Management Of Pancreatic Neuroendocrine Tumors Research Articles

Robotic Versus Laparoscopic Versus Open Surgery for Non-Metastatic Pancreatic Neuroendocrine Tumors (pNETs): A Systematic Review and Network Meta-Analysis

Background: This systematic review, using pairwise and network meta-analyses, aimed to compare the intraoperative, short-term, and long-term postoperative outcomes of minimally invasive surgery (MIS) and open surgery (OS) for the management of pancreatic neuroendocrine tumors (pNETs). Methods: Studies reporting on the effects of robotic, laparoscopic, and open surgery on pNETs published before November 2023 on PubMed, Scopus, and CENTRAL were analyzed. Results: Thirty-two studies with 5379 patients were included in this review, encompassing 2251 patients undergoing MIS (1334 laparoscopic, 508 robotic, and 409 unspecified MIS) and 3128 patients undergoing OS for pNETs management. Pairwise meta-analysis revealed that the MIS group had a significantly shorter length of hospital stay ((a low certainty of evidence), MD of −4.87 (−6.19 to −3.56)); less intraoperative blood loss ((a low certainty of evidence), MD of −108.47 (−177.47 to −39.47)); and decreased tumor recurrence ((a high certainty of evidence), RR of 0.46, 95% CI (0.33 to 0.63)). Subgroup analysis indicated a higher R0 resection rate and prolonged operative time for laparoscopic surgery than for OS. The network meta-analysis ranked the robotic approach as superior in terms of the length of hospital stay, followed by the laparoscopic and OS arms. Furthermore, it favored both MIS approaches over OS in terms of the R0 resection rate. No significant differences were found in severe postoperative complications, postoperative fistula formation, mortality, readmission, reoperation, or conversion rates. Conclusions: This review supports the safety of MIS for the treatment of pNETs. However, the varying certainty of evidence emphasizes the need for higher-quality studies.

Surgical management of pancreatic neuroendocrine tumors – An EYSAC and E-AHPBA international survey of current practice

IntroductionPancreatic neuroendocrine tumors (pNET) exhibit a wide spectrum of clinical behavior, which makes their assessment and management quite challenging. The purpose of this study was to comprehensively assess the existing treatment landscape for patients with pNET. Materials and methodsThe study was conducted with the support of the ESSO-EYSAC Research Academy in collaboration with the E-AHPBA. An online survey was distributed via email and social media to surgical networks across Europe and beyond (September 1–30, 2023). ResultsOverall, 155 complete responses were obtained. A specialized NET tumor board was present at the institutions of 94 (61 %) of the study participants. The most frequently applied guidelines were from ENETS (n = 97; 63 %), NCCN (n = 74; 48 %), and ESMO (n = 53; 34 %). For resectability, similar criteria as in pancreatic ductal adenocarcinoma were used by 111 (72 %) participants, even though 116 (75 %) participants believed that pNET/pNEC should have their own resectability criteria. Most respondents used somatostatin analogues (n = 126; 81 %) and chemotherapy (n = 85; 55 %) as neoadjuvant treatments, followed by molecularly targeted agents (n = 45; 29 %) and PRRT (n = 37; 24 %). Only 17 (11 %) participants agreed/strongly agreed that the management of pNET/pNEC is sufficiently addressed in surgical education programs. ConclusionThis international survey highlighted areas for improvement in the care of pNET, namely the lack of pNET-specific resectability criteria and educational programs addressing pNET management.

Contemporary Approaches to the Surgical Management of Pancreatic Neuroendocrine Tumors.

The incidence of pancreatic neuroendocrine tumors (PNETs) is on the rise primarily due to the increasing use of cross-sectional imaging. Most of these incidentally detected lesions are non-functional PNETs with a small proportion of lesions being hormone-secreting, functional neoplasms. With recent advances in surgical approaches and systemic therapies, the management of PNETs have undergone a paradigm shift towards a more individualized approach. In this manuscript, we review the histologic classification and diagnostic approaches to both functional and non-functional PNETs. Additionally, we detail multidisciplinary approaches and surgical considerations tailored to the tumor's biology, location, and functionality based on recent evidence. We also discuss the complexities of metastatic disease, exploring liver-directed therapies and the evolving landscape of minimally invasive surgical techniques.

ASO Author Reflections: Accuracy and Prognostic Impact of Nodal Status on Preoperative Imaging for Management of Pancreatic Neuroendocrine Tumors.

ASO Author Reflections: Accuracy and Prognostic Impact of Nodal Status on Preoperative Imaging for Management of Pancreatic Neuroendocrine Tumors.

Endoscopic Ultrasound-Guided Local Ablative Therapies for the Treatment of Pancreatic Neuroendocrine Tumors and Cystic Lesions: A Review of the Current Literature.

Since its emergence as a diagnostic modality in the 1980s, endoscopic ultrasound (EUS) has provided the clinician profound access to gastrointestinal organs to aid in the direct visualization, sampling, and subsequent identification of pancreatic pathology. In recent years, advancements in EUS as an interventional technique have promoted the use of local ablative therapies as a minimally invasive alternative to the surgical management of pancreatic neuroendocrine tumors (pNETs) and pancreatic cystic neoplasms (PCNs), especially for those deemed to be poor operative candidates. EUS-guided local therapies have demonstrated promising efficacy in addressing a spectrum of pancreatic neoplasms, while also balancing local adverse effects on healthy parenchyma. This article serves as a review of the current literature detailing the mechanisms, outcomes, complications, and limitations of EUS-guided local ablative therapies such as chemical ablation and radiofrequency ablation (RFA) for the treatment of pNETs and PCNs, as well as a discussion of future applications of EUS-guided techniques to address a broader scope of pancreatic pathology.

Surgical Management of Pancreatic Neuroendocrine Tumors.

Pancreatic neuroendocrine tumors (PNETs) are relatively uncommon malignancies, characterized as either functional or nonfunctional secondary to their secretion of biologically active hormones. A wide range of clinical behavior can be seen, with the primary prognostic indicator being tumor grade as defined by the Ki67 proliferation index and mitotic index. Surgery is the primary treatment modality for PNETs. While functional PNETs should undergo resection for symptom control as well as potential curative intent, nonfunctional PNETs are increasingly managed nonoperatively. There is increasing data to suggest small, nonfunctional PNETs (less than 2 cm) are appropriate follow with nonoperative active surveillance. Evidence supports surgical management of metastatic disease if possible, and occasionally even surgical management of the primary tumor in the setting of widespread metastases. In this review, we highlight the evolving surgical management of local and metastatic PNETs.

Role of Endoscopic Ultrasound Ablative Therapy in Management of Pancreatic Neuroendocrine Tumors: a Systematic Review

Role of Endoscopic Ultrasound Ablative Therapy in Management of Pancreatic Neuroendocrine Tumors: a Systematic Review

Clinical features and postoperative survival in patients with sporadic versus multiple endocrine neoplasia type 1-related pancreatic neuroendocrine tumors: An international cohort study

BackgroundThe optimal surgical management of pancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1 is controversial. This study sought to compare clinicopathologic characteristics and outcomes of multiple endocrine neoplasia type 1–associated and sporadic pancreatic neuroendocrine tumors from a large multi-national database. MethodsA multi-institutional, international database of patients with surgically resected pancreatic neuroendocrine tumors was analyzed. The cohort was divided into 2 groups: those with multiple endocrine neoplasia type 1 versus those with sporadic disease. Clinicopathologic comparisons were made. Overall and disease-free survival were analyzed. Propensity score matching was used to reduce bias. ResultsOf 651 patients included, 45 (6.9%) had multiple endocrine neoplasia type 1 and 606 sporadic pancreatic neuroendocrine tumors. Multiple endocrine neoplasia type 1–associated pancreatic neuroendocrine tumors were more common in younger patients and associated with multifocal disease at the time of surgery and higher T-stage. Lymph node involvement and the presence of metastasis were similar. Total pancreatectomy rate was 5-fold higher in the multiple endocrine neoplasia type 1 cohort. Median survival did not differ (disease-free survival 126 months multiple endocrine neoplasia type 1 vs 198 months sporadic, P > .5). After matching, survival remained similar (overall survival not reached in either cohort, disease-free survival 126 months multiple endocrine neoplasia type 1 vs 198 months sporadic, P > .5). Equivalence in overall survival and disease-free survival persisted even when patients who underwent subtotal and total pancreatectomy were excluded. ConclusionMultiple endocrine neoplasia type 1–associated pancreatic neuroendocrine tumors are more common in younger patients and are associated with multifocality and higher T-stage. Survival for patients with multiple endocrine neoplasia type 1–associated pancreatic neuroendocrine tumors is comparable to those with sporadic pancreatic neuroendocrine tumors, even in the absence of radical pancreatectomy. Consideration should be given to parenchymal-sparing surgery to preserve pancreatic function.

Management of pancreatic neuroendocrine tumors in Multiple Endocrine Neoplasia Type 1 and the von Hippel Lindau syndrome

Management of pancreatic neuroendocrine tumors in Multiple Endocrine Neoplasia Type 1 and the von Hippel Lindau syndrome

Similar Outcomes in Minimally Invasive versus Open Management of Primary Pancreatic Neuroendocrine Tumors: A Regional, Multi-Institutional Collaborative Analysis.

Simple SummaryPancreatic neuroendocrine tumors (PNETs) are rare tumors of the pancreas that are often curable with surgery. Due to their rarity, it is difficult to study whether newer techniques for removing PNETs, specifically minimally invasive surgeries, are as safe and effective as open surgeries in these patients. In this study, we pooled the experience of multiple high-volume institutions who remove PNETs, and studied outcomes in open and minimally invasive surgeries. We discovered that patients receiving a minimally invasive surgery were equally likely to remain alive and without disease as patients receiving an open surgery. Additionally, there was no difference in the most common complications experienced by patients receiving these operations. Therefore, we can recommend the routine use of minimally invasive surgery techniques in appropriately selected patients with PNET, if offered by their surgeon.In pancreatic neuroendocrine tumors (PNETs), the impact of minimally invasive (MI) versus open resection on outcomes remains poorly studied. We queried a multi-institutional pancreatic cancer registry for patients with resected non-metastatic PNET from 1996–2020. Recurrence-free (RFS), disease-specific survival (DSS), and operative complications were evaluated. Two hundred and eighty-two patients were identified. Operations were open in 139 (49%) and MI in 143 (51%). Pancreaticoduodenectomy was performed in 77 (27%, n = 23 MI), distal pancreatectomy in 184 (65%, n = 109 MI), enucleation in 13 (5%), and total pancreatectomy in eight (3%). Median follow-up was 50 months. Thirty-six recurrences and 13 deaths from recurrent disease yielded 5-year RFS and DSS of 85% and 95%, respectively. On multivariable analysis, grade 1 (HR 0.07, p < 0.001) and grade 2 (HR 0.20, p = 0.002) tumors were associated with improved RFS, while T3/T4 tumors were associated with worse RFS (OR 2.78, p = 0.04). MI resection was not associated with RFS (HR 0.53, p = 0.14). There was insufficient mortality to evaluate DSS with multivariable analysis. Of 159 patients with available NSQIP data, incisional surgical site infections (SSIs), organ space SSIs, Grade B/C pancreatic fistulas, reoperations, and need for percutaneous drainage did not differ by operative approach (all p > 0.2). Nodal harvest was similar for MI versus open distal pancreatectomies (p = 0.16) and pancreaticoduodenectomies (p = 0.28). Minimally invasive surgical management of PNETs is equivalent for oncologic and postoperative outcomes.

The Role of Surgery for Pancreatic Neuroendocrine Tumors.

Pancreatic neuroendocrine tumors (PNETs) arise from endocrine pancreatic cells and comprise 3-5% of pancreatic cancers. Surgical resection is the only potentially curative option for PNETs. Surgical candidates should be carefully selected according to tumor functionality, size, location, grade, and stage. Current guidelines state that patients with neuroendocrine carcinoma may not be surgical candidates due to aggressive tumor behavior and poor prognosis, while in cases of PNET with unresectable metastatic disease, resection may be of benefit in certain patients. The current guidelines recommend resection of any size of functional PNETs and of non-functional PNETs >2 cm. Watchful waiting is recommended for patients with non-functional PNETs <1 cm. Further evidence is needed to determine whether surgery for non-functional PNETs of 1-2 cm would be of benefit or if surgery should be individualized. This review aimed to discuss the current literature on the management of PNETs and highlight the utility of surgery in treatment.

Current and New Challenges in the Management of Pancreatic Neuroendocrine Tumors: The Role of miRNA-Based Approaches as New Reliable Biomarkers.

Pancreatic neuroendocrine tumors (PanNETs) are rare tumors; however, their incidence greatly increases with age, and they occur more frequently among the elderly. They represent 5% of all pancreatic tumors, and despite the fact that low-grade tumors often have an indolent evolution, they portend a poor prognosis in an advanced stages and undifferentiated tumors. Additionally, functional pancreatic neuroendocrine tumors greatly impact quality of life due to the various clinical syndromes that result from abnormal hormonal secretion. With limited therapeutic and diagnostic options, patient stratification and selection of optimal therapeutic strategies should be the main focus. Modest improvements in the management of pancreatic neuroendocrine tumors have been achieved in the last years. Therefore, it is imperative to find new biomarkers and therapeutic strategies to improve patient survival and quality of life, limiting the disease burden. MicroRNAs (miRNAs) are small endogenous molecules that modulate the expression of thousands of genes and control numerous critical processes involved in tumor development and progression. New data also suggest the implication of miRNAs in treatment resistance and their potential as prognostic or diagnostic biomarkers and therapeutic targets. In this review, we discusses the current and new challenges in the management of PanNETs, including genetic and epigenetic approaches. Furthermore, we summarize the available data on miRNAs as potential prognostic, predictive, or diagnostic biomarkers and discuss their function as future therapeutic targets.

Clarifying the Role of Observation in the Management of Poorly Differentiated Pancreatic Neuroendocrine Tumors

Introduction: The management of pancreatic neuroendocrine tumors (PNET) varies between observation (O), pancreatic resection (PR) and enucleation (E). Currently, size, grade and location are used to determine which treatment strategy may be employed. We sought to evaluate each strategy and further clarify the role for surgery with regards to patients with poorly differentiated (PD) PNET. Method: Utilizing the National Cancer Database we identified patients with poorly differentiated PNET and stratified based upon size and management. Pearson’s Chi-square test was used to compare categorical variables. Survival analyses were performed using the Kaplan-Meier method. Multivariate analysis (MVA) was performed to identify predictors of survival. A p-value of <0.05 was considered significant. Results: We identified 3,187 patients diagnosed with poorly differentiated pancreatic neuroendocrine tumors. The median age of the cohort was 61 (18-90). Patients with tumors > 2cm demonstrated a higher incidence of node positivity compared to other cohorts p=0.01. Patients with <2cm tumors demonstrated a 5-year survival of 65% in those undergoing surgery vs 16% in those who did not, p<0.001. There was no difference in survival in those patients undergoing pancreatic enucleation vs those undergoing pancreatic resection, (median survival 102.2 months PR, vs 107.9 months PE, p=0.16). Multivariate analysis revealed age, tumor location, size, surgery, and clinical stage were predictors of survival. Conclusions: Poorly differentiated pancreatic neuroendocrine tumors exhibit high incidence of node positivity. Surgery improves survival in all patients with poorly differentiated PNET. Thus, observation has no role in the management of PD PNET.

EUS-guided radiofrequency ablation for pancreatic insulinoma: experience in 2 tertiary centers

Insulinoma is the most frequent functional neuroendocrine tumor of the pancreas, and preserving surgery is the treatment of choice. EUS-guided radiofrequency ablation (EUS-RFA) is a novel and promising technique that induces tissue necrosis of localized lesions. This article presents a preliminary clinical experience in treating pancreatic insulinomas<2 cm by EUS-RFA, focusing on safety and efficacy. The clinical course of patients with pancreatic insulinoma treated by EUS-RFA at 2 tertiary referral centers was analyzed. Between November 2017 and December 2020, 7 patients were included (6 women; mean age, 66 years). EUS-RFA was feasible in all patients with immediate hypoglycemia relief after only 1 single treatment session; 6 of 7 achieved complete response by cross-sectional imaging and remained asymptomatic (median follow-up, 21 months; range, 3-38). Three patients had minor adverse events. One elderly patient developed a large retrogastric collection 15 days after treatment and died 1 month after EUS-RFA. Management of pancreatic neuroendocrine tumors<2 cm by EUS-RFA seems to be effective with an acceptable safety profile. However, further evidence focusing on long-term survival and recurrence is needed.

Quantitative Computed Tomography Image Analysis to Predict Pancreatic Neuroendocrine Tumor Grade.

The therapeutic management of pancreatic neuroendocrine tumors (PanNETs) is based on pathological tumor grade assessment. A noninvasive imaging method to grade tumors would facilitate treatment selection. This study evaluated the ability of quantitative image analysis derived from computed tomography (CT) images to predict PanNET grade. Institutional database was queried for resected PanNET (2000-2017) with a preoperative arterial phase CT scan. Radiomic features were extracted from the primary tumor on the CT scan using quantitative image analysis, and qualitative radiographic descriptors were assessed by two radiologists. Significant features were identified by univariable analysis and used to build multivariable models to predict PanNET grade. Overall, 150 patients were included. The performance of models based on qualitative radiographic descriptors varied between the two radiologists (reader 1: sensitivity, 33%; specificity, 66%; negative predictive value [NPV], 63%; and positive predictive value [PPV], 37%; reader 2: sensitivity, 45%; specificity, 70%; NPV, 72%; and PPV, 47%). The model based on radiomics had a better performance predicting the tumor grade with a sensitivity of 54%, a specificity of 80%, an NPV of 81%, and a PPV of 54%. The inclusion of radiomics in the radiographic descriptor models improved both the radiologists' performance. CT quantitative image analysis of PanNETs helps predict tumor grade from routinely acquired scans and should be investigated in future prospective studies.

Updated Principles of Surgical Management of Pancreatic Neuroendocrine Tumours (pNETs): What Every Surgeon Needs to Know.

Simple SummaryIn this narrative review, we update the surgical management of pancreatic neuroendocrine tumours (pNETs) and highlight key elements in view of the recent literature. These tumours are rare and suffer from a lack of data and randomized controlled trials. The pNETs management is difficult due to their heterogeneity and the risks associated with pancreatic surgery. Innovative managements such as “watch and wait” strategies, parenchymal sparing surgery and minimally invasive approach are emerging. The correct use of all these therapeutic options requires a good selection of patients but also a constant update of knowledge.Pancreatic neuroendocrine tumours (pNETs) represent 1 to 2% of all pancreatic neoplasm with an increasing incidence. They have a varied clinical, biological and radiological presentation, depending on whether they are sporadic or genetic in origin, whether they are functional or non-functional, and whether there is a single or multiple lesions. These pNETs are often diagnosed at an advanced stage with locoregional lymph nodes invasion or distant metastases. In most cases, the gold standard curative treatment is surgical resection of the pancreatic tumour, but the postoperative complications and functional consequences are not negligible. Thus, these patients should be managed in specialised high-volume centres with multidisciplinary discussion involving surgeons, oncologists, radiologists and pathologists. Innovative managements such as “watch and wait” strategies, parenchymal sparing surgery and minimally invasive approach are emerging. The correct use of all these therapeutic options requires a good selection of patients but also a constant update of knowledge. The aim of this work is to update the surgical management of pNETs and to highlight key elements in view of the recent literature.

Progress in the Management of Pancreatic Neuroendocrine Tumors.

Pancreatic neuroendocrine tumors (PNETs) are a heterogeneous and orphan group of neoplasms that vary in their histology, clinical features, prognosis, and management. The treatment of PNETs is highly dependent on the stage at presentation, tumor grade and differentiation, presence of symptoms from hormonal overproduction or from local growth, tumor burden, and rate of progression. The US Food and Drug Administration has recently approved many novel treatments, which have altered decision making and positively impacted the care and prognosis of these patients. In this review, we focus on the significant progress made in the management of PNETs over the past decade, as well as the active areas of research.

Evaluation of the current treatment strategies for poorly differentiated pancreatic neuroendocrine tumors

Presenter: Jamie Glasser MS | Sarasota Memorial Cancer Institute Background: The management of pancreatic neuroendocrine tumors (PNET) varies between observation (O), pancreatic resection (PR) and enucleation (E). Currently, size, grade and location are used to determine which treatment strategy may be employed. We sought to evaluate each strategy and further clarify the role for surgery with regards to patients with poorly differentiated (PD) PNET. Methods: Utilizing the National Cancer Database we identified patients with poorly differentiated pancreatic neuroendocrine tumors and stratified based upon size and management. Mann-Whitney U and Kruskal were used to compare continuous variables and Pearson’s Chi-square test was used to compare categorical variables. Unadjusted survival analyses were performed using the Kaplan-Meier method. Multivariate analysis (MVA) was performed to identify predictors of survival. All statistical tests were two-sided and p<0.05 was considered significant. Results: We identified 3,187 patients with PD PNET with a median age of 61 (18-90). There were 84 (2.6%) patients with tumors 2 cm. There were more males than females p2cm demonstrated a higher incidence of node positivity compared to other cohorts, p2cm, p=0.01. Patients with tumors 2cm tumors, 5-year survival was 65% in those undergoing surgery vs 16% in those who did not, p<0.001. There was no difference in survival in those patients undergoing pancreatic enucleation vs those undergoing pancreatic resection, (median survival 102.2 months PR, vs 107.9 months PE, p=0.16). Multivariate analysis revealed age, tumor location, size, surgery, and clinical stage were predictors of survival. Conclusion: Poorly differentiated pancreatic neuroendocrine tumors exhibit high incidence of node positivity, even in patients with tumors < 1cm. Surgery improves survival in all patients with poorly differentiated PNET. Thus, observation has no role in the management of PD PNET.

Evaluation of the current treatment strategies for pancreatic neuroendocrine tumors: a propensity score matched analysis

Purpose: The management of pancreatic neuroendocrine tumors (PNET) varies between observation(O), pancreatic resection(PR) and enucleation(E). Currently, size, grade and location are used to determine which treatment strategy may be employed. We sought to evaluate each strategy and further clarify the role for surgery. Methods: Utilizing the National Cancer Database we identified patients with PNET and stratified based upon size < 1cm, 1-2cm and >2cm. Propensity score matching was performed by age, Charleson-Deyo score, and grade. Survival analyses was performed using the Kaplan-Meier method. A p< 0.05 was considered significant. Results: We identified 17,921 patients(< 1cm, 1214, 1-2cm, 4325, and >2cm, 12,382) with a median age of 61.5 (18-90). Tumors < 1cm and well differentiated(WD) the median and 5-year survival in the O group was not reached (NR)(77%) vs 142.6 month(87%) in the surgery groups, p< 0.04; in the 1-2 cm WD group 95.7 months and 60% vs NR and 94%, p< 0.001. Similarly in the PD tumors < 1cm the median and survival was 32.9 months and 24% in the O vs NR and 81%, p< 001; in the 1-2 cm group 14.8 months and 19% vs NR and 73%, p< 0.001. There were no differences in survival between PR or E, p=0.09. Conclusions: While observation is acceptable for the management of < 1cm WD PNET, we found an improvement in survival in the patients undergoing surgery. Enucleation and PR did not differ in overall survival. Surgery for PNET should be considered as the first line treatment of these patients.

Role of PET/CT and Therapy Management of Pancreatic Neuroendocrine Tumors.

Pancreatic neuroendocrine neoplasms (panNENs) are heterogeneous neoplasms with neuroendocrine differentiation that show peculiar clinical and histomorphological features, with variable prognosis. In recent years, advances in knowledge regarding the pathophysiology and heterogeneous clinical presentation, as well as the availability of different diagnostic procedures for panNEN diagnosis and novel therapeutic options for patient clinical management, has led to the recognition of the need for an active multidisciplinary discussion for optimal patient care. Molecular imaging with positron emission tomography/computed tomography (PET/CT) has become indispensable for the management of panNENs. Several PET radiopharmaceuticals can be used to characterize either panNEN receptor expression or metabolism. The aim of this review is to offer an overview of all the currently used radiopharmaceuticals and of the new upcoming tracers for pancreatic neuroendocrine tumors (panNETs), and their clinical impact on therapy management. [68Ga]Ga-DOTA-peptide PET/CT (SSA-PET/CT) has high sensitivity, specificity, and accuracy and is recommended for the staging and restaging of any non-insulinoma well-differentiated panNEN cases to carry out detection of unknown primary tumor sites or early relapse and for evaluation of in vivo somatostatin receptors expression (SRE) to select patient candidates for peptide receptor radiometabolic treatment (PRRT) with 90Y or 177Lu and/or cold analogs. SSA-PET/CT also has a strong impact on clinical management, leading to a change in treatment in approximately a third of the cases. Its role for treatment response assessment is still under debate due to the lack of standardized criteria, even though some semiquantitative parameters seem to be able to predict response. [18F]FDG PET/CT generally shows low sensitivity in small growing and well-differentiated neuroendocrine tumors (NET; G1 and G2), while it is of utmost importance in the evaluation and management of high-grade NENs and also provides important prognostic information. When positive, [18F]FDG PET/CT impacts therapeutical management, indicating the need for a more aggressive treatment regime. Although FDG positivity does not exclude the patient from PRRT, several studies have demonstrated that it is certainly useful to predict response, even in this setting. The role of [18F]FDOPA for the study of panNET is limited by physiological uptake in the pancreas and is therefore not recommended. Moreover, it provides no information on SRE that has crucial clinical management relevance. Early acquisition of the abdomen and premedication with carbidopa may be useful to increase the accuracy, but further studies are needed to clarify its utility. GLP-1R agonists, such as exendin-4, are particularly useful for benign insulinoma detection, but their accuracy decreases in the case of malignant insulinomas. Being a whole-body imaging technique, exendin-PET/CT gives important preoperative information on tumor size and localization, which is fundamental for surgical planning as resection (enucleation of the lesion or partial pancreatic resection) is the only curative treatment. New upcoming tracers are under study, such as promising SSTR antagonists, which show a favorable biodistribution and higher tumor-to-background ratio that increases tumor detection, especially in the liver. [68Ga]pentixafor, an in vivo marker of CXCR4 expression associated with the behavior of more aggressive tumors, seems to only play a limited role in detecting well-differentiated NET since there is an inverse expression of SSTR2 and CXCR4 in G1 to G3 NETs with an elevation in CXCR4 and a decrease in SSTR2 expression with increasing grade. Other tracers, such as [68Ga]Ga-PSMA, [68Ga]Ga-DATA-TOC, [18F]SiTATE, and [18F]AlF-OC, are also under investigation.