Introduction: neuroblastoma accounts for 10% of pediatric malignancies and is responsible for 15% of pediatric cancer-related deaths. Vanillylmandelic acid (VMA) and homovanillic acid (HVA) are commonly analyzed in urine of neuroblastoma patients, however, their diagnostic sensitivity is quite low and their correlation with clinical outcome is still controversial. Other catecholamines metabolites have hardly been studied and for diagnostic purposes, analysis of a panel of catecholamine metabolites might be more accurate. Therefore, we performed in-depth analysis of the diagnostic sensitivity of catecholamine metabolites at time of diagnosis and their correlation with clinical outcome.
Patients and methods: retrospective study of urinary metabolites (VMA, HVA, 3-methoxytyramine, dopamine, epinephrine, metanephrine, norepinephrine and normetanephrine) from 301 neuroblastoma patients at diagnosis.
Results: normetanephrine was the most sensitive diagnostic metabolite with sensitivity of 89%, improving to 95% when all 8 metabolites were combined. Especially 3-methoxytyramine and dopamine correlated with clinical and biological neuroblastoma features such as INSS stage and MYCN amplification. HVA and 3-methoxytyramine were significant independent risk factors for event free survival and overall survival. Patients with elevated 3-methoxytyramine had worse 5-years event free survival (29.2% vs. 76.3%, p < 0.001) and overall survival (35.5% vs. 84.1%, p < 0.001). Elevated 3-methoxytyramine also correlated with outcome within clinical subgroups such as patients with stage 4 disease (5-year OS: 25.0% and 58.3%, p < 0.001). In addition, patients with elevated 3-methoxytyramine had a worse prognosis regardless of their HVA status.
Conclusions: our study demonstrates that analysis of a panel of urinary catecholamine metabolites panel, comprising 8 markers, during diagnostic work-up ensures the highest diagnostic sensitivity and can assist in estimating the clinical outcome.