By Anna C. Greene, PhD, NETRF Chief Scientific Officer
When someone is diagnosed with metastatic neuroendocrine cancer, one of the most confusing questions can be: Why would doctors still talk about surgery if the cancer has already spread?
For many cancers, surgery is often thought of as a treatment used when all visible disease can be removed. But neuroendocrine tumors (NETs), can behave differently. Many people live with metastatic disease for years, and treatment decisions often focus not only on removing cancer, but also on preventing complications, controlling symptoms, and preserving quality of life.
This question can arise across different types of NETs, but this article focuses mainly on small-intestinal NETs, where the role of removing the original tumor in the setting of metastatic disease has been especially debated.
Two recent scientific papers help explain why this question remains unsettled. One is an Emory/Cedars-Sinai review that summarizes the existing evidence on primary tumor removal in metastatic small-intestinal NETs and highlights the need for more patient-centered research. The other is an ENETS position statement that offers expert guidance on when surgery of the primary tumor should be considered in metastatic small-intestinal and pancreatic NETs.
When surgery may still prove effective in metastatic small-intestinal NETs
Small-intestinal NETs often spread before they are diagnosed. In population-based studies, at least 35% of patients present with metastatic disease at diagnosis, and some studies report metastatic rates as high as 60%. Symptoms can be vague, including abdominal pain, intermittent obstructive symptoms, or bleeding, which can contribute to delayed diagnosis.
Even when the disease has spread, the original tumor and nearby mesenteric lymph nodes can still cause problems. Small-intestinal NETs may be associated with fibrosis, or scar-like tissue, in the mesentery, the fold of tissue that attaches the intestines to the abdominal wall. This can lead to bowel obstruction, reduced blood flow to the intestine, pain, or other serious complications. For this reason, surgery may be considered not only as a cancer-directed treatment, but also as a way to prevent or manage local complications.
Importantly, some people may not realize that intermittent abdominal pain, changes in bowel habits, or vague digestive symptoms could be related to the primary tumor or mesenteric disease. In this setting, “asymptomatic” does not necessarily mean the tumor is truly silent.
Experts generally agree that surgery is appropriate when the original tumor is causing serious problems, such as bowel blockage, reduced blood flow to the intestine, or bleeding. The harder question is what to do when the cancer has already spread, all disease cannot be removed, and the primary tumor does not appear to be causing symptoms. Both the Emory/Cedars-Sinai review and the ENETS position statement emphasize that this decision should be individualized and reviewed by a multidisciplinary NET team, including surgical expertise. The Emory/Cedars-Sinai review also notes that some patients who appear “asymptomatic” may have subtle or unrecognized symptoms, and that primary tumor removal may help prevent future complications in selected patients. At the same time, the evidence is not definitive, and the risks and possible benefits of surgery need to be weighed carefully for each person.
What the evidence suggests
Several retrospective studies suggest that people with metastatic small-intestinal NETs who had their primary tumor removed lived longer than those who did not. Some studies also suggest that upfront surgery may reduce unplanned hospital admissions and the need for later bowel-related surgery. This distinction is important because many people with metastatic small-intestinal NETs live for many years, leaving time for the primary tumor or mesenteric disease to cause future complications.
But these studies are difficult to interpret. They were not randomized trials. Patients selected for surgery may have been younger, healthier, had lower-risk tumors, or had less complex metastatic disease. When researchers try to adjust for these differences, the apparent survival benefit sometimes becomes smaller or disappears.
That does not mean surgery is unimportant. It means the key question is not simply “Does surgery help?” The better question is, “Which patients are most likely to benefit, what risks would surgery involve, and what outcomes matter most to the individual patient?”
Survival is not the only desired outcome
For people living with metastatic small-intestinal NETs, overall survival may not be the only, or even the most useful, measure of benefit. Many patients live with the disease for a long time. During that time, avoiding urgent complications, reducing hospitalizations, limiting the need for emergency procedures, and maintaining quality of life are deeply important.
The Emory/Cedars-Sinai review emphasizes the need for future studies that include outcomes such as quality of life, unplanned hospital admissions, obstruction-free survival, and cumulative surgical burden, not just survival alone.
This is an important point for NETRF. Research in neuroendocrine cancer should reflect the real decisions patients face, including how treatments affect daily life, future risk, and the ability to live well with a chronic cancer.
What patients can ask their care team
For patients with metastatic small-intestinal NETs, surgery decisions are highly individual. The right answer depends on tumor location, symptoms, tumor biology, extent of metastatic disease, overall health, surgical risk, and patient goals. Patients may want to ask:
- Is my primary tumor causing symptoms now, including symptoms I may not have connected to the tumor?
- Is there a risk of bowel obstruction, bleeding, or reduced blood flow to the intestine?
- Do I have mesenteric disease or fibrosis that could cause future problems?
- Would surgery change my overall treatment plan, including the timing of somatostatin analogues, PRRT, liver-directed therapy, targeted therapy, or another treatment?
- What are the risks of surgery in my specific situation?
- What could happen if we monitor rather than operate now?
- Has my case been reviewed by a multidisciplinary NET team that includes surgical expertise?
NETRF’s perspective
At NETRF, we see this debate as a clear example of why neuroendocrine cancer research must be both scientifically rigorous and patient-centered. Small-intestinal NETs can behave very differently from many other cancers. Even when metastatic disease cannot be fully removed, the primary tumor and nearby mesenteric disease may still affect symptoms, future risk, and quality of life.
The current evidence supports a thoughtful, individualized approach. For some patients with metastatic small-intestinal NETs, removing the primary tumor may help prevent future complications. For others, the risks of surgery may outweigh the likely benefit, and systemic therapy, liver-directed therapy, PRRT, active surveillance, or another approach may be more appropriate.
The broader lesson applies across NET care: complex treatment decisions should not be made in isolation. Patients should have access to a multidisciplinary NET team, including surgical expertise, medical oncology, radiology, nuclear medicine when relevant, and other specialists who understand the long-term course of neuroendocrine cancer.
The importance of a personalized approach
If neuroendocrine cancer has spread, surgery may still be discussed for several reasons: to treat symptoms, reduce the risk of future complications, remove disease that can safely be removed, or support a broader treatment plan. In metastatic small-intestinal NETs, both the Emory/Cedars-Sinai review and the ENETS position statement support careful, individualized consideration of primary tumor removal, even when symptoms are not obvious. However, the evidence is still incomplete, and the decision must be weighed carefully for each patient.
The key takeaway for patients is that the question deserves careful review by a multidisciplinary NET team, with attention to symptoms, tumor biology, extent of disease, surgical risk, treatment goals, and quality of life.
Supporting science that drives better outcomes
At NETRF, we know that decisions like this can feel overwhelming for patients and families. Our goal is to support the research needed to make those decisions clearer, more personalized, and more grounded in the outcomes that matter to patients, including quality of life, symptom control, and avoiding serious complications. Better evidence can help patients and their care teams choose the right approach at the right time.
_______________________________________________________________________________________________________________
Learn more: Explore NETRF’s resources on surgery for neuroendocrine tumors and listen to the NETWise podcast episodes on small bowel NETs or surgery and interventional radiology for NETs.