Fact Sheets
Grading & Staging
Understanding the grade and stage of neuroendocrine cancer is crucial in guiding management and developing a treatment plan.
Grading is the description a pathologist gives to neuroendocrine cancer cells when they are viewed under a microscope. The pathologist looks at both the structure of the cell in comparison to a normal cell, and also the growth rate of the neuroendocrine cancer cell.
Staging describes whether the disease is confined to its original site or if it has spread to lymph nodes or other organs of the body.
Grading
Grading for neuroendocrine cancers are based on a variety of factors:
- How slowly or quickly cells are growing and dividing (using both the Ki-67 proliferation index and the mitotic rate)
- Whether the cancer cells are well differentiated (cancer cells that look similar to normal cells)
- Whether the cancer cells are poorly differentiated (cancer cells that look very different to normal cells)
Understanding tumour grade is one of the most important parts of diagnosing neuroendocrine cancer. Grade describes how fast a tumour is growing and how abnormal the cancer cells look under a microscope. Alongside stage, tumour location, and symptoms, grading helps your healthcare team choose the most appropriate treatment plan.
Neuroendocrine cancers are grouped into three grades, from slow growing to more aggressive. These grades are based on measurements such as the Ki-67 index, mitotic count, and differentiation. While grading provides valuable guidance, every person’s situation is unique, and treatment decisions are always tailored to the individual.
Grading of Neuroendocrine Cancers (NETs)
Grading of Neuroendocrine Carcinomas (NECs)
Staging
Classifying neuroendocrine cancer into one of the 4 stages is site-specific and should be in the form of the tumour, nodes and metastases (TNM) system ( refer to the 8th edition of the American Joint Committee).
T (Tumour)
Describes how deeply the tumour has grown into the surrounding tissue. A higher number (1 to 4) means it has invaded more deeply.
N (Nodes)
Shows whether nearby lymph nodes contain cancer cells. Numbers range from 0 to 3, indicating the extent of lymph node involvement.
M (Metastasis)
Indicates if the cancer has travelled to distant parts of the body. M0 means no evidence of spread whereas M1 means the cancer has spread to other organs.
Once the T, N, and M values are identified, they are then combined to determine the overall stage, ranging from 1 to 4.
Stage 1
Cancer small, is localised and hasn’t spread to lymph nodes
Stage 2
Cancer has grown into nearby tissue but not into the lymph nodes.
Stage 3
Cancer has spread to the lymph nodes but not to distant parts of the body
Stage 4
The cancer has spread to distant organs or other body parts – this is called metastatic disease.
Frequently asked questions about neuroendocrine cancer grades
Grade describes how quickly a neuroendocrine tumour is growing and how aggressive it appears under a microscope. It helps your healthcare team understand how the cancer may behave and which treatments are most appropriate.
Doctors use two main markers. The Ki-67 index measures how many tumour cells are actively dividing, and the mitotic rate counts how many cells are seen dividing under a microscope. Together, these help determine whether a tumour is Grade 1, Grade 2, or Grade 3.
Grade 1 tumours usually grow slowly and are well differentiated. Grade 2 tumours grow at a moderate rate. Grade 3 tumours grow more quickly and may be either well differentiated neuroendocrine cancer (NET) G3 or poorly differentiated neuroendocrine carcinomas (NECs).
Higher grade tumours often grow faster and may require more intensive treatment. However, every person’s situation is different, and outcomes depend on many factors including stage, tumour location, and response to therapy.
No. Grade describes how aggressive the tumour cells look, while stage describes how far the cancer has spread in the body. Both are important when planning treatment.
In some cases, the tumour biology may change. Doctors may repeat biopsies or imaging if the disease behaves differently, to ensure treatment decisions remain accurate.
The Ki-67 index refers to a key biomarker that shows how fast tumour cells are growing. A low Ki-67 suggests slower growth, while a higher number indicates more rapid cell division and often different treatment approaches.
Yes. Lower grade tumours may be managed with surgery, monitoring, or treatments like somatostatin analogues, while higher grade tumours may require chemotherapy or more intensive therapies.
A specialist pathologist reviews biopsy or surgical samples to assess the tumour. Your multidisciplinary NET team then uses this information to guide treatment planning.
NeuroEndocrine Cancer Australia provides education resources, assistance finding NET Specialists, and access to the NET Nurse service to help people living with NETs and their families understand grading, treatment options, and next steps.
Next steps
It’s important to note that treatment decisions are made on an individual basis, considering factors such as the tumour’s grade, stage, location, overall health and any other existing health conditions.
A multidisciplinary team will collaborate to develop a comprehensive treatment plan that balances the goal of targeting the cancer while preserving your quality of life.
If you or someone you know is dealing with a neuroendocrine cancer, consulting with medical professionals who specialise in this area will provide the most accurate and personalised guidance.
Helpful Resources
Booklets & Guides
Acronyms & Terminology for Neuroendocrine Cancer Patients
Grading & Staging
Factors Influencing Prognosis in Neuroendocrine Tumours
Grading & Staging
Gastroenteropancreatic NET Grading: Variations and Implications
Grading & Staging
Grading of Pulmonary Neuroendocrine Tumours
Grading & Staging
Ki-67 Proliferation Index in NET Grading
Educational Videos
NETs Under the Microscope – Webinar
Grading & Staging
Neuroendocrine Cancer Biomarkers
Courses
Neuroendocrine Tumour Education Course
Booklets & Guides
