Understanding the Diagnosis and Treatment of Neuroendocrine Tumors

Dr. Pamela L. Kunz, professor of Internal Medicine (Medical Oncology) and director of the Center for Gastrointestinal Cancers at Smilow Cancer Hospital and Yale Cancer Center, where she also serves as chief of GI Medical Oncology, sat down with CURE to discuss Neuroendocrine Tumors (NETs) Awareness Month.

In this interview, Kunz explains what NETs are, how they differ from more common cancers, and the challenges in diagnosing and treating them. She also highlights the importance of patient education, awareness initiatives and advocacy, sharing key resources and strategies to help patients and caregivers navigate this complex and increasingly prevalent disease.

CURE: What are these neuroendocrine tumors, and how do they differ from more common types of cancers?

Kunz: Neuroendocrine tumors are different from other cancer types because they can originate in almost any part of the body. They arise from neuroendocrine cells that are scattered throughout the body. Most commonly, they originate in the small intestine, the lungs and the pancreas.

Neuroendocrine tumors, or NETs, are categorized in a few different ways. One key area is by grade, which refers to whether they are slower-growing or faster-growing. A key difference compared with other solid tumors is that the large majority of NETs tend to be slower-growing, so they progress more slowly than adenocarcinomas, which are the more common cancer type in the GI tract and lungs.

Are there any early symptoms or warning signs patients should be aware of when regarding NETs?

Early warning signs for NETs can be challenging, just because they may differ depending on where the cancer originates. If a cancer originates in the lungs, patients may have a cough or shortness of breath. If a neuroendocrine tumor originates in the GI tract, they may have abdominal pain or other GI symptoms. Again, because many of these tend to be slower-growing, they can also sneak up on us and may not necessarily cause symptoms. Some patients may even be diagnosed incidentally if they visit a medical provider for another reason and end up getting a scan. Sometimes, we can identify NETs in patients who are asymptomatic.

One other important topic is that about 30% to 40% of patients with NETs can actually secrete hormones, and the hormones themselves can cause symptoms. That’s in the name: neuroendocrine, endocrine meaning these tumors can secrete hormones. One of the classic examples is carcinoid syndrome, which is caused by the secretion of a hormone called serotonin. We measure that in the blood or the urine as something called 5-HIAA. Patients with carcinoid syndrome often experience flushing or diarrhea, which are very characteristic symptoms that providers look out for.

How are NETs typically diagnosed? What challenges exist in identifying them early on?

NETs are diagnosed like many cancers, using a combination of scans, and we also need a biopsy or surgical specimen to prove that it’s a NET. We rely on our pathologists to describe the cells and perform special testing after the tissue is examined under a microscope. There are very characteristic features of NETs that show us what grade they are (grade 1, 2 or 3) which indicates how rapidly the cancer cells are dividing. We also look at other characteristics that tell us if the tumor is well-differentiated, which tends to be slower-growing, or poorly differentiated, which tends to be faster-growing.

It’s a combination of imaging and pathology. One relevant point is that we’re actually seeing an increase in the number of NET diagnoses over the last 30 years, which I think is due to a few factors. One, we’re getting better at diagnosing them, and there has been increasing awareness about NETs across different medical disciplines. However, that alone isn’t enough to explain the rise. We are seeing this increase, but we don’t yet know why; it may be due to environmental factors or other causes, and we’re actively trying to learn more. A key takeaway is that the incidence (the number diagnosed per year) is increasing, and research is ongoing to better understand the reasons behind it.

What treatment options are currently available for these patients?

There are several treatments available for patients with NETs. The approach depends on some of the categories we just described, based on grade, whether hormones are being secreted, and stage, which we haven’t yet discussed. Stage refers to where in the body the cancer is located. I would say there are four main treatment categories.

The first includes somatostatin analogs, which are monthly injections of medication. The two main ones, Sandostatin (octreotide) and Somatuline Depot (lanreotide), are a form of hormone treatment (not chemotherapy) and help slow down neuroendocrine tumors while also treating symptoms caused by hormone excess. They serve a dual role. The second category is formal chemotherapy. The most common chemotherapy used for pancreatic NETs, which many listeners may have heard of, is CAPTEM (Xeloda [capecitabine] and Temodar [temozolomide]), which are both oral medications. IV chemotherapies are sometimes used for higher-grade, poorly differentiated endocrine carcinomas.

The third treatment category is biologics, targeted therapies that interfere with specific tumor growth pathways, usually in pill form. Examples include everolimus, Sutent (sunitinib), and Cabometyx (cabozantinib). The final category is radioligand therapy, or peptide receptor radionuclide therapy. This involves a molecule, similar to octreotide or lanreotide, attached to a radioisotope. It is infused intravenously (through an IV) and delivers highly targeted radiation to somatostatin receptors, which act as flags on the surface of neuroendocrine cells.

An important takeaway (and something I find very hopeful) is that in the past 10 to 15 years, we’ve seen an explosion of FDA approvals and new research in NETs. Patients may see several new FDA-approved treatments and clinical trials in their lifetime. I’m hopeful that we’ll continue to see additional FDA approvals in the coming years.

What is the importance of recognizing initiatives like Neuroendocrine Tumor Awareness Month and other awareness initiatives like this?

Raising awareness among physicians is critical, especially for cancers that are less common. NETs are rare by incidence, but increasing in prevalence, meaning the number of people alive with a NET, or who have had a NET, is growing. We want doctors to be more aware of NETs so they keep it on their list of possibilities when patients present with symptoms.

Increasing awareness is also important for patients, so they feel they’re receiving adequate education and know there are sufficient clinical trials available. It’s also important for funders of clinical trials, so they allocate resources toward investigating new treatments and understanding why people develop NETs. Awareness is important across the board, and in my experience, it has significantly increased over the last decade or so.

Are there any specific resources or initiatives that you want to call out to help patients and caregivers better understand this disease?

There are a couple of key takeaways to end on. For patients with NETs, because this is a less common cancer, I highly recommend having a NET expert on their care team. It doesn’t have to be the only physician they see; I partner with many local oncologists, and that’s a common model. Advocate for yourself and find someone who treats a lot of patients with NETs. I think that is incredibly useful and important.

There are several NET patient advocacy groups and physician professional societies that have patient education arms. Finding some of these organizations can be very helpful. For example, the North American Neuroendocrine Tumor Society, or NANETS, co-hosts patient events at several conferences throughout the year. The NET Research Foundation also hosts several patient events. LAC-NET, or Learning Advocacy Connect NET, organizes excellent patient programs. There are also many local community organizations and institution-based support groups.

I would suggest asking your physicians and visiting some of these national websites to learn more. Empowering yourself with information as a patient or caregiver is something you can control, and it can be very helpful in easing your mind and increasing awareness of available treatments and ongoing research.

Transcript has been edited for clarity and conciseness.

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