Patients with carcinoid syndrome are classified according to the tumor biology, disease sites, and tumor burden. We think about both the tumor burden and the syndromic burden, and there is often—but not always—an association between the two.

Metastatic spread from the primary tumor to the lymph nodes and liver is common. By evaluating the patient with a computed tomography (CT) scan or a DOTATATE positron emission tomography (PET)/CT scan, we get an idea of what percentage of the liver is involved. Based on the initial assessment, the approach entails matching the patient’s disease bulk and symptoms to an individualized treatment plan. And then we reassess on an ongoing basis. If a patient with carcinoid syndrome is symptomatic, we will usually use somatostatin analogues (SSAs). If there is significant disease bulk, we have to consider locoregional therapy. If they have an intact primary tumor, we may consider removal.

In that initial assessment, we also will include an evaluation to detect carcinoid heart disease based on the patient's current serotonin levels, how high those levels have been, and for how long. This involves getting an echocardiogram and assessing the tricuspid and the pulmonic valves in particular to look for signs of insufficiency or regurgitation. I think that important components of a comprehensive initial care plan include looking at the echocardiogram, CT scan or DOTATATE PET/CT scan, labs, and signs of disease burden, and then controlling symptoms and potentially planning an elective procedure for a primary resection.

Whether the patient has symptoms due to carcinoid syndrome or tumor bulk, we have a whole set of management strategies to try to deal with that, as Dr Anthony detailed. And, of course, recognizing the early symptoms of carcinoid heart disease (eg, fatigue) is also crucial.

I think that it is important to provide patients with some type of "outline" for the future. During the initial visits, we focus on trying to help relieve and improve whatever physical symptom burden(s) the patients have, and we also focus on helping them understand that this is a very unique type of malignancy. This is something unlike any other cancer with which they, their friends, or their family are likely to be familiar. So, again, we try to help them understand and be hopeful about what is to come. There are many patients whose physical symptomatic burden is very well controlled with treatment, for whom the psychologic burden of living with uncertainty becomes the most significant burden.

It is important to convey that, even though their disease is not currently curable, many patients with carcinoid syndrome live 5, 10, 15, or even 20 years after it is detected, and that is with using established strategies. Hopefully, these patients can live long enough to benefit from new drug discoveries and new treatments that might take years to develop and could potentially prolong their survival even further. And there is realistic hope of patients living many good years even after it spreads to the liver, which is something that people often connect with very dire circumstances based on the behavior of other cancers. However, in a well-differentiated NET, a patient can live very well for a long time after developing liver metastases.

There is definitely a correlation between the metastatic tumor burden, in the liver and elsewhere, and carcinoid syndrome. Clearly, we do have some patients with low-volume disease who have more significant symptoms and other patients with high-volume disease who have a lower symptom burden, but, on average, there is a correlation.

There are many different factors that influence the approach to treatment, but the standard treatment for metastatic unresectable NETs with carcinoid syndrome is an SSA, for both control of the syndrome and stabilization of tumor growth. Beyond that, if there is a significant disease burden in the liver in a patient who is symptomatic, we would often consider a liver-directed therapy such as hepatic arterial embolization. If there is disease progression in a patient on SSA therapy, another option would be lutetium-177–DOTATATE, which is a radiolabeled SSA. We also have telotristat, which is used to control carcinoid syndrome–related diarrhea.

If a patient has increased symptoms but their disease is otherwise relatively stable, there are a number of options that we can consider to lower the symptom burden. For instance, adding telotristat to SSA therapy may help control the patient's diarrhea. Consideration could also be given to increasing the dose or frequency of an SSA. Short-acting octreotide could be prescribed in addition to a long-acting formulation, or liver embolization may be an option if the disease is mostly in the liver and the symptoms are progressive.