title: Limited value for urinary 5-HIAA excretion as prognostic marker in gastrointestinal neuroendocrine tumours.
abstract: 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.
  
  
  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): <2× upper limit of normal (ULN), 2-10× ULN, or >10× ULN. For neuron-specific enolase (NSE), this was the reference range or >1× 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 >10× ULN vs reference range (median 83 months vs 141 months, P = 0.002). In univariate analysis, urinary 5-HIAA excretion >10× 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 >1× ULN (HR 2.36, 95% CI: 1.34-4.14) and CgA >10× ULN (HR 3.61, 95% CI: 1.56-8.34) remained as the predictors.
  
  
  CONCLUSIONS
  Urinary 5-HIAA excretion >10× 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.
authors.affiliation: Department of Internal MedicineSector Endocrinology, ENETS Centre of Excellence, Erasmus MC Cancer Institute, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Wouter T
authors.initials: WT
authors.lastname: Zandee
authors.affiliation: Department of Internal MedicineSector Endocrinology, ENETS Centre of Excellence, Erasmus MC Cancer Institute, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Kamp
authors.affiliation: Department of Internal MedicineSector Endocrinology, ENETS Centre of Excellence, Erasmus MC Cancer Institute, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Roxanne C S
authors.initials: RC
authors.lastname: van Adrichem
authors.affiliation: Department of Internal MedicineSector Endocrinology, ENETS Centre of Excellence, Erasmus MC Cancer Institute, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Feelders
authors.affiliation: Department of Internal MedicineSector Endocrinology, ENETS Centre of Excellence, Erasmus MC Cancer Institute, Erasmus MC, Rotterdam, The Netherlands w.w.deherder@erasmusmc.nl.
authors.forename: Wouter W
authors.initials: WW
authors.lastname: de Herder
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000652:urine; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000652:urine; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000652:urine*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018358:Neuroendocrine Tumors / Q000175:diagnosis* / Q000401:mortality / Q000652:urine; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D006897:Hydroxyindoleacetic Acid