RESUMO
OBJECTIVE: New clinical prognostic tools are needed to select the population of patients with neuroendocrine tumors (NETs) that have a high risk of disease progression and disease-specific mortality (DSM). Biochemical biomarker doubling time (DT) is used clinically for prognosis prediction in several solid malignancies. The aim of the current study was to determine whether 24-hour urinary 5-hydroxyindoleacetic acid (5-HIAA) level DT has any prognostic utility in patients with NETs. METHODS: Patients with NETs were enrolled in a prospective study with comprehensive biochemical analysis. The current analysis included 90 subjects with increasing 5-HIAA levels in two consecutive measurements. DT was calculated using the Schwartz equation. The primary outcome measures were DSM and disease progression. RESULTS: 5-HIAA DT of <434 days was associated with a higher rate of DSM ( P = .02), with positive and negative predictive values for DSM of 75 and 77%, respectively. The difference in DSM was accounted for mainly by patients with small intestine or unknown primary NET ( P = .01). In addition, a shorter 5-HIAA DT in patients with small intestine or unknown primary NET was associated with a higher risk of disease progression both in univariate ( P = .001) and multivariable analyses (hazard ratio, 15.8; 95% confidence interval, 1.3 to 198.0; P = .03). CONCLUSION: 5-HIAA DT may be used as a risk stratification tool in patients with small intestine NET or NET of unknown primary after it is validated in an independent cohort and can assist in identifying patients with a high risk for disease progression and DSM. ABBREVIATIONS: CT = computed tomography; DSM = disease-specific mortality; DT = doubling time; 5-HIAA = 5-hydroxyindoleacetic acid; MRI = magnetic resonance imaging; NET = neuroendocrine tumor; NETUP = neuroendocrine tumor of unknown primary; PET = positron emission tomography; PFS = progression-free survival; PNET = pancreatic neuroendocrine tumor; ROC = receiver operating characteristic; SINET = small-intestine neuroendocrine tumor.
