Gastroenteropancreatic neuroendocrine tumors in 2025: From molecular profiling to artificial intelligence-driven therapy

Table 2 Diagnostic modalities for gastroenteropancreatic neuroendocrine tumors

Diagnostic tool	Clinical use	Limitations	Key clinical indications/strengths
Chromogranin A	General NET marker	Low specificity; elevated in benign conditions	Broadly available; useful for disease monitoring and prognosis
5-HIAA (urine)	Detects serotonin-secreting NETs	Diet-dependent; limited for non-serotonin tumors	Specific for carcinoid syndrome and metastatic midgut NETs
Hormonal assays	Confirms functional NETs (e.g., insulinoma)	Not useful in non-functional NETs	Essential for diagnosis of functioning tumors (insulinoma, gastrinoma, VIPoma)
68Ga-DOTATATE PET/CT	First-line imaging for well-differentiated NETs	Requires PET facilities; limited for SSTR-negative tumors	High sensitivity and specificity for staging, PRRT selection, and follow-up
18F-FDG PET/CT	For high-grade/aggressive NETs	Poor sensitivity in low-grade NETs	Prognostic stratification and detection of dedifferentiation
CT/MRI	Anatomic localization	Radiation (CT); MRI less available	Widely accessible; useful for surveillance and surgical planning
Endoscopic ultrasound	Detects small PanNETs, allows biopsy	Invasive, operator-dependent	Best for pancreatic and duodenal NETs < 2 cm; enables tissue acquisition
NGS panel	Identifies mutations, guides treatment	Not always actionable; cost	Enables precision therapy (e.g., mTOR-pathway, DNA-repair alterations)
CtDNA	Detects tumor DNA in blood	Still experimental; low ctDNA in indolent NETs	Non-invasive molecular profiling and disease monitoring
NETest	Monitors disease activity non-invasively	Limited availability; high cost	Early detection of recurrence and therapy response prediction

5-HIAA: 5-hydroxyindoleacetic acid; PET/CT: Positron emission tomography/computed tomography; MRI: Magnetic resonance imaging; NGS: Next generation sequencing; ctDNA: Circulating tumor DNA; SSTR: Somatostatin receptor; PRRT: Peptide receptor radionuclide therapy; mTOR: Mammalian target of rapamycin.