Urinary Catecholamines Predict Relapse During Complete Remission in High-Risk Neuroblastoma.

Purpose: Urinary catecholamine metabolites are well-known biomarkers for the diagnosis (Dx) of neuroblastoma, but their clinical significance in determining therapy response during treatment is not well established. Therefore, catecholamines are not included in criteria for assessing response and complete remission (CR). This study investigated the use of urinary catecholamines in response monitoring and predicting survival outcomes.

Methods: From 2005 to 2021, a panel of eight urinary catecholamines were measured in patients with high-risk neuroblastoma at Dx and at standard evaluation moments during treatment. At the same time points, response and CR were assessed according to the revised International Neuroblastoma Response Criteria.

Results: The total cohort consists of 153 high-risk patients, and at least one of the eight metabolites was elevated (ie, catecholamine status positive) in 141 of 146 (97%), 104 of 128 (81%), and 39 of 69 (57%) patients at Dx, postinduction, and at CR, respectively. Primary tumor resection significantly reduced catecholamine levels (P < .01). A positive catecholamine status at Dx, during treatment, and at the end of treatment was not significantly associated with event-free survival (EFS) or overall survival (OS). However, in patients who achieved CR, those with a positive catecholamine status had poor EFS (38% v 80%, respectively; P < .01) and OS (52% v 86%, respectively; P = .01) compared with those with a negative catecholamine status. Notably, 3-methoxytyramine levels at CR seem to be a prognostic marker for poor OS (hazard ratio, 7.5 [95% CI, 2.0 to 28.6]).

Conclusion: Catecholamine measurements contribute to the assessment of CR and identifies patients with high-risk neuroblastoma with an increased risk of relapse and death.