The Role of Surgery and Collaboration in NETs Treatment

A significant unmet need for the treatment of neuroendocrine tumors (NETs) remains to improve the quality of surgical evidence. The CUTNETs collaborative, a group of 27 centers across North America and Europe, seeks to fill these needs.

In an interview with Targeted Oncology®, Julie Hendrick-Hallet, MD, FRCSC, associate professor of surgery at the University of Toronto, and Stefano Partelli, MD, associate professor of medicine at the Università Vita-Salute San Raffaele, discuss the aims of the collaborative, including identifying high-risk patients and the development of better criteria for resectability of NETs.

Targeted Oncology: Could you provide an overview of your presentation? 

Julie Hendrick-Hallet, MD, FRCSC: The presentation we're giving here is a featured abstract reporting on the CUTNETs experience. That collaborative group that we've put together with 27 centers across North America and Europe [is trying] to enhance the quality of surgical evidence in the neuroendocrine tumor surgical care and try to catch up with [our] medical oncology colleagues.

Stefano Partelli, MD: The presentation was about the risk of recurrence after pancreatic surgery for pancreatic neuroendocrine tumor and was trying to give a different perspective about this tumor. [These] usually are tumor[s] that can be resected, and there is no multimodal approach for this lesion, so without preoperative or postoperative treatment. This different perspective is that we can identify a specific group of patients who are at high risk of recurrence, and in particular, early recurrence, thanks to specific features that can be retrieved preoperatively. And maybe this group of patients can benefit [from] a preoperative approach, [like] systemic therapy.

Hendrick-Hallet: That's setting the stage [for] one of the first collaborative research efforts that we're going to have as part of the CUTNETs collaborative, which is to develop better criteria for borderline resectable pancreatic neuroendocrine tumors so that we can build studies from that afterward.

Partelli: There is no agreement on this, what is resectable or not resectable, especially for pancreatic neuroendocrine tumor[s]. Of course, our effort is trying to standardize this definition in order to identify patients who can go [to] up-front surgery and patients who will benefit [from] preoperative treatments.

Hendrick-Hallet: [This is] just 1 example of all the work that we have ahead of us, which is collaborative.

Targeted Oncology: You mentioned collaboration. What is its importance, specifically, when treating neuroendocrine tumors?

Hendrick-Hallet: Neuroendocrine tumors are an uncommon type of cancer. I don't want to use the word rare anymore because they are not; their prevalence is now high, and their incidence has been increasing over the past decades, but it remains uncommon, and not many surgeons are used to treating it. There [are] pockets of expertise in high-volume centers across the world, but the reality is that we cannot study this disease by ourselves in 1 center or by 1 surgeon. And sadly, in surgical therapy, a lot of the evidence, the data we use for treatment, are based on single-center, single-surgeon case series often. The importance of collaboration is trying to bring the expertise and the perspective of many different expert groups, [as well as] a number of patients that we have to generate this data, because without it, we'll never be able to generate high-quality science the way that the medical oncology field has been able to do in the past decades in neuroendocrine tumors. So we need to catch up as surgeons and to do better. And I think we can only do that together.

Partelli: Another aim is trying to increase the level of education. A surgical approach for neuroendocrine tumors, especially for pancreatic neuroendocrine tumors, can be very slippery. The risk of giving inappropriate indications is very high. We know that the complication[s] of surgery can be important, so there is a need to educate surgeons all around the world about this tumor to give the right indication, [and] to know which other tumor[s] maybe should be referred to [a] specific multidisciplinary team in [a] high-volume center.

Targeted Oncology: Collectively, what unmet needs do you consider to be the biggest in your area of expertise? 

Hendrick-Hallet: From my perspective, right now, there [are] probably 2 I can think of. The first one is establishing the role of surgery and the outcomes after surgery, in particular quality of life for patients, and showing that surgery helps patients and doesn't hurt them. Because it's a different balance in neuroendocrine tumors; those [patients] will live a very long time with [the] disease, and there is an immense potential to harm them with an operation. So we need to make sure that we maintain that balance and study that prospectively.

The second one is combining surgery with other therapies, and how we do that with the best combination? What's the best sequence? [We] probably know that it will be positive to combine things, but we don't know how to do it right now, or how it's going to affect outcomes.

Partelli: There are many. Another one, probably a [more] technical need, is the lack of specific biomarkers that can identify those tumors [that] will progress and behave like a real, aggressive tumor [and] at the same time, tumors that are at high risk of recurrence. Basically, we don't have specific biomarkers; it will be very important to find this in order to again improve the appropriateness of indication, to know which tumors can be just observed and [which] tumors that need to be resected. I think this is another important field where research should be focused on.

Targeted Oncology: Beyond the primary tumor, how does the CUTNET approach, as outlined in the presentation, alter the management and sequencing of therapies for patients presenting with synchronous, high-volume hepatic metastases?

Hendrick-Hallet: I think surgery plays an important role in neuroendocrine tumors, in both the primary tumor and the metastases. That's what's unique about this disease, and also very motivating to treat [it]. That problem is often the ability to resect depends on the surgeon who sees a patient. [The] resectability is in the eye of the beholder, as they say, and if we could figure out a way to standardize this a little bit more [and] have objective criteria on how to select patients, both from an anatomic and biologic perspective, that would be 1 of the goals that I think we need to achieve. We know that there's a role for surgery. We just need to bring that to more patients in a more standardized form, so that you don't get too drastic [a] different answer depending [on] what side of the street you're consulting a surgeon, and that [would] be my ultimate approach for the work we're doing.

Partelli: I think it's [on] very, again, slippery ground, as Julie said. The role of surgery is important also in the presence of metastatic disease, but at the same time, we don't have strong evidence regarding the efficacy of surgery, and of course, we hope to have in the future robust evidence, but I think that there is still a long way to go. In the meantime, it is very important to, again, share the indications together with all the specialists who are dealing with this disease—oncologists, endocrinologists, and so on. With the multidisciplinary team, and before giving indication for surgery in these cases, I think it should be very clear which is the aim of surgery [as there] can be different aims. Especially the debulking surgery can be performed in order to reduce symptoms in functioning tumors, can be seen as a possibility to improve the efficacy of systemic treatment by reducing the burden of the disease, and in some very selected cases, also as the possibility for liver transplant, especially in very young patients, very selected one[s]. It is very important to have clear in mind [the] aims of surgery and to share the indication.

Hendrick-Hallet: That's why we need this collaborative as well. We have [patients] who are on [a] different end of the spectrum, even within the collaborative, and surgeons who do a lot of these surgeries and a lot of these patients have [a] very different approach, and finding [a] middle ground or different approaches for different types of patients, I think having all the perspectives that we bring from those 27 centers will be key in doing that.

REFERENCE:

Hendrick-Hallet J and Partelli S. Care of neuroendocrine tumors: the Collaborative of Surgical Teams for NeuroEndocrine Tumors (CUTNETs)/high-risk pancreatic NETs: who, why, and how? Presented at: 2025 NANETS Symposium; October 23-25, 2025; Austin, TX.