By Anna C. Greene, PhD, NETRF Chief Scientific Officer
Research is helping physicians make more informed decisions about how to treat and monitor neuroendocrine cancers. From identifying patients who may benefit from liver transplantation to tailoring post-surgery surveillance and assessing treatment response, recent studies highlight the growing importance of matching care to each patient’s disease.
In this month’s research roundup, the Neuroendocrine Tumor Research Foundation (NETRF) highlights four publications exploring how a better understanding of tumor biology and treatment response could guide more personalized care. Together, they span decisions about treatment and monitoring for neuroendocrine tumors (NETs) and early research into a potential treatment strategy for a rare neuroendocrine carcinoma (NEC).
Rethinking Liver Transplantation for Patients with Neuroendocrine Tumor Liver Metastases
For some patients with advanced neuroendocrine tumors, cancer that has spread to the liver can be particularly difficult to manage. A new position statement from the European Neuroendocrine Tumor Society (ENETS), led by Dr. Peter Stålberg of Uppsala University in Sweden and published in the Journal of Neuroendocrinology, examines when liver transplantation might offer meaningful benefits for patients with metastatic small intestinal or pancreatic NETs.
The authors emphasize that liver transplantation is rarely curative in this setting, and cancer recurrence remains common. However, transplantation may improve survival or control difficult symptoms in a carefully selected group of patients. Rather than relying only on traditional eligibility criteria, the statement recommends considering tumor biology, disease progression, the extent of liver involvement, and whether transplantation is likely to offer greater benefit than other available treatments.
Why it matters for patients: Liver transplantation is not appropriate for most people with metastatic NETs, but it may be an important option for a small subset of patients whose disease is largely confined to the liver and cannot be adequately managed with other treatments. The statement offers a framework for multidisciplinary teams to evaluate these complex decisions while acknowledging the risks of transplantation and the need for more evidence.
Read the ENETS position statement
Could a Simple Tumor Test Help Reduce Unnecessary Surveillance After Pancreatic NET Surgery?
Following surgery to remove a pancreatic neuroendocrine tumor, patients typically undergo years of imaging to monitor for recurrence. But not all tumors carry the same risk of returning, raising an important question: Could some patients safely undergo less frequent surveillance?
A study led by Anna Vera Ditte Verschuur and colleagues at University Medical Center Utrecht in the Netherlands, published in Endocrine Pathology, investigated whether testing tumor tissue for three proteins, ATRX, DAXX, and Menin, could help identify patients with a lower risk of recurrence. Researchers examined tumors from 139 patients who had undergone surgery for non-functioning, grade 1 or 2 pancreatic NETs without evidence of distant metastases at diagnosis.
The researchers identified a group of patients whose tumors had a particularly low risk of recurrence. None of the 33 patients whose tumors showed loss of a protein called Menin, while retaining ATRX and DAXX, experienced a recurrence during the study’s follow-up period. In contrast, nearly half of patients whose tumors showed loss of ATRX or DAXX experienced recurrence. These findings suggest that relatively simple laboratory tests could help distinguish pancreatic NETs with different risks of returning after surgery.
Importantly, the researchers used immunohistochemistry, a laboratory technique already widely available in pathology departments, rather than requiring more complex genomic testing.
Dr. Lodewijk Brosens, associate professor and clinical scientist at University Medical Center Utrecht, emphasized both the clinical potential and the need for further validation: “Routine pathology testing may help identify patients with non-functioning pancreatic neuroendocrine tumors who are at low risk of recurrence, opening the door to more personalized and less intensive surveillance. We are now validating these findings in an independent cohort to establish the evidence needed to safely reduce long-term surveillance for selected patients.”
Why it matters for patients: If validated in larger, prospective studies, these findings could help physicians better estimate recurrence risk and tailor surveillance after pancreatic NET surgery. Patients with lower-risk tumors might eventually be able to undergo fewer scans, potentially reducing anxiety, radiation exposure, and healthcare costs. For now, the results are promising but do not support changing surveillance schedules based on these markers alone.
Can Scans During PRRT Help Predict How Well Treatment Is Working?
Peptide receptor radionuclide therapy (PRRT) with lutetium-177 DOTATATE is an important treatment option for patients with advanced, somatostatin receptor-positive NETs. However, not every patient responds, and clinicians need better ways to determine whether it is working.
Dr. Udhayvir Grewal, now at Emory University, and colleagues at the University of Iowa explored whether conventional CT or MRI scans performed during PRRT could help predict treatment outcomes. Their findings were published in the World Journal of Nuclear Medicine. Researchers analyzed imaging results from 37 patients with well-differentiated NETs, most of whom underwent scans after two of their planned treatment cycles.
The researchers found that early imaging results generally aligned with outcomes after treatment. Nearly 94% of patients whose tumors had partially shrunk on interim scans maintained that response after PRRT, while approximately 92% of patients with stable disease remained stable.
Patients whose disease progressed during treatment generally had less favorable outcomes, although some subsequently achieved disease control. The researchers also identified cases of pseudoprogression, in which treatment-related changes made tumors temporarily appear larger even though the treatment was having a beneficial effect.
Why it matters for patients: Patients undergoing PRRT may have to wait until after treatment to learn how well it is working, a stressful period of uncertainty. This study suggests that CT or MRI scans performed during treatment could provide earlier insight into treatment response, potentially helping patients and their care teams make more informed decisions. Earlier imaging may also reassure patients when tumors shrink or remain stable, although the study did not directly assess patient anxiety.
Earlier recognition of disease progression might help clinicians reassess treatment strategies, while identifying pseudoprogression could help avoid unnecessarily stopping an effective therapy. Because this was a small, retrospective study, additional research is needed before interim imaging can routinely guide changes to PRRT treatment.
Exploring a New Treatment Strategy for Neuroendocrine Carcinoma of the Cervix
Neuroendocrine carcinoma of the cervix is a rare, aggressive cancer with limited treatment options. A study by Binhua Dong and colleagues at Fujian Medical University and collaborating institutions in China, published in Signal Transduction and Targeted Therapy, explored whether disrupting how these cancer cells repair damaged DNA could offer a new treatment approach.
The researchers found that these tumors had highly active DNA repair processes. They identified a protein called BLM that helped cancer cells withstand treatment with PARP inhibitors, drugs that interfere with DNA repair. Combining PARP and BLM inhibitors produced stronger anticancer effects in laboratory experiments, including patient-derived organoids, miniature tumor models grown from patients’ cells, and mouse models.
Why it matters for patients: This research identifies a potential treatment strategy for a rare neuroendocrine cancer that needs more effective therapies. However, the combination has not yet been shown to be safe or effective in patients. Further research is needed before it could become a treatment option, and whether the same approach could benefit NECs arising elsewhere remains an open question.
Moving Toward More Individualized Care
Although these studies examine different aspects of neuroendocrine cancer care, they share an important goal: helping physicians make better-informed decisions based on the characteristics of each patient’s disease.
Whether identifying who might benefit from an intensive intervention, determining who may need less surveillance, evaluating treatment response earlier, or uncovering potential treatment targets, these efforts support the development of more individualized care.
At NETRF, advancing precision medicine is a central part of our research mission. By supporting research that deepens our understanding of neuroendocrine cancers, we aim to help build a future in which patients receive the treatments and monitoring strategies best suited to their individual needs.
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Learn More from NETRF
Explore additional resources to better understand neuroendocrine cancer and treatment options:
NETWise Episode 17: Focus on Liver NETs
NETWise Episode 46: Understanding Neuroendocrine Carcinoma
You Ask, NETRF Answers: Is Neuroendocrine Carcinoma Different From a Neuroendocrine Tumor?
You Ask, NETRF Answers: What Happens After PRRT?
This article is intended for educational purposes and does not replace individualized medical advice. Patients should discuss treatment and surveillance decisions with their healthcare team.