NETest: A Systematic Review Focusing on the Prognostic and Predictive Role

Abstract

The NETest is a standardized and reproducible liquid biopsy for neuroendocrine tumors (NETs). It evaluates the expression of 51 NET genes by real-time polymerase chain reaction, providing an accurate molecular profile of the neoplasm. Diagnostic utility of NETest has been widely demonstrated, while its role in predicting prognosis and treatment response is less studied. This systematic review aims to collect and discuss the available evidence on the prognostic and predictive role of NETest, trying to answer 3 questions, frequently raised in clinical practice. <i>Is NETest able to differentiate stable from progressive disease?</i> Increased NETest levels (at least >40%) correlate with disease progression. <i>Is NETest able to predict tumor progression and tumor response to treatment?</i> Some studies demonstrated that the baseline NETest score >33–40% could predict tumor progression. Moreover, NETest performed after treatment (as peptide receptor radionuclide therapy) could predict treatment response also before radiological findings, since the decrease or stability of NETest score predicts tumor response to treatment. <i>Is NETest able to evaluate tumor recurrence risk after surgery?</i> NETest can predict surgical treatment outcome detecting minimal residual disease after radical surgery, which is characterized by a lower but positive NETest score (20–40%), while a higher score (>33–40%) is associated with nonradical surgery. In conclusion, in addition to its demonstrated diagnostic role, this systematic review highlights the efficacy of NETest to assess disease status at the moment of the NETest execution and to predict tumor recurrence after surgery. The efficacy for other applications should be proven by additional studies.

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“…Samples that exhibit lower tumor activity strongly indicate indolent tumor behavior. These metrics are in line with our and other previous cross-sectional studies, but the reproducibility of NETest scores in individuals has not been studied before since long-term data on repeated NETest samples (>1 year) were missing ( 19 , 22 , 23 , 24 ). AUROC analysis of consecutive samples showed a shift in test accuracy during years of disease evolution and a decrease in predictive value, putting the NETest role as follow-up marker into a new perspective.…”

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“…In the field of biochemical markers, growing attention is paid to NETest, an application of liquid biopsy in the field of NET, which has also demonstrated a prognostic role ( 36 ). In a larger study on the personalized approach to patients affected by neuroendocrine neoplasms, Frilling et al.…”

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