APPENDICURE

The appendix cancer ASCO 2026 story is not about a new drug. ASCO’s two 2026 meetings, the Gastrointestinal Cancers Symposium in January and the Annual Meeting in late May, did not produce a new approved treatment for the disease. That is not surprising, because it is rare enough that it almost never gets a major drug trial of its own. What did come through is a set of findings that sharpen how doctors estimate risk, push back on the long habit of treating appendix cancer like colon cancer, and document where patients are still falling through the cracks. Here is what is worth your attention, and what each finding does and does not mean.

Tumor markers deserve more respect than patients have been told

For years, many appendix cancer patients have been told that blood tumor markers are not very useful. A 2026 analysis from MD Anderson pushes hard against that idea. Looking at CEA, CA19-9, and CA125 measured before and after cytoreductive surgery with HIPEC in appendiceal adenocarcinoma, the group found that elevated markers tracked with higher tumor burden, a lower chance of achieving a complete cytoreduction, and worse recurrence-free and overall survival. Patients whose markers normalized after surgery did meaningfully better than those whose markers stayed up.

This is not a practice-changing guideline, and it should not be read as one. It is one of the more immediately usable findings of the year, because it gives patients a concrete reason to ask that these markers be checked during workup and tracked during surveillance, and to ask what a persistent elevation might mean for closer monitoring or a clinical trial conversation. The caveat is that this work is in adenocarcinoma, markers behave differently across the appendiceal subtypes, and no single value should be over-read in isolation.

Grade 2 mucinous disease is not high-grade disease

At the January GI symposium, investigators from MD Anderson used genomic and transcriptomic data from the Tempus database to compare the appendiceal subtypes against each other. The finding that matters most for patients is straightforward. Grade 2 mucinous adenocarcinoma looked like grade 1, not grade 3, in both its genetics and its survival. That supports keeping a three-tier grading system rather than collapsing grade 2 and grade 3 together into a single high-grade category.

A grade 2 mucinous diagnosis is not the same as a high-grade diagnosis, and that distinction can change how you are counseled about prognosis and treatment.

This lines up with how the Godfrey and PSM Consortium 2025 consensus handles grade, and it matters in a very practical way. A patient with grade 2 mucinous disease who is told they have “high-grade” cancer can walk out with a harsher prognosis and a more aggressive treatment frame than their tumor actually warrants. The same analysis also found that the subtypes carry distinct DNA changes, most often in KRAS, TP53, SMAD4, and GNAS, and that patients whose tumors carried both KRAS and GNAS mutations had better survival and a more favorable immune profile. The authors read that as a reason to keep studying immunotherapy in this disease. This is a link between genetics and survival, not a treatment result, so it points research in a direction rather than changing anyone’s care today.

Early-stage disease should not be treated with the colon cancer playbook

Also at the 2026 GI symposium, MD Anderson reviewed early-stage appendiceal adenocarcinoma. Relapse risk after surgery was low, and it was especially low in goblet cell adenocarcinoma. Stage III relapsed more often than stage II, which is expected. The part that challenges current practice is what happened in stage II. The “high-risk features” that oncologists borrow from colon cancer did not predict relapse well in appendiceal disease, and adjuvant chemotherapy showed no recurrence-free or overall survival benefit in stage II or in the high-risk stage II subset.

The takeaway for patients is that the reflex to treat early-stage appendix cancer with a colon cancer chemotherapy approach does not hold up well here. Together with the grading finding, this is really one theme repeating itself: appendix cancer needs its own evidence base rather than borrowed assumptions. This was a retrospective look at early-stage disease, so it does not speak to advanced disease or to the harder question of chemotherapy timing in higher-grade cancers headed for surgery.

That harder question is still open. A University of Pittsburgh group examined perioperative chemotherapy in grade 2 and grade 3 appendiceal cancers treated with CRS and HIPEC. The publicly available detail is not enough to fairly summarize the results yet, so the honest statement is that the question is being studied, not answered. One thing to keep in mind whenever you read retrospective chemotherapy outcomes is that sicker patients with more aggressive disease are the ones more likely to be given chemotherapy in the first place, which can make chemotherapy look worse than it is. The early-stage finding above and this advanced-disease question are two different settings, and neither one means chemotherapy never helps.

Access and geography still decide too much

Two studies this year put numbers on a problem the community already knows in its bones. Using the Nationwide Inpatient Sample from 2016 through 2021, one analysis estimated roughly 17,115 appendiceal adenocarcinoma hospitalizations, a 26 percent increase over the period, with in-hospital mortality around 1.5 percent, a median length of stay of five days, and inpatient costs above 1.7 billion dollars. It also flagged that CRS and HIPEC are under-captured and unevenly used in this kind of administrative data. A separate mortality-trends analysis found that appendix cancer deaths are rising in the United States, with rural areas showing the highest age-adjusted mortality in 2020 and a marked increase after 2004.

For patients and families, this is the data behind a familiar frustration. Getting to a specialized peritoneal surface malignancy center, and getting there in time, still depends too much on where you live and on whether the first doctor you see knows where to refer you. This is exactly the kind of evidence Appendicure can carry into advocacy on referral pathways and rural access. The honest limit is that administrative and registry data miss things, including procedures done outside the inpatient setting and cases that are miscoded, so the real picture of specialist access is likely even rougher than these numbers suggest.

Immune biology is becoming a serious line of work

At the Annual Meeting, a team led by researchers at Allegheny Health Network reported on tumor-associated macrophages in 112 appendiceal cancer specimens. Macrophages are immune cells that settle into different functional states. The M1 state is generally inflammatory and is usually assumed to oppose tumors, while the M2 state is generally tied to tissue repair and is usually assumed to help tumors grow. In appendiceal cancer, the M2 type outnumbered the M1 type, and the imbalance was strongest in peritoneal metastases, regardless of tumor grade or subtype.

The surprising part was what these patterns meant for survival. The usual assumption that more M2 macrophages signals a worse outcome did not hold here. Patients with very low M1 levels did worse, but higher M2 levels, and especially a high level of both M1 and M2 together, were associated with better overall survival, even after accounting for age, grade, and how far the disease had spread. This is one more sign that appendiceal cancer does not follow the rules written for other tumors. The group also tied distinct metabolic signatures to each macrophage state, and in an early trial they showed that activating the immune system directly inside the tumor shifted the macrophage makeup, which hints that this environment might eventually be adjusted for treatment.

This is translational research, a detailed map of the immune terrain rather than a treatment you can ask for. It is worth following because one of the most stubborn questions in appendix cancer is why checkpoint immunotherapy helps only a small subset of patients. Understanding the immune environment is the kind of groundwork that has to happen before anyone can design smarter immune-directed strategies for this disease. It is early and descriptive, and it needs to be validated in larger groups before it changes anything.

What we are watching, with a caution attached

The loudest gastrointestinal story at the Annual Meeting was not about appendix cancer at all. It was daraxonrasib, a pan-RAS inhibitor, which in the RASolute 302 trial roughly doubled overall survival in metastatic pancreatic cancer, about 13.2 months versus 6.7 months, while also doubling progression-free survival and nearly tripling the response rate. The full plenary data held up to its earlier preview, and some analysts expect the drug could reach patients as soon as later this year. It is on our radar because the same drug class is now being studied directly in appendiceal cancer. A Yale phase II trial is testing daraxonrasib in appendiceal patients, and a recent preprint from MD Anderson investigators, not yet peer reviewed, reported that blocking KRAS slowed appendiceal tumors in laboratory and animal models and lowered tumor markers in a small group of heavily pretreated patients.

The caution matters as much as the news, and that same MD Anderson work makes the point cleanly. KRAS mutations are common in mucinous appendiceal cancer, where they show up in roughly 80 percent of tumors, but they are uncommon in goblet cell disease. A drug aimed at KRAS therefore carries very different potential from one appendiceal subtype to the next, and the dramatic pancreatic result does not transfer directly or evenly to appendix cancer. The early appendiceal data are preliminary, drawn from laboratory models and a handful of patients, and resistance to these drugs already appeared in the same study. We will cover this drug class on its own terms in a dedicated post, rather than borrowing pancreatic numbers and hoping they apply.

The throughline

The 2026 appendix cancer story is not a breakthrough drug. It is a field beginning to treat this disease as its own thing, with its own grading, its own evidence on chemotherapy, and its own immune biology, while the data on access keep showing that patients are not all reaching the right centers. For patients and caregivers, the practical points are concrete. Tumor markers are worth tracking. A grade 2 mucinous diagnosis is not the same as high-grade. Early-stage disease may not need the colon cancer chemotherapy reflex. And where you are treated still matters more than it should.

If your family is living with appendix cancer, you can help build the evidence base this field still lacks by joining the Appendicure patient data registry.

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Read more from Appendicure

The Rarest of the Rare: understanding signet ring appendix cancer

Studies referenced

Pattalachinti VK, Seldomridge A, Yousef A, et al. Appendiceal adenocarcinoma cytoreduction outcomes and perioperative serum tumor marker levels. JAMA Network Open. 2026;9(5):e2610569. Link

Overman MJ, Shen JP, et al. Genomic profiling of epithelial neoplasms of the appendix. ASCO GI Cancers Symposium 2026, Abstract 847. Link

Early-stage appendiceal adenocarcinoma: relapse risk and adjuvant chemotherapy. MD Anderson. ASCO GI Cancers Symposium 2026, Abstract 840. Link

Perioperative chemotherapy in grade 2/3 appendiceal cancer undergoing CRS/HIPEC. University of Pittsburgh. ASCO Annual Meeting 2026, Abstract e15522. Link

National inpatient trends and disparities in appendiceal adenocarcinoma. ASCO Annual Meeting 2026, Abstract e23356. Link

Trends and disparities in appendiceal cancer deaths. ASCO Annual Meeting 2026, Abstract e15678. Link

Wagner P, et al. TAMs in appendiceal cancer: association with metabolic remodeling, prognosis, and response to intra-tumoral therapy. ASCO Annual Meeting 2026, Abstract 3597. Link

RASolute 302, phase 3 trial of daraxonrasib in metastatic pancreatic cancer (Wolpin et al.). Results were presented at the 2026 ASCO plenary (LBA5) and published in the New England Journal of Medicine. The linked abstract is the 2025 trial-in-progress writeup. Link

Chowdhury S, Ito I, Shen JP, et al. KRAS inhibition is an effective therapy for appendiceal adenocarcinoma. bioRxiv preprint, 2026. doi:10.64898/2026.04.07.717107 (preprint, not yet peer reviewed). Link