Prognostic Factors of Malignant Pheochromocytoma and Paraganglioma: A Combined SEER and TCGA Databases Review

Abstract

Pheochromocytoma (PCC) and paraganglioma (PGL) are rare malignancies while pathogenesis is strongly influenced by genetics. The prognostic factors of these patients remain poorly defined. We aim to study the epidemiology and survival pattern by analyzing the combination of SEER and Cancer Genome Atlas (TCGA) database. Primary outcome was overall survival (OS) and disease specific survival (DSS). Between 1973 and 2013, a total of 1014 patients with PGL or PCC were analyzed. Younger age and female were associated with better outcomes. The incidence of second primary malignancy in PGL/PCC patients was about 14.6%. This population had a significant longer DSS. Other factors, including surgical resection and origin from of aortic/carotid bodies, conferred remarkable survival advantage. In contrast, distant spread portended worse prognosis. Laterality, race, positive serum catecholamine marker did not demonstrate a significant association with OS and DSS. By analyzing TCGA database with total 184 patients were identified. Eighty out of 184 patients (43.5%) had at least one pathogenic mutation. Female had higher ratio of pathogenic mutations than male (58.7% vs. 41.3%) and NF1 mutation was associated with elderly population. SHDB mutation had higher percentage in male. Twenty-nine patients (15.8%) had 2 or more primary. ATRX was the most common oncogenic mutations in metastatic cohort. In conclusion, younger age, female sex, origin from aortic/carotid bodies, complete surgical resection, regional disease, as well as concomitant second primary malignancies were associated with better prognosis. The prognostic value of radiotherapy and oncogenomics warrants further investigation.

Prognostic Nomograms for Predicting Overall Survival and Cancer‐Specific Survival of Patients With Malignant Pheochromocytoma and Paraganglioma

“…In our study, we evaluated the effect of surgery (including radical and partial resection) on OS and CSS in patients with PPGL. This is consistent with the previous studies ( 14 ). However, the corresponding effect requires combination with other treatments ( 25 ).…”

“…Currently, there is inconsistent data on the role of gender in PPGL outcomes. Some studies have shown that gender is an independent risk factor ( 14 ), while others have shown that gender does not play a significant role in the disease outcome ( 15 ). In our study, the female patients indicated better OS, which was consistent with the previous reports ( 16 , 17 ).…”

Molecular imaging and radionuclide therapy of pheochromocytoma and paraganglioma in the era of genomic characterization of disease subgroups

“…The more intensive follow-up imaging is required in metastatic patients or patients who are at high risk to develop metastases. Such high risk-factors have been identified as SDHB, SDHA germline mutations, ATRX mutation, male sex, patient with large primary tumors (various studies have identified that from >4.5-5 cm to >10 cm), noradrenergic or dopaminergic biochemical phenotype, older age at primary tumor diagnosis (>40-50 years), and high proliferative index (Ayala-Ramirez et al 2011, King et al 2011, Schovanek et al 2014, Plouin et al 2016, Hamidi et al 2017, Jha et al 2019a, Hescot et al 2019, Mei et al 2019. These patients should be followed up indefinitely involving either whole-body CT/MRI and/or functional imaging.…”

Collet-Sicard Syndrome as the Presentation of Malignant Pheochromocytoma

“…Given that ∼95% of malignant pheo’s are intra-abdominal in origin, elevated catecholamines should further compel abdominal imaging for both prognostication and treatment guidance. 10…”