The Role of Serum 5-HIAA as a Predictor of Progression and an Alternative to 24-h Urine 5-HIAA in Well-Differentiated Neuroendocrine Neoplasms

SIMPLE SUMMARY: 5-hydroxyinoloacetic acid (5HIAA) is the breakdown product of serotonin and it is traditionally measured in 24-h urinary samples in patients with neuroendocrine neoplasms (NENs). 5HIAA measurement in patient serum has recently become available and has started replacing the traditional method in many centers, as it is more convenient and often preferred by patients. In this prospective, single center study, we aimed to investigate the clinical utility of serum 5HIAA for diagnostic purposes and disease surveillance in a cohort of patients with well-differentiated NENs. Our analysis confirmed an association between serum 5HIAA and the presence of liver metastases, as well as the extent of liver tumor involvement, demonstrating that the biomarker becomes positive in advanced disease stages. However, there was no evident association between a change in serum 5HIAA and change in disease status. Additionally, with respect to diagnostic purposes as compared to urinary 5HIAA testing, there was a substantial agreement between the two methods. In conclusion, serum 5HIAA performs well compared to urinary testing for diagnostic purposes but does not seem adequate as a solo biomarker of disease progression. ABSTRACT: Our aim was to investigate the clinical utility of serum 5HIAA for disease surveillance and diagnostic purposes in a cohort of patients with well-differentiated neuroendocrine neoplasms (WD-NENs). Forty-eight patients with WD-NENs and concurrent serum and urinary 5HIAA testing, as well as CT/MRI imaging, were included. Analysis of matching-pairs did not reveal any association between RECIST 1.1 responses and changes in serum 5HIAA levels (p = 0.673). In addition, no correlation was evident between RECIST 1.1 responses and >10%, >25% or >50% changes in serum 5HIAA levels (Fisher’s exact test p = 0.380, p > 0.999, and p > 0.999, respectively). The presence of liver metastases and extensive liver tumor involvement were associated with higher serum 5HIAA levels (p = 0.045 and p = 0.041, respectively). We also confirmed a strong linear correlation between the measurements of serum and urine 5HIAA (n = 24, r = 0.791, p < 0.0001). The concordance rate of serum and urinary 5HIAA positivity at standardized laboratory cut-offs was 75%. In patients with normal renal function tests, the concordance between the two methods was as high as 89%, and a sensitivity and specificity of 80% and 88.9%, respectively, was evident (Cohen’s kappa coefficient = 0.685). In conclusion, serum 5HIAA performs well compared to urinary testing for diagnostic purposes, mainly in advanced disease stages, and corresponds well to liver tumor burden. However, it is not adequate to predict tumor progression.