Understanding the Diagnosis and Prognosis of Neuroendocrine Tumors

Diane Reidy-Lagunes, MD: Neuroendocrine cancers are a little bit tricky because they’re uncommon cancers, though not as rare as people think. There are probably about 8000 to 10,000 patients a year, but what’s challenging about them is they’re quite heterogeneous. What I mean by that is there are certain classifications that we need to understand when we’re seeing a patient faced with neuroendocrine cancers, so that we could better understand the type of cancer and then ultimately the types of treatments that we’re going to offer. The first thing is where the cancer starts. These are diseases that can start anywhere in the body. The most common location is somewhere in the GI [gastrointestinal] tract or in the lung, but again it can also develop in the GYN [gynecologic] as well as GU [genitourinary] systems. Where the cancer starts is very important. The second thing we look at is what the cancer looks like under the microscope. The grade of the cancer can also help us further classify the disease, understand how aggressive could it potentially behave, and how aggressive we want to be in the types of treatments that we’re offering. The primary site of origin, the grade of the tumor, and then the third thing is the burden of disease. How much cancer that patient may have can also help us better understand and classify how we’re going to treat it.

For the diagnosis of neuroendocrine cancers, it really demands a multidisciplinary approach. The most important member of that team is the pathologist because what they look and confirm for neuroendocrine cancer is obviously critically important. The pathologist will give us 2 pieces of information. The first thing they do is they look at the cells and tell us what the architecture of those cells look like. Are they well differentiated or poorly differentiated? Treatments vary depending on if it’s well differentiated or poorly differentiated. The second thing that they tell us is the grade of the tumor, and that’s based on the WHO [World Health Organization] classification where we have grades 1, 2, and 3, grade 1 being low grade, grade 2 being intermediate grade, and grade 3 being high grade. That’s very important for us in terms of our pathology diagnosis. We also have other team members that can help us. Our gastroenterologist will also help us often find the primary, which is very often in the small bowel but also in other locations, and then we have the medical oncologist as well as surgeons to help us define the treatment options.

When we find the classifications and the pathology of NETs [neuroendocrine tumors], they can be very helpful for us to understand prognosis and treatment recommendations that we’re going to have. We know that the grading is the most important prognostic feature that we have in neuroendocrine cancer, so we can’t trump the biology. Biology is the most important piece of information that we have, and the best way that we have today, in 2021, is to define that by grade. Tumors that are low grade, which is a Ki-67 [index] less than 3%, tend to portend the best prognosis. Intermediate-grade cancers, which are Ki-67 between 3% and 20%, tend to behave like low grade potentially, and sometimes unfortunately more like high grade. Then those high-grade tumors, which are Ki-67 greater than 20%, are the tumors that we worry about the most because they can portend a more aggressive course.

Transcript Edited for Clarity