SUN-506 - Quantitative Metadrenaline Burden and Tumor Characteristics Predict Prognosis in Phaeochromocytoma and Paraganglioma: A 12-Year Single Centre Cohort Study

Background
Risk stratification in phaeochromocytoma and paraganglioma (PPGL) remains difficult. Existing models show moderate accuracy and may require genetic testing, which can be unavailable or delayed. Although plasma metadrenalines are central to diagnosis, they are not used quantitatively for risk prediction. We evaluated whether biochemical burden and routine clinical features predict metastasis and all-cause mortality in PPGL.

Method
We analysed 80 surgically treated adult PPGL patients (70 phaeochromocytoma, 10 paraganglioma) at our centre from 2012–2023. Pre-operative plasma normetadrenaline (NMA), metadrenaline (MA) and 3-methoxytyramine (3-MT) were measured via liquid chromatography tandem mass spectrometry and normalised to upper limits of normal (ULN), providing an assay-independent measure of dominant secretory activity. Biochemical burden (BioMax) was defined as the maximum fold ULN among 3 plasma metadrenalines. Variables included tumour size, central necrosis, Ki67 index, age and gender. ROC Youden analysis identified optimal cut-offs for BioMax (≥6× ULN) and size (≥7 cm). A novel score - NBS (Necrosis, BioMax ≥6× ULN, Size ≥7 cm; range 0-3) was derived. Firth penalised logistic regression and ROC analysis with 1000-bootstrap validation were done.

Results
Median follow-up was 4 years (IQR 2-7), age 59 years (IQR 51-71) and 54% was male. Metastasis occurred in 13% overall, with similar rates in phaeochromocytoma (13%) and paraganglioma (10%). Metastatic tumours were larger (median 8.1 vs 3.5 cm, p< 0.001), more often necrotic (80% vs 7%, OR 52, p< 0.001), and had higher BioMax (median 20.2× vs 3.4× ULN, p< 0.001). Other variables were not significant. NMA showed 100% sensitivity but low specificity (19%). 3-MT had high specificity (86%) and lower sensitivity (75%). MA showed low sensitivity (20%) and specificity (49%). Tumour size and BioMax showed good discrimination individually (both AUC 0.87).

The NBS score demonstrated excellent discrimination (AUC 0.95, 95% CI 0.91-0.99). At threshold ≥2, sensitivity, specificity, and accuracy were 90%, with NPV 98% and PPV 56%. Metastatic risk increased stepwise (0%, 5%, 33%, 86%) across scores 0-3. All-cause mortality was 18.8%, significantly associated with metastasis (60% vs 13%, OR 10, p< 0.001), and higher with NBS ≥2 vs < 2 (40% vs 14%, OR 4, p=0.03).

Conclusion
BioMax may reflect aggressive PPGL phenotype. Unlike existing models, NBS offers a simple yet strong prognostic tool for timely surveillance.