NETs usually express somatostatin receptors; therefore, somatostatin expression can be used both diagnostically and therapeutically [10]. Somatostatin receptor imaging (¹¹¹In-DTPA-octreotide or preferably ⁶⁸Ga-DOTATATE) can be used for initial staging, follow-up and selecting patients for peptide receptor radionuclide therapy (PRRT) [11, 12]. According to the localization of the primary tumour, computerised tomography and/or magnetic resonance imaging (MRI) should also be used for diagnosis and staging. Ultrasound and endoscopic ultrasound can be used when necessary as complementary examinations. 5-Fluorodeoxyglucose (FDG)-positron emission tomography (PET) can be used in diagnosis, staging and follow-up of aggressive, poorly differentiated NETs. FDG-PET may also show transformation to aggressive biological behaviour [11, 12]. The role of newer PET tracers warrants further validation for routine clinical practice. Endoscopic evaluation of the patients with esophagogastroduodenoscopy, colonoscopy, double-balloon enteroscopy or capsule endoscopy is critical according to the localization of the primary tumour and also in patients with primary unknown metastatic neuroendocrine tumour or carcinoma.

Surgery is the only potentially curative treatment modality. Surgery should be considered for patients with early-stage disease, in patients with locoregional and resectable metastatic disease and in some selected symptomatic patients [13]. Resection of the primary tumour and metastasectomy should be considered for all suitable patients. However, surgery can not be used, because many patients are diagnosed at an advanced stage. Hence, medical treatment is necessary for both symptom and tumour control. Since somatostatin analogues have provided critical symptom control which was once the main reason for significant morbidity and mortality, now tumour bulk-related complications have become the leading cause for death [14]. The main clinical symptoms are pain, obstruction, diarrhoea, hypoglycaemia symptoms, hyperglycaemia, weight loss and carcinoid syndrome findings. Clinical symptoms may vary according to functionality of the tumour and depend on the localization and size of the tumour. The majority of these findings can be eliminated by treatment of the tumour. If carcinoid symptoms are present, somatostatin analogues, interferon, symptomatic treatment for diarrhoea, mammalian target of rapamycin (mTOR) inhibition and appropriate treatments can be used.

More patients are diagnosed at earlier and asymptomatic stage, and more non-functional tumours are detected with the aid of widespread use of improved diagnostic and pathological tools, coupled with increased awareness of the public and medical community. However, this disease is still diagnosed more commonly at advanced stage, making cure difficult to provide. The good side of the story is that the outcome of patients with NET is becoming more favourable with increased survival rates although cure may not be possible [1].

In addition to early diagnosis, improved surgical techniques can be used either aggressively or conservatively according to the presentation of the case [15, 16]. There are reported series of successful liver transplantation in selected cases, although the criteria for liver transplantation have not yet been fully established for NETs. Especially in cases with removed primary tumours, liver-directed therapies, ablation methods such as radio-frequency ablation (RFA), cryotherapy, radiosurgery or blant embolization and chemoembolization or radioembolization can be offered where surgery is not amenable. PRRT can be used in patients with well-differentiated low-grade NETs if positive for somatostatin receptor imaging. PRRT can be considered independently from primary tumour site in both functional and non-functional tumours. ¹⁷⁷Lu-DOTA-Tyr3-octreotate is preferred as it has less renal toxicity and higher somatostatin receptor 2 affinity. Response rates are higher in PNETs in comparison to small intestinal NETs [17].

Besides symptom control, somatostatin analogues improve the patient’s quality of life and provide the control of tumour progression in NETs [10]. Somatostatin analogues, octreotide LAR and lanreotide, can be used in functional and non-functional, well-differentiated gastrointestinal and pancreatic NETs for anti-proliferative purposes [18, 19].

Interferon (IFN) has been used alone and in combination with chemotherapy and somatostatin analogues for both symptom and tumour control. IFN can be used in selected cases as salvage therapy.

Systemic chemotherapy is more effective in patients with a rapidly progressive disease or a tumour with high proliferation rate and aggressive pathological features. Combination chemotherapy is more effective than single-agent chemotherapy in NETs. The role of chemotherapy is relatively established for pancreatic NETs and for poorly differentiated tumours. There is a strong need for data to define the role of adjuvant treatment in low- or intermediate-degree tumours that are surgically resected [1].