By Anna Greene, PhD, NETRF Director of Research
We’re excited to share insights from a new ENETS (European Neuroendocrine Tumor Society) position statement, published in the Journal of Neuroendocrinology, addressing a complex and important topic: the treatment of Grade 3 well-differentiated neuroendocrine tumors (NET G3) of the gastroenteropancreatic tract.
What Are NET G3 Tumors?
Neuroendocrine tumors can occur in the pancreas, intestines, lungs, and other parts of the body. They’re graded based on how fast they grow:
- G1 and G2 NETs grow more slowly and often have better outcomes.
- G3 NETs are faster-growing and more unpredictable.
This makes NET G3 especially challenging—patients often face tough choices about treatment, and doctors have had limited evidence to guide them. That’s why this new expert consensus is so important.
Key Takeaways for Patients & Families
The ENETS experts carefully reviewed all available evidence and shared recommendations on some of the most pressing questions. Here’s what they concluded:
- Localized tumors (still contained): If the tumor can be removed, surgery offers the best chance for long-term control. Sometimes doctors may give treatment first (chemo or a special targeted radiation called PRRT) to shrink a tumor that’s harder to remove. Extra treatment after surgery is not routine, but may be considered for higher-risk cases.
- When the cancer has spread to a few spots (“oligometastatic”): In carefully chosen patients, surgery or focused local treatments (like heating tumors, blocking their blood supply, or pinpoint radiation) can sometimes help keep the disease under control for longer.
- Advanced disease (widespread):
- PRRT is now a first-line option for patients whose tumors are somatostatin receptor positive.
- Chemotherapy (CAPTEM or FOLFOX) also works well and is widely used.
- Doctors usually avoid older chemo drugs (platinum/etoposide) unless the cancer is very aggressive.
- If the first treatment stops working, patients usually switch to the other option (chemo ↔ PRRT).
- Immunotherapy (checkpoint inhibitors): These medicines are not effective for most NET G3 patients, unless the tumor has certain rare genetic features. For now, they are mainly available in clinical trials.
- Targeted therapy: Drugs like everolimus, sunitinib, and cabozantinib may help after other treatments, but research is still early.
- Re-biopsy: NET G3 tumors can change over time. A new biopsy can show whether the tumor is behaving differently and help guide the next treatment choice.
- NET G3 outside the digestive tract (like in the lung): These may behave differently, but for now are often treated in a similar way. Being seen at a specialist NET center is key.
Why This Matters
For patients and families, this consensus offers much-needed clarity in a gray area of NET care. For doctors, it provides expert-backed guidance where research is still limited. And for researchers and funders like NETRF, it highlights urgent gaps—especially the need for more clinical trials, better imaging tools, and more precise ways to match treatment to each tumor.
A Message of Hope
Grade 3 NETs have long been a difficult puzzle, but thanks to global collaboration and growing research momentum, the path forward is becoming clearer. Together, with patients, caregivers, doctors, and researchers, we are moving toward better treatments and brighter outcomes.
For more on NET G3, consult our NET Knowledge Center and listen to our NETWise podcast episode on high-grade NETs and NECs.