A new MD Anderson study of 376 cytoreductive surgeries finds that CEA, CA19-9, and CA125, considered together and tracked over time, give surgeons and patients meaningful information about disease burden, surgical outcomes, and the years that follow.

FROM OUR COMMUNITY Many Appendicure members have watched their CEA, CA19-9, or CA125 numbers shift in the weeks before and after cytoreductive surgery. Some have lived with markers that never quite normalized. Others have had reassuring drops that matched what their surgeons saw in the operating room. If this study reflects your experience or contradicts it, we want to hear from you. Your story is part of how this community learns.

Cytoreductive surgery, often paired with HIPEC, is the standard of care for appendix cancer that has spread to the lining of the abdomen. The goal is to remove every visible tumor deposit. The challenge is that abdominal imaging cannot reliably show how much disease is present, and even after surgery, microscopic disease may remain. That uncertainty is the gap a new study from MD Anderson, published in JAMA Network Open on May 4, 2026, tries to help fill.

The researchers reviewed 376 cytoreductive surgeries performed on patients with appendiceal adenocarcinoma between 2016 and 2024, and asked a focused question. When CEA, CA19-9, and CA125 are measured before surgery and again afterward, what do those numbers actually predict? The answer, when the three markers are read together rather than one at a time, turns out to be quite a lot.

What the study looked at

Three serum tumor markers are routinely used in gastrointestinal cancers. CEA, or carcinoembryonic antigen, is produced at low levels by normal gut tissue and rises in many digestive cancers. CA19-9 is a sugar-based antigen often associated with pancreatic and other GI cancers. CA125 is most familiar from ovarian cancer, but is also released by tissues lining the abdominal cavity, making it relevant in peritoneal disease.

Each marker on its own can be inconsistent in appendix cancer. The MD Anderson team wanted to know what happens when clinicians do what they often do in practice anyway, which is considered all three together. They stratified surgeries by whether any of the three were elevated before surgery, whether any remained elevated afterward, and whether previously high markers normalized.

The cohort was large for this rare disease. Most surgeries (83 percent) included HIPEC, most often with mitomycin C. About 77 percent of surgeries achieved complete cytoreduction, defined as no visible disease larger than 2.5 millimeters remaining. Goblet cell adenocarcinoma cases were analyzed separately and are discussed at the end of this post.

What the markers revealed before surgery

Higher tumor burden, measured by the peritoneal cancer index, came with higher levels of all three markers. Patients with a PCI of 16 or above had meaningfully higher median CEA, CA19-9, and CA125 than patients with lower PCI scores. This confirms what surgeons have long suspected, that the markers do reflect disease burden in many appendix cancer patients, even if the relationship is imperfect.

More striking was what the markers predicted about the surgery itself. Among patients undergoing curative-intent CRS, only 1.1 percent had an incomplete cytoreduction when all three markers were normal beforehand. When any of the three was elevated, that figure rose to 15.5 percent. The authors describe this as a 14-fold greater risk of incomplete cytoreduction associated with preoperative marker elevation.

That number deserves context. Incomplete CRS was uncommon in this cohort overall, occurring in about 10 percent of curative-intent cases. The patients here were treated at a quaternary referral cancer center by surgeons who specialize in peritoneal surface malignancies. The point is not that elevated markers doom a surgery. It is that they identify a group that warrants closer preoperative discussion about what surgery can realistically accomplish.

KEY TAKEAWAY When all three markers were normal before surgery, the rate of incomplete cytoreduction in curative-intent cases was just over 1 percent. When any marker was elevated, the rate was about 15 percent. This is information patients and surgeons can use as part of preoperative planning.

Among patients who did go on to complete cytoreduction, those with elevated preoperative markers had shorter disease-free survival than those whose markers were all normal. At five years, 67 percent of patients with all-normal preoperative markers were still disease-free, compared with about 37 percent of those with any marker elevated. Preoperative marker elevation by itself was not associated with worse overall survival when the three were considered together, although elevated CA19-9 alone was.

One finding ran counter to expectation. Low-grade tumors had higher rates of elevated CEA and CA125 than high-grade tumors. The authors attribute this to selection. Low-grade appendix cancers are often operated on regardless of how widespread the disease is, while high-grade cancers tend to be taken to surgery only when the burden is more limited. As a result, the high-grade cases that reach the operating room often have lower PCI and lower marker levels. The lesson for patients is that grade and marker level are tracking different things, and both matter.

What the markers revealed after surgery

The postoperative findings were the most consequential. After cytoreduction, the percentage of patients with elevated markers dropped sharply across all three. CEA elevation went from 65 percent before surgery to 35 percent after. CA125 elevation fell from 30 percent to 6 percent. CA19-9 elevation dropped from 36 percent to 23 percent. Complete cytoreduction was much more likely than incomplete cytoreduction to result in normalized markers across the board.

When markers stayed elevated after surgery, outcomes were worse. Patients with any postoperative marker elevation had nearly four times the risk of recurrence and roughly four times the risk of death compared with patients whose markers were all normal afterward. Notably, no patient who had complete cytoreduction with persistently elevated markers remained disease-free five years out. Among those whose postoperative markers were all normal, about 45 percent were still disease-free at five years.

The relationship held up under statistical adjustment. Even after accounting for completeness of cytoreduction, peritoneal cancer index, tumor grade, and mucinous histology, postoperative marker elevation remained associated with significantly worse overall survival. This suggests the markers are capturing something about residual disease or tumor biology that the standard surgical and pathologic measures do not fully account for.

KEY TAKEAWAY Elevated tumor markers after CRS, even after a complete cytoreduction, were associated with much worse disease-free and overall survival. Patients in this group may benefit from more frequent surveillance and earlier conversations about additional treatment.

Equally important was what happened when markers that had been elevated before surgery normalized afterward. These patients did substantially better than those whose markers stayed elevated. The hazard ratio for death was about six times higher in patients without normalization compared with those whose markers normalized. The authors point out that this two-part view, looking at both preoperative and postoperative markers, gives a more complete picture than either alone.

A note on individual markers

Although the headline finding centers on the three markers as a set, the individual markers behaved somewhat differently. CEA elevation, both before and after surgery, was consistently associated with worse outcomes. CA19-9 elevation was strongly tied to overall survival. CA125 was more inconsistent. Preoperative CA125 elevation was not associated with shorter disease-free survival, and postoperative CA125 elevation was not either, although CA125 normalization was associated with improved overall survival.

The practical implication is that no single marker should be relied on in isolation. A patient whose CA125 has always been normal can still have meaningful information in their CEA and CA19-9 trends, and the reverse is also true. The authors recommend that all three be measured at regular intervals before and after CRS.

What this study could not tell us about goblet cell adenocarcinoma

Forty-five surgeries in this cohort were performed for goblet cell adenocarcinoma, and these were analyzed separately from the broader appendiceal adenocarcinoma group. In this smaller cohort, higher PCI was not associated with higher marker levels, and the survival analyses did not reach statistical significance. The authors are explicit that these findings reflect the limits of sample size, not evidence that markers are unhelpful in goblet cell disease.

For Appendicure community members living with goblet cell adenocarcinoma, this means the question of how to interpret CEA, CA19-9, and CA125 before and after CRS in your specific cancer remains open. Larger, GCA-focused studies are needed before we can draw the same kinds of conclusions for this subtype.

What this means for patients facing or recovering from CRS

If you are preparing for cytoreductive surgery, this study supports a few practical conversations with your care team. Knowing your CEA, CA19-9, and CA125 levels in advance, and asking how they figure into your surgeon’s preoperative assessment, may help you understand both the realistic goals of surgery and the level of certainty around them. If any are elevated, that is not a reason to forgo surgery. It is information to weigh.

If you have already had CRS, the findings argue for sustained attention to all three markers in follow-up. Persistently elevated markers, especially after a surgery that was described as complete, may warrant closer surveillance and earlier discussion of next steps. Markers that normalized are reassuring but not a guarantee, since recurrence still occurs in this group. The takeaway is not to read too much into any single number, but to watch the pattern over time across all three markers together.

Questions to ask your doctor

These questions are written with this study’s findings in mind. Your team may have already addressed some of them. Others may not apply to your situation. Take what is useful.

1. Were CEA, CA19-9, and CA125 measured before my surgery, and what were the results? Were any of them elevated?
2. Given my preoperative marker levels, what is your assessment of the likelihood of achieving a complete cytoreduction?
3. How will my markers be measured after surgery, and how often? What window after surgery do you consider most informative?
4. If a marker that was elevated before surgery normalizes afterward, how does that change your follow-up plan? What if it stays elevated?
5. If all three of my markers were normal before surgery, are there other measures (imaging, pathology features, molecular testing) you would weigh more heavily in my surveillance plan?
6. How do you interpret marker trends over time, and at what point would changes prompt additional imaging, additional treatment, or a referral for a clinical trial?
7. How do these findings apply (or not apply) to my specific subtype, particularly if I have goblet cell adenocarcinoma, signet ring cell carcinoma, or another less common pathology?

Why your data matters: the Appendicure registry

This study was possible because MD Anderson is a high-volume center with a research database large enough to detect patterns in a rare disease. Most appendix cancer patients are not treated at centers like that. Their data, and the lessons that data could teach, sit scattered across health systems where no one is positioned to put the picture together.

That is the gap the Appendicure Patient-Led Global Data Registry is built to close. By contributing your own information about diagnosis, treatment, and outcomes, you become part of a dataset that can answer questions this study could not. How do tumor markers behave in goblet cell adenocarcinoma specifically? Do the same patterns hold for signet ring cell carcinoma, or for patients treated at community hospitals rather than referral centers? Does timing of HIPEC, choice of agent, or patient subtype change what markers predict?

These are questions a single retrospective study, however well done, cannot answer alone. They require more patients, from more places, sharing their experience over time. If the findings in this study resonated with you, or did not match your experience, that is exactly the kind of information the registry is designed to capture. Click here if you live in the United States, or here if you live outside the United States, to make your data count.

ADD YOUR STORY Joining the Appendicure community data registry takes a few minutes and helps researchers ask better questions about appendix cancer subtypes that are too rare for any single center to study well. Visit appendicure.com to learn more and contribute. We are HIPAA compliant and your data is safe.

Glossary

Appendiceal adenocarcinoma (AA). A cancer arising from the gland-forming cells of the appendix. Includes mucinous, colonic-type, and signet ring cell subtypes.

CA125. A protein expressed by tissues lining the abdominal, chest, and pericardial cavities. Elevated levels can reflect peritoneal disease but are not specific to cancer.

CA19-9. A sugar antigen often elevated in pancreatic and other gastrointestinal cancers. Some patients (Lewis-negative) cannot produce it regardless of disease.

CEA (carcinoembryonic antigen). A protein normally produced by fetal tissue and at low levels in adult gut tissue. Often elevated in colorectal, appendiceal, and other GI cancers.

Complete cytoreduction (CCR 0/1). A cytoreductive surgery in which no visible tumor remains, or only deposits smaller than 2.5 millimeters.

CRS-HIPEC. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy. Visible tumor is surgically removed, and heated chemotherapy is then circulated through the abdominal cavity.

Disease-free survival (DFS). The length of time after treatment during which no signs of cancer recurrence are detected.

Goblet cell adenocarcinoma (GCA). A distinct subtype of appendix cancer with both adenocarcinoma and neuroendocrine features. Behaves differently from other appendiceal adenocarcinomas.

Hazard ratio (HR). A statistical measure comparing the risk of an event (such as recurrence or death) between two groups over time.

Overall survival (OS). The length of time from a defined starting point (such as surgery) until death from any cause.

Peritoneal cancer index (PCI). A score from 0 to 39 used during surgery to quantify how much tumor is present and where it is distributed in the abdomen.

Tumor marker (TM). A substance, usually a protein, that can be measured in the blood and may rise in the presence of certain cancers. Used to help track disease, not to diagnose it on its own.

Source

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. doi:10.1001/jamanetworkopen.2026.10569

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Medical disclaimer. This post is intended for educational purposes only and does not constitute medical advice. Information about appendix cancer, including tumor markers and CRS-HIPEC, evolves rapidly. Treatment decisions should always be made in consultation with a qualified medical team familiar with your individual case. Appendicure is a 501(c)(3) nonprofit dedicated to appendiceal cancer patient education and advocacy and is not a medical provider.