Rising Early-Onset Neuroendocrine Tumors: Symptom Burden & Care Disparities

Neuroendocrine tumors (NETs) are a diverse and often slow-growing group of malignancies, but their landscape is rapidly shifting. While historically considered diseases of older age, a growing body of evidence, including findings from the prospective NET-PRO database, suggests a significant rise in the incidence of early-onset NETs in younger patients. This demographic shift raises critical questions about disease biology, clinical presentation, and overall patient experience.

In an interview with Targeted Oncology, Udhayvir S. Grewal, MD, assistant professor at the Winship Cancer Institute of Emory University, delved into a key analysis of the NET-PRO cohort, focusing on the distinct challenges faced by this younger population. The findings reveal that patients with early-onset NETs not only present with unique sociodemographic profiles—showing a disproportionate prevalence among racial minorities such as Hispanic and non-Hispanic Black patients—but also bear a significantly higher symptom burden and experience differences in health-related quality of life compared with their older counterparts.

Understanding these differences, particularly the heightened prevalence of symptoms like diarrhea, pain, nausea and vomiting, and insomnia, is crucial for oncologists to tailor supportive care and therapeutic strategies. Ultimately, these insights reinforce the urgent need to prioritize the enrollment of younger patients and the systematic integration of patient-reported outcomes in future clinical trials to ensure treatments are both effective and generalizable to the evolving NET patient population.

Targeted Oncology: Could you provide some background on the study?

Udhayvir Grewal, MD: This is a study that we did using the NET-PRO database, which is a prospective cohort of patients with NETs that were recruited from 14 sites across the US. This study is looking at patient-reported outcomes, looking at symptom burden, quality of life, and care preferences among patients with neuroendocrine tumors. The focus of this current analysis was looking at symptom burden and health-related quality of life in patients with early-onsetNETs. We're seeing that there is a rise in the incidence of neuroendocrine tumors in younger patients, but there's very little data on whether these patients, when they develop NETs, [have] different biology and [a different] impact on overall quality of life. This analysis was focused on studying symptom burden and health-related quality of life in younger vsolder patients with NETs.

There was an identification of distinct sociodemographic profiles. Could you elaborate on what that means?

What we're seeing is [that] patients with early-onset NETs are more likely to be patients that identify as Hispanic or non-Hispanic Black. And this is not unique to NETs. Our group has done other studies, such as in early-onset cholangiocarcinoma and other [gastrointestinal (GI)] cancers, where we're seeing that the rise in incidence is more pronounced in patients representingracial minorities.

Did your study allow you to hypothesize [any] geological differences that might drive this early-onset population?

I think that'sa really important question, and that's something that is an active area of research [that is] trying to understand if there are biological differences and differences in etiology. Our study was more focused on studying symptom burden and health-related quality of life in early-onsetvs average-onsetNETs.

What were significant differences observed in the symptom burden profile between early-onset and later-onset disease in patients with neuroendocrine tumors, and how should medical oncologists adjust their symptom management and monitoring strategies?

I think the important message here is that we're noticing that there might be some biologic differences between early-onset neuroendocrine neoplasms and average-onset NETs.We're seeing that there was a significantly higher burden of diarrhea, pain, nausea and vomiting, [and] insomnia; these are all important symptoms that affect the quality of life of patients with NETs, and these appear to be more pronounced. These appear to be more prevalent in younger patients with NETs. Recognizing that these patients are more likely to suffer because of these symptoms, and these symptoms are more likely to have an impact on their quality of life, is important because that allows us to tailor supportive care strategies according to the age at onset.

How will the study's findings be incorporated into future clinical trial design?

We're seeing that more and more patients who are younger are being diagnosed with NETs. Historically, I don't have data to provide right now, but I think younger [patients] have not been represented well on existing clinical trials that have led to FDA approval of therapies that we are using today in clinics. So, as we move forward, I think we should prioritize the accrual of younger patients onto clinical trials so we're able to adequately assess the efficacy of our therapies, not just on their disease, but also on their quality of life once they're enrolled onto clinical trials. [T]hat will also help us ensure that the findings of these clinical trials are generalizable to the patients that we're seeing in clinic, which will now increasingly include younger patients with NETs. And I think the fact that we found that these patients were more likely to have a higher symptom burden compared to average-onset patients [with NETs] reinforces the importance of incorporation of patient-reported outcomes in clinical trials and assessing those simultaneously with disease-related outcomes such as [progression-free survival], response rate, etc. So, these are equally important, if not more, to assess on ongoing and future clinical trials.

What would your take-home message be for practicing oncologists?

The take-home message would be that we're seeing a rise in NETs in younger patients, and what the growing body of evidence suggests is that this is a different biology. [W]e're not just seeing those differences on studies that are looking at genomic assessment of these tumors. We're also seeing those in clinical studies such as ours, where we're seeing differences in symptom burden [and] we're looking at differences in health-related quality of life domains.

It’s it's important for us to tailor therapeutic strategies and supportive care strategies to the age of onset of disease so we're able to appropriately address the care needs of these patients with NETs, [specifically] early-onset NETs.

REFERENCE:
Grewal U. Distinct Sociodemographic, Symptom, and HRQoL Profiles in Early-Onset Neuroendocrine Tumors: Insights from the NET-PRO Study. Presented at: 2025 NANETS Symposium; October 23–25, 2025; Austin, TX.