TNM Staging and Overall Survival in Patients with Pheochromocytoma and Sympathetic Paraganglioma

J Clin Endocrinol Metab. 2022 Nov 26;dgac677. doi: 10.1210/clinem/dgac677. Online ahead of print.


Background: Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors. Metastases develop in 15-20%. The American Joint Committee on Cancer (AJCC) established inaugural guidelines for PPGL tumor-node-metastasis (TNM) staging. The objective of this analysis is to investigate the associations between TNM staging and overall survival (OS).

Methods: We retrospectively applied the TNM staging at the time of diagnosis of the primary tumor. The primary outcome was OS. Unadjusted survival rates were estimated by the Kaplan-Meier method. Cox proportional hazards regression models were used to evaluate the associations between OS and covariates of interest.

Results: The study included 458 patients. Median OS was 18.0 (95% CI: 15.6-not reached) years. At diagnosis, 126 (27.5%) tumors were stage I, 213 (46.5%) were stage II, 47 (10.3%) were stage III, and 72 (15.7%) were stage IV. The 10-year OS probabilities were 0.844 (95% CI: 0.768-0.928) for patients with stage I tumors, 0.792 (95% CI: 0.726-0.865) for stage II, 0.595 (95% CI: 0.435-0.813) for stage III, and 0.221 (95% CI: 0.127-0.384) for stage IV. Compared with stage I, the hazard ratios (HR) for death were 1.50 (0.87-2.57) for stage II, 2.85 (1.45-5.63) for stage III, and 8.88 (5.16-15.29) for stage IV (p < 0.001). Compared with patients with no germline mutations, those with RET 634/918 had better OS (HR: 0.28, 95% CI: 0.12-0.69). Other germline mutations, including SDHB, did not exhibit worse OS than patients with metastasis and sporadic disease.

Conclusions: OS rates correlated with the recently developed AJCC TNM staging and was not worse in hereditary disease. Stage IV disease exhibited a significantly shorter OS compared with stages I-III. Future staging systems could be adjusted to better separate stages I and II.

Keywords: RET; SDHB; AJCC 8th edition cancer staging manual; paraganglioma; pheochromocytoma; prognosis.