Short answer: A new MD Anderson study found no evidence that appendix cancer chemotherapy after surgery lowered the chance of relapse in people with localized appendiceal adenocarcinoma. Fewer than 1 in 10 of those patients relapsed at all, and tumor subtype and specific genetic changes were associated with relapse while several standard colorectal cancer risk factors were not.

My husband David had a right hemicolectomy for stage 3B goblet cell adenocarcinoma of the appendix and never had chemotherapy. That was Dr. JP Shen’s recommendation. At the time it felt like the loneliest decision in the world, because almost everyone we met with a colon cancer diagnosis at the same stage was being handed a chemo schedule. On September 9, 2026, Dr. Shen and his team published a study that gives real data for decisions like the one we faced.

The paper ran in JAMA Surgery and it is the largest look yet at localized appendiceal adenocarcinoma. I want to walk through what it actually says, what it does not say, and who it does not apply to.

One disclosure up front. Dr. JP Shen serves on Appendicure’s medical advisory board and on our board of directors, and he is a named investigator on our registry protocol. He had no role in this post. The study was funded by the Cancer Prevention and Research Institute of Texas, the Appendix Cancer Pseudomyxoma Peritonei Research Foundation, and Conquer Cancer, the ASCO Foundation.

What the study found about appendix cancer chemotherapy

The researchers went back through the records of 439 people treated at MD Anderson for stage I, II or III appendiceal adenocarcinoma between January 2000 and February 2024. The median age at diagnosis was 56.5 years, and it was an even split between men and women.

Of those 439, there were 202 who had their surgery at MD Anderson, so those are the ones the team could follow closely enough to count relapses. Nineteen of them, or 9.4 percent, had the cancer come back. The median follow-up was 62.6 months, or just over five years.

Then they compared the people who received chemotherapy after surgery with the people who did not. After accounting for the differences between those two groups, chemotherapy was not associated with a lower chance of relapse or with longer survival. The paper states that finding most directly for stage II disease, and the researchers checked it against a separate group of 128 stage II patients treated at Memorial Sloan Kettering, which supported the stage II result.

That wording matters. This was a retrospective study, meaning the researchers looked backward through charts rather than assigning people to chemotherapy or no chemotherapy ahead of time. What they found is an absence of evidence that chemotherapy helped. That is not the same thing as proof that it does nothing.

Dr. Shen put the larger point plainly in the MD Anderson release: “For too long, the outdated notion that appendix cancer behaves similarly to colon cancer has driven treatment decisions for our patients.”

The colon cancer warning signs mostly did not apply

If you have ever had a pathology report explained to you, you have probably heard about poor differentiation, perforation, lymphovascular invasion and perineural invasion. Those are the features oncologists watch in colorectal cancer, and finding one on your report is usually treated as bad news.

In this study, none of those four was significantly associated with the cancer coming back.

What was associated with relapse: lymph node involvement, more locally advanced tumors classified as T4, and histology. Recurrence was 6 percent in stage II and 19.5 percent in stage III, more than three times as high in the stage III group. Goblet cell tumors had the lowest relapse rate of any subtype. Mucinous and enteric type tumors came back more often.

So the risk factors that get borrowed from colon cancer and applied to appendix cancer mostly did not hold up here, while subtype did.

What the study found about TP53 and GNAS

The team looked at tumor sequencing alongside the pathology, and two specific mutations lined up with relapse.

In goblet cell adenocarcinoma, a TP53 mutation was associated with a higher chance of the cancer coming back. In tumors that were not goblet cell, a GNAS mutation was associated with higher relapse risk.

Both associations were large, and both came from small numbers of patients. The range of uncertainty around them is wide, wide enough that the true effect could be much smaller than the headline number suggests. These are associations worth studying further, not settled tests you can act on today.

Sacha El Khoury, the study’s first author, said it this way: “Appendiceal cancers are not all the same. When we consider tumor histology together with its molecular features, we can better identify which patients are truly at a higher risk of recurrence.”

That makes tumor sequencing worth discussing with your oncology team. If you have never had it done, or you are not sure what your report says, I wrote about what a wild type result actually means and about what to do when two biomarker tests disagree.

Who this study does not cover

Our community spans every appendiceal subtype, and a lot of the questions I get come from people this paper says nothing about.

Everyone in this study had localized disease, meaning stage I, II or III. If you have stage IV disease or pseudomyxoma peritonei, this study was not about you. Neither were appendiceal neuroendocrine tumors, sometimes called carcinoid. Neither were LAMN or HAMN without invasive cancer.

There are limits on the study itself too. The people who got chemotherapy got it because their doctors chose it, and those doctors may have been picking the patients they were most worried about. The primary group came from a single hospital, though the Memorial Sloan Kettering check helps for stage II. The authors say the findings need confirmation elsewhere, and I agree with them.

What I would do with this if it were my family

I would not change a single thing about my treatment because of a blog post, including this one. What I would do is bring the paper to my next appointment.

Three questions are worth asking. What subtype is my tumor, in the exact words on the pathology report. Has my tumor been sequenced, and what did it show for TP53 and GNAS. If chemotherapy after surgery has been recommended to me, what is the specific reason in my case, given this data.

If your oncologist recommends chemotherapy after reading this study, that is not them ignoring the evidence. One retrospective study does not overturn a treatment plan built around your particular tumor. It gives you a much better conversation to have. The appendix cancer chemotherapy decision is one of the few in this disease where you usually have time to think, so use it.

Appendiceal cancers are also not colorectal cancer, and the standard of care reference for this disease is the Godfrey and PSM Consortium 2025 consensus guidelines rather than colorectal protocols.

Why our registry cares about this

Sequencing data is exactly what the Appendicure Patient-Led Global Appendix Cancer Registry collects. Mutations, pathology, subtype, treatment, outcome. A study like this one is only possible because a large cancer center happened to have that information sitting in its own records for 24 years.

Most people with this disease are never treated at a large cancer center, so their data never lands anywhere a researcher can use it. The registry exists to change that. If TP53 in goblet cell tumors and GNAS in non-goblet tumors really are associated with relapse risk, a global dataset that includes patients from community hospitals in 52 countries could help answer that question, not just the records of the people who made it to Houston.

Common questions about appendix cancer chemotherapy after surgery

Does chemotherapy after surgery lower the risk of relapse in localized appendiceal adenocarcinoma?

This study did not find evidence that it did. Patients who received chemotherapy after surgery relapsed at about the same rate as those who did not. The study was retrospective, not a randomized trial, so it shows a lack of demonstrated benefit rather than proof of no benefit.

How often does localized appendiceal adenocarcinoma come back after surgery?

In this study, 19 of 202 patients, or 9.4 percent, had a recurrence over a median follow-up of 62.6 months. It was 6 percent for stage II and 19.5 percent for stage III.

Which patients had the highest risk of recurrence?

Patients with lymph node involvement, T4 tumors, and mucinous or enteric type histology. A TP53 mutation in goblet cell tumors and a GNAS mutation in tumors that were not goblet cell were also associated with relapse. Goblet cell tumors had the lowest relapse rate overall.

Do the usual colon cancer risk factors apply to appendiceal adenocarcinoma?

In this study, mostly no. Poor differentiation, perforation, lymphovascular invasion and perineural invasion are established risk factors in colorectal cancer, and none of them was significantly associated with relapse here.

Does this study apply to pseudomyxoma peritonei or stage IV appendix cancer?

No. Everyone in the study had localized stage I to III disease. Pseudomyxoma peritonei, stage IV disease, appendiceal neuroendocrine tumors, and LAMN or HAMN without invasive cancer were not part of this analysis.

Should I stop chemotherapy because of this study?

No. Take the paper to your oncologist and ask what it means for your specific tumor. A treatment decision belongs to you and your care team, not to a single retrospective study.

Source

El Khoury S, Fanaeian MM, Yousef M, et al. Risk of Relapse and Efficacy of Adjuvant Chemotherapy in Localized Appendiceal Adenocarcinoma. JAMA Surgery. Published September 9, 2026. doi:10.1001/jamasurg.2026.4000