Limited value for urinary 5-HIAA excretion as prognostic marker in gastrointestinal neuroendocrine tumours

Objective

To determine if urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion is of prognostic value for overall survival (OS) in patients with a gastrointestinal neuroendocrine tumour (NET) and to compare the prognostic value with patient characteristics, ENETS/WHO grading, ENETS TNM staging and biomarkers.

Design and methods

Data was collected from patients with a gastrointestinal NET or a NET with gastrointestinal metastases and available 5-HIAA excretion in 24-h urine samples. Laboratory results were stratified for urinary 5-HIAA and chromogranin A (CgA): <2x upper limit of normal (ULN), 2–10x ULN, or >10x ULN. For neuron-specific enolase (NSE), this was the reference range or >1x ULN. OS was compared using Kaplan–Meier and log-rank tests, and hazard ratios were calculated using Cox regression for univariate and multivariate analyses.

Results

A total of 371 patients were included, 46.6% female with a mean age of 59.9 years. OS was shortest in patients with urinary 5-HIAA excretion >10x ULN vs reference range (median 83 months vs 141 months, P = 0.002). In univariate analysis, urinary 5-HIAA excretion >10x ULN was a negative predictor (HR 1.62, 95% CI: 1.09–2.39). However, in multivariate analysis, only age (HR 1.04, 95% CI: 1.01–1.08), grade 3 disease (HR 5.09, 95% CI: 2.20–11.79), NSE >1x ULN (HR 2.36, 95% CI: 1.34–4.14) and CgA >10x ULN (HR 3.61, 95% CI: 1.56–8.34) remained as the predictors.

Conclusion

Urinary 5-HIAA excretion >10x ULN is a negative predictor for OS. However, when added to other biomarkers and grading, it is no longer a predictor for OS. Therefore, it should only be determined to assess carcinoid syndrome and not for prognostic value.

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