The first 60 days: Grade 3 well-differentiated neuroendocrine tumour
Grade 3 well-differentiated neuroendocrine tumours divide fast enough to be called grade 3 yet still look and behave like their slower relatives rather than like neuroendocrine carcinoma. Recognised as separate since 2017, they keep the somatostatin receptor, respond less well to platinum chemotherapy, and in the NETTER-2 trial were among the first treated with lutetium-177 dotatate up front. Below, week by week, is what OnCo's record of Grade 3 well-differentiated neuroendocrine tumour says about the first two months: the order is typical, the timing is yours to ask about. Sections appear only where the record has something to say. Orientation, not medical advice.
What happens now
Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.
Morphology, Ki-67 and p53 or Rb immunohistochemistry to separate grade 3 tumour from carcinoma; somatostatin receptor and FDG PET together.
Ask which of these were tested and what the results were; see the report reader for what each value means.
These specialties appear in the standard of care for this cancer. In most centres they meet weekly as a tumour board to agree each plan; you can ask when yours was discussed and what was decided.
- PathologistNamed in the standard of care for: Advanced, somatostatin receptor-positive.
- RadiologistNamed in the standard of care for: Diagnosis.
- SurgeonNamed in the standard of care for: Limited disease.
- Medical oncologistNamed in the standard of care for: Advanced, somatostatin receptor-positive, Advanced, shrinkage needed or receptor-negative, Trials, Limited disease.
- Clinical oncologist (radiotherapy)Named in the standard of care for: Advanced, somatostatin receptor-positive, Trials.
A second opinion from a centre that treats many similar cases is normal, not rude; the standard of care tells you what to compare it against.
Each row is a setting from the standard of care, in the order it usually arises. Not all will apply to you; your stage and biomarkers decide which do. The guideline grade, where recorded, says how strong the evidence is.
Resection and liver-directed therapy as for other well-differentiated tumours.
Lutetium-177 dotatate first line for Ki-67 up to 55 percent (NETTER-2); somatostatin analogue alongside.
Capecitabine with temozolomide; everolimus or sunitinib for pancreatic tumours; platinum-etoposide for carcinoma-like tempo or Ki-67 near 55 percent.
COMPOSE: 177Lu-edotreotide against CAPTEM, everolimus or FOLFOX in aggressive grade 2 and grade 3 gastroenteropancreatic tumours.
Generated from this cancer's standard of care, biomarkers and open problems. Take the group that matches where you are. To tick, add your own and print, open the one-page appointment sheet.
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example Ki-67 above 20 percentwith well-differentiated morphology, Retained p53 and Rb by immunohistochemistry, Somatostatin receptor PET, usually positive, with FDG PET for dual-tracer assessment, Chromogranin A, MEN1, DAXX and ATRX alterations), and what were the results?These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Recognised subtypes for this cancer include Grade 3 well-differentiated pancreatic NET, Grade 3 well-differentiated small intestinal and other gastroenteropancreatic NET, NET G3 with Ki-67 20 to 55 percent, somatostatin receptor-positive.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
Diagnosis
- For my situation (diagnosis), which of the standard options do you recommend and why?Guideline options include: Morphology, Ki-67 and p53 or Rb immunohistochemistry to separate grade 3 tumour from carcinoma; somatostatin receptor and FDG PET together.
Advanced, somatostatin receptor-positive
- For my situation (advanced, somatostatin receptor-positive), which of the standard options do you recommend and why?Guideline options include: Lutetium-177 dotatate first line for Ki-67 up to 55 percent (NETTER-2); somatostatin analogue alongside.
- Am I a candidate for Lutetium-177 dotatate, Somatostatin analogues (octreotide, lanreotide), and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of Study to Evaluate the Efficacy and Safety of Lutathera in Patients With Grade 2 and Grade 3 Advanced GEP-NET apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Advanced, shrinkage needed or receptor-negative
- For my situation (advanced, shrinkage needed or receptor-negative), which of the standard options do you recommend and why?Guideline options include: Capecitabine with temozolomide; everolimus or sunitinib for pancreatic tumours; platinum-etoposide for carcinoma-like tempo or Ki-67 near 55 percent.
- Am I a candidate for Capecitabine + temozolomide (CAPTEM), Everolimus, Sunitinib or related drugs, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Trials
- For my situation (trials), which of the standard options do you recommend and why?Guideline options include: COMPOSE: 177Lu-edotreotide against CAPTEM, everolimus or FOLFOX in aggressive grade 2 and grade 3 gastroenteropancreatic tumours.
- Am I a candidate for 177Lu-edotreotide, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of Lutetium 177Lu-Edotreotide Versus Best Standard of Care in Well-differentiated Aggressive Grade-2 and Grade-3 GastroEnteroPancreatic NeuroEndocrine Tumors (GEP-NETs) - COMPOSE apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Limited disease
- For my situation (limited disease), which of the standard options do you recommend and why?Guideline options include: Resection and liver-directed therapy as for other well-differentiated tumours.
Any stage
- Are there clinical trials I could join, for example of Lutetium 177Lu-Edotreotide Versus Best Standard of Care in Well-differentiated Aggressive Grade-2 and Grade-3 GastroEnteroPancreatic NeuroEndocrine Tumors (GEP-NETs) - COMPOSE, 177Lu-edotreotide, Lutetium-177 dotatate, Capecitabine + temozolomide (CAPTEM)?Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Supportive care improves quality of life and helps patients complete treatment.
- I read that “The Ki-67 boundary between grade 3 tumour and carcinoma is not sharp, and some cases can only be settled by molecular testing”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “No trial has been run in grade 3 tumours alone; NETTER-2 and COMPOSE mix them with grade 2”. How does that affect my plan?Open problems are where trials and second opinions matter most.
Trials open now for this cancer in OnCo, largest phase first. Joining a trial is a decision like any other: ask what the comparison arm is, whether a placebo is used, and what happens if you leave. The cancer page searches ClinicalTrials.gov live for more.
- Lutetium 177Lu-Edotreotide Versus Best Standard of Care in Well-differentiated Aggressive Grade-2 and Grade-3 GastroEnteroPancreatic NeuroEndocrine Tumors (GEP-NETs) - COMPOSEPhase 3 · active · NCT04919226A Prospective, Randomised, Controlled, Open-label, Multicentre Study to Evaluate Efficacy, Safety and Patient-Reported Outcomes of Peptide Receptor Radionuclide Therapy (PRRT) With 177Lu-Edotreotide Compared to Best Standard of Care in Patients With Well-differentiated Aggressive Grade 2 and Grade 3, Somatostatin Receptor-Positive (SSTR+), Neuroendocrine Tumours of GastroEnteric or Pancreatic Origin
- Study to Evaluate the Efficacy and Safety of Lutathera in Patients With Grade 2 and Grade 3 Advanced GEP-NETPhase 3 · active · NCT03972488A Phase III Multi-center, Randomized, Open-label Study to Evaluate the Efficacy and Safety of Lutathera in Patients With Grade 2 and Grade 3 Advanced GEP-NET
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- Grade 3 well-differentiated neuroendocrine tumour: the full pageGrade 3 well-differentiated neuroendocrine tumours divide fast enough to be called grade 3 yet still look and behave like their slower relatives rather than like neuroendocrine carcinoma. Recognised as separate since 2017, they keep the somatostatin receptor, respond less well to platinum chemotherapy, and in the NETTER-2 trial were among the first treated with lutetium-177 dotatate up front.
- One-page appointment sheetYour questions, the words you may hear, what to bring, and space for the answers. Print it.
- Treatment sequencingWhich treatment tends to follow which, line by line.
- NavigatorStandard of care for your stage, what you have tried, and trials near you.
- PRRT (peptide receptor radionuclide therapy): A radioactive drug for neuroendocrine tumours: a small peptide that homes to the somatostatin receptor on the tumour cells carries lutetium-177, which irradiates them from within.
- Tumour differentiation (well / moderately / poorly differentiated): How much the cancer cells still resemble the normal tissue they came from.
- Chromogranin A: Chromogranin A is a protein released by neuroendocrine cells and measured in blood to follow tumour burden; it is unreliable because acid-reducing drugs and kidney disease also raise it.
- Neuroendocrine tumour grade (Ki-67) and WHO classification: How fast the tumour cells are dividing, measured by Ki-67 staining, separates slow-growing neuroendocrine tumours from aggressive neuroendocrine carcinomas and decides the treatment.
- Liver-directed therapy (TACE, TARE, HAI, ablation): The set of treatments aimed only at tumours in the liver, delivered through its artery or by needle, used when the liver is the main or only site of disease: chemoembolisation, radioactive beads, ablation and infusion pumps.
- Hepatectomy (liver resection): Cutting out the part of the liver containing tumour.
Every term links to the glossary.