First-Line Treatment and Standard of Care for NETS 

The discussion focused on frontline management of newly diagnosed neuroendocrine tumor (NET) patients, emphasizing the heterogeneity of these tumors and the need for individualized care. For grade 1–2, low-burden, nonfunctional tumors, observation is often appropriate to assess disease biology and pace. Functional tumors, even if low-volume, typically require somatostatin analogs (SSAs) to control symptoms. Surgery and local therapies are highlighted as frontline options for liver-dominant or debulkable disease, offering potential long-term beneﬁt. For higher-burden or symptomatic tumors, systemic therapies like capecitabine-temozolomide may be considered, especially in pancreatic NETs. A key challenge discussed is low-grade tumors lacking somatostatin receptor (SSTR) expression, where SSA use is controversial and decisions may rely on FDG PET, functional symptoms, and tumor site. Site of origin (small bowel, pancreas, lung) also inﬂuences imaging interpretation, SSTR expression likelihood, and treatment selection, reinforcing that NET management requires careful, patient-speciﬁc decision-making rather than a one-size-ﬁts-all approach.

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Explore the complexities of treating neuroendocrine tumors, focusing on patient-specific strategies and the role of somatostatin analogs.

Prognostic Factors for Neuroendocrine Tumors 

The discussion focused on the key prognostic factors guiding management of neuroendocrine tumors (NETs). Dr. Arshad emphasized tumor diferentiation and Ki-67 proliferation index as the two most critical determinants of prognosis, highlighting how well-differentiated tumors with organized morphology and low atypia generally behave more indolently than poorly differentiated ones. Dr. Hendifar and others agreed that pathologic classiﬁcation is fundamental but added that disease pace of growth rate observed on serial imaging provides essential real-world insight into tumor aggressiveness—especially given the heterogeneity of NETs that a single biopsy may not capture. Dr. Shaheen noted that somatostatin receptor (SSTR) expression is another powerful prognostic and predictive marker, for grade 1–2 and select grade 3 tumors, as it inﬂuences treatment options like PRRT. Dr. Chauhan added burden of disease, particularly liver involvement, as a key prognostic factor, explaining that patients with >50% hepatic disease often have worse outcomes due to risk of liver failure despite low tumor grade.

Experts discuss key factors influencing disease prognosis, emphasizing differentiation, growth pace, and disease burden in treatment decisions.

Role of Biomarkers in Diagnosis and Management of NETS 

The discussion centered on the evolving and often confusing role of biomarkers in neuroendocrine tumors (NETs)—described by Dr. Shaheen as the “wild west” of oncology. Experts agreed that histologic biomarkers remain foundational, distinguishing well- from poorly differentiated tumors through morphology and molecular markers such as chromogranin, synaptophysin, ATRX, DAXX, TP53, and RB. Ki-67 continues to be essential for grading and prognostication, while somatostatin receptor (SSTR) expression serves as both a diagnostic and predictive biomarker guiding the use of somatostatin analogs and radioland therapy. Next-generation sequencing (NGS) is mainly reserved for neuroendocrine carcinomas and select higher-grade NETs, performed upfront in grade 3 or when tumor behavior suggests progression or atypia; rarely is it used routinely in grade 1/2 NETs, except for speciﬁc cases like thoracic or thymic neoplasms. Chromogranin, though widely ordered in the past, is now discouraged for routine use due to poor speciﬁcity; imaging and advanced molecular markers are preferred for monitoring and management decisions.

Experts discuss the evolution of neuroendocrine tumor classification, highlighting its clinical implications and the importance of standardized treatment approaches.

Early Diagnosis of Neuroendocrine Tumors

In this discussion, neuroendocrine tumor specialists address the persistent challenge of delayed diagnosis in patients with functional NETs, notably those with carcinoid syndrome. Dr. Andrew Hendifar emphasizes that vague, slowly-progressing symptoms—such as ﬂushing, diarrhea, hypoglycemia, or even hypertension—often lead to extensive diagnostic delays, with many patients identiﬁed only at advanced, sometimes incurable stages. Contrastingly, functional tumors with more severe, acute symptoms, like insulinomas, are diagnosed earlier due to their pronounced clinical presentation. The panel highlights the ever-expanding spectrum of neuroendocrine tumor manifestations, mentioning tumor-induced, non-islet cell hypoglycemia as a rare but important entity, especially in the context of high tumor burden. Recognizing this diverse symptomatology is difficult for busy primary care providers, who manage numerous patients with overlapping, nonspeciﬁc complaints. Specialists agree that ongoing education for clinicians and patients is essential, encouraging heightened vigilance and early diagnostic strategies to improve timely detection and management of functional neuroendocrine tumors.

Experts discuss the evolution of neuroendocrine tumor classification, highlighting its impact on diagnosis, treatment, and clinical implications.

Imaging Modalities for Neuroendocrine Tumors

The discussion among neuroendocrine tumor specialists highlighted major advances in imaging that have transformed diagnosis and disease management. Dr. Chauhan emphasized two main imaging approaches: anatomic imaging (CT and MRI) and molecular imaging (DOTATATE PET). Anatomic imaging remains essential for baseline staging, assessing disease burden, and monitoring treatment response—CT is preferred for chest imaging, while MRI or liver protocols are more sensitive for hepatic lesions. DOTATATE PET provides high sensitivity and specificity (≈95–97%) for detecting neuroendocrine tumors, even small or obscure lesions, and determines somatostatin receptor expression—crucial for selecting targeted therapies. When following indolent NET patients, a sudden change in disease biology may warrant repeating a DOTA scan to assess for loss of somatostatin receptor expression, indicating possible disease progression or transformation. This approach offers a non-invasive alternative to biopsy.

Classification of Neuroendocrine Tumors

In this episode, panelists discussed classification of neuroendocrine neoplasms. Over the years, the classification of neuroendocrine neoplasms has evolved significantly, improving diagnostic accuracy and guiding clinical management. The 2010 WHO classification first introduced a universal, proliferation-based grading system using Ki-67 to categorize tumors into grades 1–3, providing a reproducible metric for prognosis and treatment selection. In 2017, the system was updated to recognize well-differentiated grade 3 neuroendocrine tumors (NETs) as distinct from poorly differentiated neuroendocrine carcinomas, with implications for therapy—such as differentiating between platinum-based and temozolomide-based regimens. By 2019, this dual-axis model of grade and differentiation was standardized across all gastroenteropancreatic NENs, improving consistency in diagnosis and imaging approaches. The 2022 WHO update further refined terminology, integrated molecular features (e.g., TP53, RB, DAXX, ATRX), and expanded classification to other endocrine organs. These updates have enhanced uniformity in pathology reporting and supported more precise, personalized treatment decisions.

Aman Chauhan, MD, a medical oncologist at the University of Kentucky, discusses future directions with Lutathera (lutetium 177-dotatate) in gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

Currently, Lutathera is a standard of care for the treatment of patients with progressive, metastatic GEP-NETs, explains Chauhan. The majority of patients respond well to Lutathera, and the median progression-free survival (PFS) is in the range of 30 to 55 months. 

However, 15% to 20% of patients with GEP-NETs do not respond to Lutathera or have inadequate responses. These patients may include those with disease in the peritoneum and those who progress rapidly following treatment with Lutathera. As such, improving Lutathera to extend the median PFS is an area of need in this space, concludes Chauhan. 

Aman Chauhan, MD, discusses future directions with Lutathera in gastroenteropancreatic neuroendocrine tumors. 



Dr. Chauhan on Future Directions With Lutathera in GEP-NETs 

Aman Chauhan, MD, a medical oncologist at the University of Kentucky, discusses key recent advances in therapeutics for patients with neuroendocrine tumors (NETs), and points to the future with ongoing combination studies.


Advances across oncology over recent years are finally beginning to trickle down into more rare tumor types, such as NETs, which generally lag behind in drug developments, Chauhan explains. More clinical trials are being conducted in NETs as well, he added. 

Two examples of such studies include combination studies that Chauhan is an investigator of. These include a phase 2 study that is evaluating the combination of telotristat ethyl (Xermelo) and Lutathera (lutetium Lu 177 dotatate) in patients with well-differentiated NETs. Moreover, Chauhan is also excited about a p

hase 1 trial of triapine and Lutathera combined as a treatment for patients with well-differentiated somatostatin receptor-positive gastroenteropancreatic NETs. 

Aman Chauhan, MD, a medical oncologist at the University of Kentucky, discusses key recent advances in therapeutics for patients with neuroendocrine tumors, and points to the future with ongoing combination studies. 

Dr. Chauhan on Key Recent Advances in Neuroendocrine Tumors

Aman Chauhan, MD, a medical oncologist at the University of Kentucky, discusses the role of ​Lutathera (

​The introduction of Lutathera has been a significant advancement in the NETs treatment paradigm, says Chauhan.

The randomized phase 3 NETTER-1 trial, which served as the basis for the regulatory approval of Lutathera in January 2018, showed superior efficacy ​with Lutathera versus high-dose octreotide ​(Sandostatin).

Notably, Lutathera is a radiopharmaceutical where ​a lutetium-177 ​isotope is attached to ​dotatate, a somatostatin analog​, says Chauhan. The agent attaches to somatostatin receptor ​2, which is abundantly found in NETs.

Per the regulatory indication, patients can receive 1 dose of ​intravenous Lutathera every 2 months,​ Chauhan explains.

The therapy continuously emits radiation, causing single​- and double​-stranded DNA damage in tumor cells, ​which kill​s the cells over a period of time, Chauhan concludes.

Aman Chauhan, MD, a medical oncologist at the University of Kentucky, discusses the role of ​Lutathera in neuroendocrine tumors. 

Dr. Chauhan on the Role of Lutathera in NETs

Aman Chauhan, MD, a medical oncologist at University of Kentucky, discusses sequencing decisions when treating patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

Currently, sequencing for patients with GEP-NETs is largely dictated by the presentation or degree of tumor progression. Patients with metastatic disease, especially bone metastases who are symptomatic, would likely be treated with peptide receptor radionuclide therapy upfront, according to Chauhan.

In asymptomatic patients with slow-growing tumors or low-bulk metastatic disease, Chauhan recommends somatostatin analogs and potentially a mTOR inhibitor afterwards before the patient is exposed to radionuclide therapy. Chauhan continues to search for conclusive data to guide sequencing decisions for patients with GEP-NETs.

Aman Chauhan, MD, discusses sequencing decisions when treating patients with gastroenteropancreatic neuroendocrine tumors.

Dr. Chauhan on Sequencing Therapies for GEP-NETs

Aman Chauhan, MD, a medical oncologist at University of Kentucky, discusses the role of somatostatin analogs in treating patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

Somatostatin analogs form the backbone of treatment for patients with GEP-NETs and changed the way these are managed, explains Chauhan. Somatostatin analogs are often used for frontline treatment of patients with GEP-NETs and work well for those with functional and nonfunctional NETs, evident through the randomized CLARINET study, says Chauhan. This phase III study examined lanreotide (Somatuline Depot) versus placebo in patients with metastatic GEP-NETs.

In addition to being effective in treating patients with GEP-NETs, somatostatin analogs are well tolerated with a better safety profile than traditional chemotherapy, targeted therapy, or radiation-based therapy, concludes Chauhan.

Aman Chauhan, MD, discusses the role of somatostatin analogs in treating patients with gastroenteropancreatic neuroendocrine tumors.

Aman Chauhan, MD

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