Colorectal neuroendocrine tumors (NETs) are heterogeneous, with outcomes varying based on tumor location, size, and grade. These characteristics and quality-of-life (QOL) concerns influence the choice of resection techniques and therapies. Researchers at the 2025 ASCO Gastrointestinal Cancers Symposium reviewed the heterogeneity of colorectal NETs and the data on available and emerging therapies.

Following these presentations, featured expert Diane Reidy-Lagunes, MD, was interviewed by Conference Reporter Editor-in-Chief Tom Iarocci, MD. Clinical perspectives on these findings from Dr Reidy-Lagunes are presented here.

Colorectal NETs are uncommon and quite heterogeneous. Some patients can have terrific outcomes when appropriate treatment is provided, while others do not. A presentation at the 2025 ASCO Gastrointestinal Cancers Symposium by Jennifer A. Chan, MD, MPH, focused on defining different patient populations with colorectal NETs and using the best available data, sharing which treatments are right for each one. More patients have colorectal NETs that are found incidentally, likely due to an increase in screening and endoscopic procedures. Patients with incidentally found NETs tend to have good outcomes, as their NETs tend to be asymptomatic and have a diameter of less than 1 cm. Increased tumor size is an unfavorable feature, so NETs with diameters of greater than 1 cm, and certainly more than 2 cm, are more concerning.

We have to be very mindful not to affect a patient’s QOL when we treat small, lower-grade rectal NETs, and we need to consider the location of the NET and how far it is from the anal verge. Determining the type of polypectomy and/or surgery that would be needed in a patient who underwent an R1 resection, I think, is very important. This is because we do not want to treat a very indolent tumor with an aggressive approach if it means that the patient may have to deal with longer-term, bowel-related QOL issues. I have had patients who have had a R1 resection, but, given the location of the tumors very close to the anal verge, sometimes we scope to see if there is any sign of recurrence on repeat biopsies. We are more worried about tumors that are larger than 2 cm in diameter and are grade 2 or higher. In these cases, the risk of leaving the tumor may outweigh the QOL benefits, so I may be a little more aggressive.

Thankfully, there are now multiple different treatment options for colorectal NETS that are advanced and progressing, and we continue to add to those options, which is very exciting. Typically, first-line therapy for metastatic, unresectable, progressive NETs is with the SSAs lanreotide or octreotide because they improve progression-free survival and have favorable side-effect profiles. We also have ¹⁷⁷Lu-dotatate, which targets the SSTR, and targeted therapies such as everolimus. Further, we hope that cabozantinib will receive US Food and Drug Administration (FDA) approval very soon. And then, of course, there are clinical trials as well. Lastly, in the advanced setting, liver-directed therapy is a common treatment for both small bowel and colorectal NETs.

At the 2025 ASCO Gastrointestinal Cancers Symposium, results from the phase 3 STARTER-NET study of patients with grade 1 or 2 unresectable or recurrent gastroenteropancreatic NETS in the first-line setting were also presented (abstract 652). This study examined whether combining everolimus and lanreotide was better than using everolimus alone in patients with metastatic disease and a tumor Ki-67 index from 5% to 20%. Researchers found that progression-free survival and objective response rates were a little better with the addition of lanreotide to everolimus, which is important because sometimes we need to shrink the tumor for symptomatic relief.

We are very careful about trying to lower the risks of side effects, as we want to be able to use therapies for as long as possible in patients who can often be treated for many, many years. So, I am not sure that the combination of everolimus plus lanreotide early on would improve outcomes or patient QOL over lanreotide alone. Although STARTER-NET is interesting, I do not think that it is practice changing unless I have a patient with a higher-grade symptomatic tumor with disease outside the liver, for example, and I want more tumor shrinkage before maintenance therapy. I think that this would be an appropriate combination therapy to consider in that situation based on this very well-designed study. However, I am not sure that staying on this combination for a long time would necessarily help patients live better or longer. Thankfully, colorectal NETs are often asymptomatic and are not progressing, so I think that it is incredibly important for clinicians to pause and ask if a therapy is right for a patient with asymptomatic disease if they suddenly develop side effects from the treatment.