By Anna Greene, PhD, Director of Research, NETRF
Pancreatic neuroendocrine tumors (PanNETs) are a rare but increasingly detected cancer, thanks in part to more widespread and advanced imaging. Among them, small nonfunctional PanNETs (NF-PanNETs), tumors less than or equal to 2 cm in size, are often discovered incidentally and assumed to be low-risk. But new research, including a comprehensive review just published in Endocrine-Related Cancer by NETRF-funded researchers Aatur Singhi, MD, PhD, Christopher Heaphy, PhD, and others, challenges that assumption and underscores the need for a more nuanced approach to managing these tumors.
As an organization committed to advancing treatments for neuroendocrine tumors (NETs), NETRF highlights the significance of this research, which provides vital insights into the evolving management of small NF-PanNETs.
The Problem with Relying on Tumor Size Alone
Historically, tumor size has been the primary factor guiding treatment decisions: surgery for tumors larger than 2 cm, and personalized management for those smaller, which may include surveillance or surgery. However, recent evidence shows that size alone doesn’t predict whether a small tumor will behave benignly or metastasize. In fact, metastasis has been observed in up to 17% of small tumors. This variability leaves clinicians and patients in a precarious position: should they risk overtreatment through surgery or undertreatment by watchful waiting?
A New Generation of Biomarkers
Integrating biomarkers into clinical care could improve outcomes. The review highlights several molecular biomarkers that could revolutionize how we assess risk in small NF-PanNETs. Chief among them are ATRX and DAXX protein loss and alternative lengthening of telomeres (ALT).
These markers have been shown to be more reliable predictors of aggressive behavior and recurrence than size or grade alone. For example, tumors that are positive for ALT or exhibit ATRX/DAXX loss demonstrate significantly lower recurrence-free survival, even if they are under 2 cm in size.
What This Means for Patients
Incorporating these markers into clinical decision-making could better identify which small NF-PanNETs require immediate surgical intervention and which can be safely monitored. This is especially important given the high complication rates associated with pancreatic surgery, including pancreatic fistulas and other long-term side effects.
The potential for preoperative biopsies to assess these markers is encouraging, but not yet widespread in practice. Techniques like endoscopic ultrasound-guided fine-needle biopsies (EUS-FNB) are underutilized despite their ability to provide the necessary tissue for molecular testing.
Where Do We Go From Here?
To truly personalize care for patients with small NF-PanNETs, more prospective, multicenter studies are urgently needed to perform biopsies and investigate the use of biomarkers. Unfortunately, many studies still overlook the inclusion of molecular biomarkers.
NETRF believes that integrating clinical, histopathological, and molecular data into strong risk prediction tools is the future of personalized care. These tools can help identify which patients will benefit from surgery, which can safely avoid it, and how follow-up should be customized.
What NETRF Is Doing
For patients with small NF-PanNETs, size is only part of the story. Biomarker-driven approaches promise safer, more effective, and more personalized care, and NETRF is committed to making that promise a reality by continuing to actively fund studies aimed at validating and implementing biomarkers like ALT and ATRX/DAXX loss.
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