Prognostic impact of anatomic site in pheochromocytomas and paragangliomas: a population-based cohort study

The prognostic importance of tumor location in pheochromocytomas and paragangliomas (PPGLs) remains controversial. This study aimed to assess whether anatomic site independently influences survival in PPGLs.

Retrospective, population-based cohort using SEER 17 (2000-2022).

Patients with histologically confirmed PPGLs were categorized by the primary site as adrenal gland, head and neck, thorax, or abdomen. Overall and cancer-specific survival rates were analyzed using Kaplan-Meier and multivariable Cox models, including stage-stratified analyses. Propensity score matching (PSM) was performed to minimize confounding.

Among 1468 patients, 55.9% had adrenal, 17.6% abdominal, 13.6% head and neck, and 12.8% thoracic tumors. Survival outcomes varied by site (P = .004), with head and neck PGLs showing the most favorable prognosis. Multivariable and stage-stratified models revealed no independent impact of site in localized disease, but significant differences emerged in regional and metastatic stages: head and neck tumors demonstrated superior outcomes in regional disease, while adrenal pheochromocytomas exhibited the poorest prognosis in distant disease (HR 2.26, 95% CI 1.14-4.48). PSM analyses confirmed that survival equivalence between adrenal and head and neck tumors in early-stage disease diverged upon metastasis.

The prognostic effect of anatomic site in PPGLs is stage-dependent. While location does not influence outcomes in localized disease, it becomes clinically meaningful with progression-favoring head and neck tumors and disadvantaging adrenal primaries in advanced stages. Incorporating site into stage-aware risk stratification and tailoring multimodal care for high-risk thoraco-abdominal/adrenal disease are warranted. Prospective, genotype-annotated registries should validate and refine these findings.