients carrying a germline mutation in a PPGL susceptibility gene. International guidelines recommend that genetic screening be proposed to all patients with PPGL. Objective Our objective was to evaluate how a positive genetic test impacts the management and outcome of patients with SDHx or VHL-related PPGL. Design We performed a multicentric retrospective study involving 221 propositi carrying an SDHB, SDHD, SDHC, or VHL germline mutation. 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 Genetic patients had better follow-up than historic patients, with a greater number of examinations and a reduced number of patients lost to follow-up (9.6% vs 72%, respectively). During follow-up, smaller (18.7 vs 27.6 mm; P = 0.0128) new PPGLs and metastases as well as lower metastatic spread were observed in genetic patients. Of note, these differences were reversed in the historic cohort after genetic testing. Genetic patients who developed metachronous metastases had a better 5-year survival rate than historic patients (P = 0.0127). Conclusion Altogether, our data suggest that early knowledge of genetic status had a positive impact on the management and clinical outcome of patients with a germline SDHx or VHL mutation.

Clinical implications of the oncometabolite succinate in SDHx‐mutation carriers

“…Screenings advices do not only differ between the different mutations, but also over time, because studies on penetrance differ over time regarding the population studied (index included or not), the imaging methods used and the duration of follow‐up. Adherence to screening, leads to the detection of smaller PCC/PGL and might even lead to an improved survival for patients who develop metastases, although this is based on only few patients …”

A case of an unexpected posterior mediastinal functional paraganglioma: case report and literature review

“…In addition, PGL/PCC have the highest rate of germline susceptibility, which is at almost 40% [10][11][12]. Thus genetic testing, combined with clinical manifestations, biochemical, and imaging assessments, can help to understand tumor secretion, tumor malignancy, and develop treatment and follow-up plans for PPGL [12,13]. For this missed diagnosis, tests for hormones and their metabolites or genetics were not performed.…”

Precision Surgery for Pheochromocytomas and Paragangliomas

“…Positive benefits of early genotyping in a P-PGL cohort was demonstrated by a French study. A set of 221 patients with P-PGL with SDHB, SDHC, SDHD, or VHL germline mutations revealed that patients who knew their genetic mutation within one year of initial P-PGL diagnosis compared to patients knowing their genetic mutation more than a year after initial diagnosis had improved follow-up (more frequent examinations, less patients lost to follow-up), smaller size of subsequent new P-PGLs discovered, lower metastatic spread, and improved 5 year survival rate in the patients who developed metachronous metastases [43]. Germline and somatic mutations in more than 20 genes (EPAS1,…”