Locally Advanced Disease and Clinical Outcomes of Pheochromocytomas and Paragangliomas: Insights from a Multicenter Study
In brief
Local invasion raises recurrence from 6% to 17% in pheochromocytomas and paragangliomas
In this retrospective study of 389 patients, persistent or recurrent disease occurred in 17.1% of those with locally invasive tumors, versus 6.1% without invasion. Local invasion also predicted poorer outcomes beyond tumor stage, while patients with both local invasion and higher Ki-67 had 68.5% five-year disease-free survival. The findings may sharpen risk assessment, but need further evaluation.
- Journal
- Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists (Q1)
- Published
- 15 October 2026
- Study design
- Cohort / observational study
- Evidence level
- Level 3, Low (CEBM 3b)
- Authors
- Buket Busra Icin, Ozden Uzun, Bekir Cakir, Belma Ozlem Tural Balsak, Narin Nasiroglu İmga, Lala Soltanova, et al.
- PMID
- 42880592
- DOI
- 10.1016/j.eprac.2026.10.005
Why clinicians should know about it
- Picked for Pathology and Forensic Medicine (top studies of the week, 18 October 2026): Locally advanced disease predicts outcomes in PPGLs
Abstract
OBJECTIVE: To evaluate the prognostic significance of locally advanced disease (LAD) in patients with pheochromocytomas and paragangliomas (PPGLs). METHODS: We retrospectively analyzed 389 patients with histopathologically confirmed PPGLs from 19 tertiary centers. LAD was defined as capsular, periadrenal fat, adjacent-organ, or vascular invasion. Persistent/recurrent disease was the composite primary endpoint. The prognostic value of LAD was further assessed after excluding patients with distant metastatic disease at diagnosis, in patients with stage I-II disease, and in combination with Ki-67 labeling index (LI) ≥3%. RESULTS: LAD was identified in 111 patients (28.5%). Persistent/recurrent disease occurred in 17.1% and 6.1% of patients with and without LAD, respectively (p<0.001), with corresponding 5-year disease-free survival (DFS) rates of 81.8% and 93.4% (log-rank p<0.001). LAD remained independently associated with persistent/recurrent disease in multivariable analysis (HR, 3.64; 95% CI, 1.55-8.52; p=0.003). Its prognostic association persisted after excluding patients with distant metastatic disease at diagnosis. Among patients with stage I-II disease, 5-year DFS was 84.8% and 95.5% with and without LAD, respectively (log-rank p=0.014), and adding LAD to the TNM-only model significantly improved model fit (likelihood-ratio p=0.025). Patients with both LAD and Ki-67 LI ≥3% had a 5-year DFS of 68.5%. CONCLUSION: LAD was associated with unfavorable outcomes in PPGLs and provided additional prognostic information beyond TNM stage in stage I-II disease. Combined assessment of local invasiveness and proliferative activity warrants further evaluation for risk stratification.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.