Research-informed answers to your most important questions about neuroendocrine cancer.
By Anna C. Greene, PhD, Chief Scientific Officer, Neuroendocrine Tumor Research Foundation (NETRF)
You asked. We’re answering.
Through the 2026 Know Your NETs survey, patients and caregivers told us what they most want to understand about neuroendocrine cancer: why diagnosis still takes so long, what new treatments are coming, what happens after PRRT, why some NET subtypes receive less research attention, what genetics can and cannot explain, why a cure has not yet been found, and how people can live well with this disease. The questions were practical, urgent, and deeply informed by lived experience.
This post is the first in You Ask, NETRF Answers, a new series offering research-informed responses to the questions patients and caregivers ask most often. In each post, we will answer as clearly as we can based on what is known today, what current research suggests, and where uncertainty remains. When the field does not yet have a good answer, we will say so.
These posts are educational, not medical advice, and they are not a substitute for guidance from your care team.
A note on scope:
This post focuses primarily on well-differentiated neuroendocrine tumors, or NETs. Poorly differentiated neuroendocrine carcinomas (NECs) are biologically distinct, often behave more aggressively, and frequently follow a different diagnostic path. NECs raise separate and important questions that we will address in a future post.
Why does it still take so long to diagnose a NET?
For many patients, the answer involves biology, medical training, health system structure, and access to specialized imaging. It also involves something simpler and harder: NET symptoms often look exactly like more common conditions.
The fact that diagnosis is difficult does not make delay acceptable. Patients should not have to spend years being told their symptoms are “just IBS,” “just anxiety,” or “probably nothing” before someone considers a neuroendocrine tumor.
Why are NETs so hard to diagnose?
NETs are not one disease. They can arise in many locations, including the small intestine, pancreas, rectum, stomach, appendix, and lung. Some grow slowly for years. Others are more aggressive. Some produce hormones that cause noticeable symptoms. Others do not. That biological diversity makes NETs difficult to recognize, particularly outside specialized centers.
Early symptoms also overlap with much more common conditions. Diarrhea, abdominal pain, bloating, flushing, reflux, wheezing, and fatigue have many causes. A primary care physician or gastroenterologist may see hundreds of patients with irritable bowel syndrome, reflux disease, gallbladder problems, asthma, food intolerance, or anxiety before encountering one patient with a NET.
Not all NETs cause carcinoid syndrome. Not every patient experiences flushing or diarrhea. Many patients have vague or intermittent symptoms, unremarkable routine bloodwork, or tumors that are small and difficult to visualize on standard imaging.
Even when a clinician does suspect a NET, the right tests may not be readily available in every community. Specialized imaging, expert pathology review, and access to NET-experienced centers remain unevenly distributed, particularly outside academic medical centers.
What has research improved?
Research has already changed NET diagnosis in meaningful ways.
One of the most significant advances is somatostatin receptor imaging. Many NETs express somatostatin receptors on their surface. Gallium-68 DOTATATE PET/CT uses this biology to detect disease with considerably greater sensitivity than conventional imaging approaches, and also provides information relevant to treatment eligibility, including suitability for peptide receptor radionuclide therapy (PRRT). Related agents, such as Gallium-68 DOTATOC, have shown similar value across different settings.
Somatostatin receptor imaging is a genuine advance. But a scan can only help once a clinician orders it. Many patients experience delays earlier in the diagnostic pathway, before anyone has considered a NET.
Research has also expanded our understanding of biomarkers. Some NETs release hormones or their breakdown products that can be measured in blood or urine. For example, urinary 5-HIAA (5-hydroxyindoleacetic acid) can help evaluate serotonin-producing tumors associated with carcinoid syndrome. Other tests are selected based on the suspected tumor type and the patient’s symptoms.
Chromogranin A, or CgA, has historically been used as a general NET marker, but it has important limits. It can be elevated for reasons unrelated to NETs, including proton pump inhibitor use, kidney disease, and cardiac disease. It can also be normal in some patients with confirmed NETs, especially smaller or non-secreting tumors. Because of these limitations, CgA is not a reliable early detection test, and a normal result does not rule out a NET.
Newer multigene blood tests are being studied to detect or monitor NET disease, with some showing promise in research settings. Important questions remain about which patients benefit most, how results should influence treatment decisions, and when these tests should be used in clinical practice. None currently replaces careful clinical evaluation, imaging, pathology review, and specialist interpretation.
Why can tests miss NETs?
Many patients did seek care. Many had testing. So why was the NET still missed?
Location is often part of the answer. A standard colonoscopy examines the colon and may reach the terminal end of the small intestine, but it does not visualize the full small intestine. Small intestinal NETs can therefore be present but outside the field of view. These tumors may also be small, multifocal (occurring at multiple sites), or difficult to identify without specialized imaging.
Similar challenges arise elsewhere. Pancreatic NETs are frequently nonfunctional, meaning they may not produce a hormone syndrome that causes obvious symptoms. They are often identified incidentally on imaging done for another reason, or after the tumor has grown or spread. Lung NETs can resemble more common respiratory diagnoses, including asthma, chronic bronchitis, COPD, or recurrent pneumonia.
In some patients, the first clear sign of disease is not the primary tumor itself, but spread to the liver or lymph nodes detected on imaging. Even after thorough evaluation, the site of the original tumor may remain unknown. Among patients presenting with metastatic NETs, a meaningful proportion have no identifiable primary site identified on initial workup, though definitions and rates vary across studies and settings.
Pathology is also part of the diagnostic picture. A correct diagnosis depends on obtaining adequate tissue, applying the right staining panels, and interpreting findings with expertise in NET pathology. Tumor grade, differentiation, Ki-67 proliferation index, mitotic rate, and the site of origin all carry clinical significance because they affect prognosis and determine which treatments are appropriate.
This is why expert review matters. A consultation at a NET-experienced center can change the interpretation of imaging, pathology, staging, or treatment options, even for patients who receive most of their care closer to home.
What don’t we know yet?
We do not currently have a simple, reliable test that can detect NETs early in the general population. Neuroendocrine cancers are uncommon and biologically diverse, which makes broad early detection difficult to design and validate. Recent U.S. registry data estimate about 8.5 new neuroendocrine cancer diagnoses per 100,000 people each year, or less than 0.01% of the population annually. Spread across the U.S. physician workforce, that averages to roughly one new diagnosis per direct patient care physician every 30 years. In reality, cases are not evenly distributed, but the scale helps explain why many front-line clinicians rarely encounter these cancers and why better tools, greater awareness, and clearer diagnostic pathways are so important.
We also do not fully understand why most sporadic NETs develop. Some hereditary syndromes, including MEN1, VHL, and others, substantially increase NET risk and warrant surveillance in affected families. But most NETs are not clearly inherited. For many patients, NET development is complex, involving inherited and acquired genetic changes, chance, and other influences that researchers may not yet understand.
Finally, we do not yet know the most effective way to help frontline clinicians identify NETs earlier without triggering excessive testing for every patient whose symptoms happen to overlap with NET presentation. The goal is to identify patterns, combinations of symptoms, and “red flag” features that should prompt earlier consideration of a NET, without creating a situation in which routine symptom complaints lead to unnecessary and costly workups. Artificial intelligence may eventually help by recognizing patterns across symptoms, labs, imaging, pathology, family history, and clinical history, but these tools will need careful validation to ensure they guide the right patients toward the right follow-up.
What could help close the diagnosis gap?
Closing the gap will require awareness and research working together. Awareness gives more clinicians the tools to recognize when NETs should be considered. Research creates better tools, clearer pathways, and stronger evidence for what to do next.
Earlier detection is one of the pillars of NETRF’s Research Roadmap, alongside new therapies and precision medicine. When NETs are identified before they have spread, surgical resection may be curative for a subset of patients, which means the stakes of earlier detection are high.
NETRF’s priorities in this area are not focused on broad population screening. They focus on situations where earlier answers could realistically change care: patients with suspicious combinations of symptoms or concerning imaging findings, individuals with hereditary NET risk syndromes, people with recognized precursor conditions such as DIPNECH (diffuse idiopathic pulmonary neuroendocrine cell hyperplasia), and patients in post-treatment monitoring for recurrence or disease progression.
Several lines of research could contribute. Liquid biopsy approaches, including methylation-based blood tests and multi-analyte circulating biomarker panels, are under active investigation as ways to detect or monitor neuroendocrine disease. Advances in CT and PET imaging, combined with computational tools including AI-assisted image analysis, are being explored to improve detection and characterization of small or anatomically challenging tumors. And research integrating symptom patterns, laboratory values, imaging findings, pathology, family history, and tumor biology may help identify which patients warrant faster or more targeted evaluation.
Patient-informed research is essential to getting this right. Patients know where delays occur because they have lived through them. Bringing that knowledge into research design helps ensure that new tools and care pathways address the problems patients actually face.
What can patients do now?
Many readers may already have a NET diagnosis. If that is true for you, this information may still help you understand why the path to diagnosis was so difficult, what questions to ask now, and how your experience can help improve care for others.
If you are still seeking answers, or if symptoms are changing, persistent, or not fully explained, it is reasonable to ask your physician directly: “Could these symptoms fit with a NET, and what would help rule that in or out?”
For those already diagnosed, a symptom log can still be useful. Record what happens, how often, what seems to trigger it, how long it lasts, and whether it occurs alongside other symptoms or changes in how you feel. This can help your care team understand patterns over time.
It may also be worth asking whether your case has been reviewed by a NET-experienced team, especially if your diagnosis was recent, your primary site is uncertain, your symptoms are changing or difficult to manage, or your treatment plan is unclear. A second opinion does not mean starting over. It can help confirm the diagnosis, review imaging and pathology, and clarify options.
The bottom line
NETs are hard to diagnose because they are rare, biologically diverse, and often mimic much more common conditions. But long diagnostic delays are not inevitable, and they are not acceptable.
Research has already improved the field, most visibly through somatostatin receptor imaging and a deeper understanding of NET biology. But significant gaps remain. Better early detection tools, clearer diagnostic pathways, more equitable access to specialized imaging, broader clinician education, and stronger systems for connecting patients to NET expertise all remain important areas of need.
The patients who responded to the Know Your NETs survey made something clear: the diagnostic journey is not just the beginning of the story. For many, it is one of the hardest parts of the story, and it deserves serious research attention.
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Questions or feedback?
If this post raised questions you would like to see addressed in a future installment of this series, you can reach us at info@netrf.org.