NETs are a diverse family of tumours arising from neuroendocrine cells throughout the GI tract, pancreas, and lungs. They range from incidentally discovered indolent tumours to aggressive, hormone-secreting malignancies. Expert diagnosis, grading, and MDT-led treatment are essential — and outcomes are often far better than patients expect.
Neuroendocrine tumours (NETs) arise from specialised neuroendocrine cells — cells with properties of both nerve cells and endocrine (hormone-secreting) cells — found throughout the GI tract, pancreas, lungs, and other organs. They are a heterogeneous family of tumours ranging from tiny, indolent lesions to aggressive, spreading malignancies.
NETs are classified as functional (secreting hormones that cause characteristic clinical syndromes) or non-functional (no active hormones — often found incidentally). The most important distinction is between well-differentiated NETs (G1/G2/G3) and poorly differentiated neuroendocrine carcinomas (NEC).
Grade (Ki-67 index) is the single most important prognostic factor — adequate biopsy with immunohistochemistry is mandatory before treatment planning.
NETs arise at multiple sites — each with specific subtypes, hormonal syndromes, and surgical approaches.
The grade of a NET — determined by Ki-67 proliferation index and mitotic rate on biopsy — is the single most important factor determining prognosis and treatment.
| Grade | Ki-67 Index | Mitotic Rate | Behaviour & Treatment |
|---|---|---|---|
G1 — Low Grade | <3% | <2/10 HPF | Indolent. Slow-growing. Often present for years before diagnosis. Excellent long-term prognosis. 10-year survival >80% for localised disease. |
G2 — Intermediate Grade | 3–20% | 2–20/10 HPF | Intermediate behaviour. Still well-differentiated — responds to SSA and surgery. Everolimus or PRRT for progressive disease. 5-year survival 60–75% depending on stage. |
G3 — High Grade (Well-Diff.) | >20% | >20/10 HPF | Aggressive but still shows neuroendocrine differentiation. PRRT considered. Chemotherapy for rapidly progressive disease. Better prognosis than NEC. |
NEC — Neuroendocrine Carcinoma | >20% (often >55%) | High | Poorly differentiated — treated like small cell carcinoma with platinum-based chemotherapy. Poor prognosis. Urgent treatment required. |
The clinical syndromes caused by hormone-secreting NETs are distinctive — knowing them leads to early diagnosis and effective treatment.
Peptide Receptor Radionuclide Therapy delivers targeted radiotherapy directly to somatostatin receptor-expressing NETs. Lu-177 DOTATATE homes in on NET cells and delivers a lethal dose of radiation precisely to the tumour, sparing surrounding normal tissue.
The landmark NETTER-1 trial (NEJM 2017) showed PRRT significantly improved progression-free survival and response rate compared to high-dose octreotide — with low toxicity. PRRT is now standard of care for progressive, somatostatin receptor-positive G1/G2 midgut NETs.
NET diagnosis requires biochemical tests, specialised imaging, and tissue biopsy with IHC. The Ga-68 DOTATATE PET-CT has revolutionised NET staging.
NET treatment is highly individualised — depending on primary site, grade, stage, functionality, and patient fitness. Every patient should be discussed at a specialist NET MDT before treatment begins.
Yes — but they behave very differently from conventional cancers. Well-differentiated NETs (G1/G2) typically grow slowly, may be present for years before diagnosis, and carry significantly better long-term prognosis than adenocarcinomas. Many patients with metastatic well-differentiated NETs live 5–10+ years with good quality of life. However, poorly differentiated neuroendocrine carcinomas (NEC) are aggressive and require urgent treatment. The grade (Ki-67 index) is the single most important prognostic factor.
Carcinoid syndrome — flushing, diarrhoea, wheezing, and right-sided heart disease — is caused by serotonin and other hormones secreted by the tumour. Crucially, it only occurs when liver metastases are present, because the liver normally inactivates hormones from the portal circulation. Treatment involves somatostatin analogues (octreotide LAR), which dramatically control symptoms in most patients.
PRRT (Lu-177 DOTATATE / Lutathera) delivers targeted radiotherapy to somatostatin receptor-positive tumours intravenously. To qualify: the tumour must express somatostatin receptors (confirmed on Ga-68 DOTATATE PET-CT), the NET must be well-differentiated (G1/G2), and standard therapies must have been tried or considered. The NETTER-1 trial showed significant improvement in progression-free survival.
Most small, incidentally discovered, low-grade NETs are biologically indolent. Small (<2 cm) G1 pancreatic NETs may be managed with active surveillance with 6-monthly CT. Small rectal NETs (<1 cm) are treated with endoscopic resection — effectively cured. Every incidental NET must be discussed at a specialist MDT before any management decision.
Yes — Multiple Endocrine Neoplasia type 1 (MEN1) is the most important hereditary NET syndrome, causing pNETs (particularly gastrinomas), parathyroid adenomas, and pituitary tumours. All patients with gastrinoma should be screened for MEN1. Other syndromes: VHL (pancreatic NETs), NF1 (duodenal somatostatinoma). Genetic testing is recommended for young patients, multiple tumours, or family history.
NETs are well-differentiated, express somatostatin receptors, grow slowly, and respond to SSA and PRRT. NECs are poorly differentiated, aggressive, do not express somatostatin receptors, and require platinum-based chemotherapy. The Ki-67 index and morphology on biopsy distinguish them. NETs with Ki-67 20–55% and well-differentiated morphology are G3 well-differentiated NETs — an important distinction from NEC.
Bring your biopsy report (with Ki-67), CT scan, Ga-68 DOTATATE PET-CT if done, and biochemical results (CgA, 5-HIAA, specific hormones). Dr. Gore will review and present your case at MDT before recommending a treatment plan.