APPENDICURE

Mucinous appendiceal adenocarcinoma survival has long been described in terms of two numbers: the Peritoneal Cancer Index and the completeness of the cytoreductive surgery. A new 198-patient series from the Washington Cancer Institute suggests that those numbers, while important, may not be doing as much of the prognostic work as the field has assumed.

Yesterday’s post looked at a Rome study finding that PCI loses its predictive grip past a score of 30 in low-grade pseudomyxoma peritonei. This week’s paper, from Paul Sugarbaker and David Chang, comes at a similar question from a different angle. In their cohort of 198 patients with mucinous appendiceal adenocarcinoma treated over 25 years, PCI did not significantly predict survival. Neither did preoperative tumor markers. What did matter was histologic subtype and whether the patient received HIPEC.

Two studies, two cohorts, two questions. The thread that connects them is worth pulling on.

What the 25-Year Mucinous Appendiceal Adenocarcinoma Series Looked At

Mucinous appendiceal adenocarcinoma, abbreviated MACA in the paper, is the histologic family that includes well-differentiated (grade 1), moderately differentiated (grade 2), poorly differentiated (grade 3), and signet ring cell variants. The authors also use an intermediate category, MACA-Int, which sits between the classical low-grade and high-grade designations. About 30 percent of patients with pseudomyxoma peritonei have MACA histology rather than the more indolent LAMN tumors covered in Part I of this series.

All 198 patients in the study had a complete cytoreductive surgery. Preoperative clinical features and tumor markers (CEA, CA19-9, CA125) were recorded in the week before the operation. Perioperative intraperitoneal chemotherapy, histologic findings, and any reoperative surgery were captured afterward. The authors then ran univariate and multivariate analyses to see which variables actually moved overall survival.

The median overall survival across the cohort was 11 years. That number alone is worth sitting with. It is the kind of long-horizon outcome that patients ask for and rarely see cleanly published in mucinous appendiceal adenocarcinoma survival data.

PCI and Tumor Markers Did Not Predict Mucinous Appendiceal Adenocarcinoma Survival

In a single-center series of nearly 200 patients, the Peritoneal Cancer Index did not significantly affect overall survival. Neither did preoperative CEA, CA19-9, or CA125, individually or in combination.

This is a striking finding, and it needs to be read carefully. The authors are not saying PCI is useless. They are saying that within a population of MACA patients who all received a complete cytoreductive surgery at a high-volume center, the PCI number did not separate longer survivors from shorter survivors.

Read alongside yesterday’s Rome paper, a pattern starts to emerge. In LAMN-origin pseudomyxoma peritonei, the Rome group found that PCI predicted survival across the full cohort but lost discriminatory power past PCI 30. In MACA-origin pseudomyxoma peritonei at the Washington series, PCI did not significantly predict survival at all. Neither study argues that PCI should be abandoned in surgical planning, because the score still describes how much work the operation will involve and helps assess whether complete cytoreduction is feasible. Both studies suggest, though, that once you condition on getting a complete cytoreduction, PCI carries less prognostic weight than the field has historically given it.

The takeaway in plain terms For patients with mucinous appendiceal adenocarcinoma who are able to undergo a complete cytoreduction, what the tumor is made of and how it is treated intraoperatively appears to matter more for survival than how much disease was there to begin with. Tumor markers drawn before surgery did not help predict outcome.

HIPEC Versus EPIC: A 12-Year Versus 4-Year Gap in Mucinous Appendiceal Adenocarcinoma Survival

The largest single difference in the study was between two methods of delivering intraperitoneal chemotherapy at the time of surgery. Patients who received HIPEC, hyperthermic intraperitoneal chemotherapy delivered as heated solution during the operation, had a median survival of 12 years. Patients who received EPIC, early postoperative intraperitoneal chemotherapy delivered through catheters in the days immediately after surgery, had a median survival of 4 years. The hazard ratio was 2.09 with a p-value of 0.002, meaning the difference is statistically significant and not likely to be a chance finding.

EPIC is not commonly used as standalone perioperative chemotherapy at most contemporary peritoneal surface programs in the United States. HIPEC has become the dominant approach, and this paper supports that pattern strongly within MACA-origin disease. For patients comparing centers or asking what perioperative chemotherapy approach a program uses, the data here weighs heavily in favor of HIPEC when thinking about mucinous appendiceal adenocarcinoma survival.

A few caveats are worth flagging. The 25-year window means the EPIC patients were generally treated earlier in the series, when surgical technique, patient selection, and supportive care were different than they are today. Some of the survival gap may reflect era effects rather than the chemotherapy modality itself. The authors do not break out the data in a way that fully separates these factors. Even so, the gap is large enough that it is hard to attribute entirely to confounding.

Histology and the Intermediate Subtype

The second strong finding from the Washington series was about histology. The MACA-Int subtype, the intermediate category between well-differentiated and high-grade tumors, was associated with the longest survival of any histologic group in the cohort. MACA-3, the poorly differentiated subtype, was associated with the shortest survival.

This continues a conversation Appendicure has been engaged in for some time. The three-tier WHO grading system (G1, G2, G3) is meant to capture the meaningful differences in tumor biology, but in research literature and in trial eligibility criteria, the moderately differentiated tier is often collapsed into the high-grade category. That practice obscures real differences in mucinous appendiceal adenocarcinoma survival. The Sugarbaker series, in identifying the intermediate subtype as the longest-surviving group in the MACA family, is another piece of evidence that the middle tier deserves to be named and described, not folded into a binary.

For patients with appendiceal cancer working from a pathology report, this matters at the level of language. A report that says “mucinous adenocarcinoma, intermediate grade” or “moderately differentiated” is describing a tumor with different expected behavior than one labeled “high grade” or “poorly differentiated.” The distinction is worth confirming with the treating team, and worth asking about explicitly when reading a second opinion or a pathology re-read.

How the Two Studies Fit Together

Yesterday’s Rome paper and this week’s Washington paper come from different programs, different histologic populations, and different statistical approaches. They are not telling the same story, but they are telling stories with the same shape.

In LAMN-origin pseudomyxoma peritonei, the Rome group found that PCI mattered up to a point, and then anatomy of disease distribution took over as the dominant prognostic signal at very high tumor burden. In the Washington mucinous appendiceal adenocarcinoma survival data, PCI did not significantly drive survival across the whole spectrum, while histology and the choice of intraoperative chemotherapy did.

Both findings push in the same direction. The classical surgical-burden metrics, PCI and to a lesser degree CC score, are real and useful, but they are not the whole prognostic picture, especially once you select for patients who can get a complete cytoreduction. Biology, location, and the details of how the operation is performed are doing more of the predictive work than the field has historically credited them with.

This is consistent with what high-volume peritoneal surface programs have been saying in conference talks for several years. Two papers in two weeks now put that conversation on paper.

What These Studies Cannot Tell Us About Mucinous Appendiceal Adenocarcinoma Survival

The Washington series is a single-institution retrospective review of patients treated by one of the founding programs in peritoneal surface oncology. Sugarbaker’s outcomes are not generalizable to most centers. Surgical experience, case volume, and decades of institutional learning shape what is achievable in his operating room in ways that smaller programs cannot replicate. Findings from a 198-patient cohort at a high-volume reference center are best read as what is possible at that center, not what is typical across centers.

The 25-year time window also raises real questions. Surgical technique, anesthesia, critical care, imaging, and patient selection have all changed substantially since the early 2000s. Some of the survival differences observed in the cohort, particularly between HIPEC and EPIC, may reflect those era effects in addition to or instead of the variables the authors highlight.

Neither study changes who should be offered cytoreductive surgery, and neither replaces PCI or CC scoring as part of surgical planning. PCI is still how surgical teams describe and stage the operation. CC score is still how the outcome of the surgery is described. What is shifting is how much prognostic weight those numbers should carry in conversations about mucinous appendiceal adenocarcinoma survival afterward.

Questions to Bring to Your Surgical Consult

For patients with mucinous appendiceal adenocarcinoma considering cytoreductive surgery, the questions worth bringing into a consultation have shifted with these findings. The following can be used alongside the questions from Part I of this series.

What is my specific histologic subtype, and how is it described in my pathology report?

If my tumor is described as moderately differentiated or intermediate grade, what does that mean for my expected course?

Does your program use HIPEC, EPIC, or another perioperative chemotherapy approach?

If HIPEC, what drug regimen do you use, and at what temperature and duration?

How many MACA cases does your center treat each year, and how many over the past five years?

How do you think about PCI in my case, and what role does it play in your surgical plan?

Has my pathology been reviewed at your center, or by a pathologist who specializes in appendiceal tumors?

Closing Thoughts on Mucinous Appendiceal Adenocarcinoma Survival

Two papers in two weeks do not change the standard of care. They do, however, change the texture of how patients and clinicians can talk about prognosis. The questions worth asking are getting more specific, and the answers are getting more nuanced.

If Part I was about location mattering more than volume at the extreme end, Part II is about biology mattering more than burden across the spectrum, at least in the cohort the Washington group has been treating for a quarter century. Both posts point at the same broader idea. In appendiceal cancer, the easy numbers are not the whole story, and the patients living with this disease deserve a conversation that reflects that.

Appendicure will continue to track this literature as it develops. If validation comes from other high-volume centers, the prognostic vocabulary used in patient-facing materials and surgeon consultations will need to catch up to what the data on mucinous appendiceal adenocarcinoma survival is now showing.

Read Part 1 Here: Pseudomyxoma Peritonei PCI: When the Number Stops Telling the Whole Story – 1 New Study

Glossary

MACA	Mucinous Appendiceal Adenocarcinoma. The histologic family of mucin-producing adenocarcinomas arising from the appendix, including well-differentiated, intermediate, moderately differentiated, poorly differentiated, and signet ring cell variants.
MACA-Int	The intermediate-grade subtype within MACA. Sits between the classical low-grade and high-grade designations and, in the Washington series, was associated with the longest survival of any MACA subtype.
PCI	Peritoneal Cancer Index. A surgical scoring system that divides the abdomen into 13 regions and assigns 0 to 3 points per region based on the size of tumor deposits. Maximum score is 39.
CC score	Completeness of Cytoreduction. A measure of how much visible disease remained after surgery. CC-0 means no visible residual disease.
HIPEC	Hyperthermic Intraperitoneal Chemotherapy. Heated chemotherapy delivered into the abdominal cavity at the end of cytoreductive surgery to address microscopic residual disease.
EPIC	Early Postoperative Intraperitoneal Chemotherapy. Non-heated chemotherapy delivered through catheters into the abdominal cavity in the days immediately following cytoreductive surgery.
CEA, CA19-9, CA125	Blood-based tumor markers sometimes elevated in appendiceal and other gastrointestinal cancers. Used for monitoring and, less reliably, for prognosis.
LAMN	Low-grade Appendiceal Mucinous Neoplasm. A low-grade tumor of the appendix that can rupture and seed the peritoneal cavity. Covered in Part I of this series.
PMP	Pseudomyxoma Peritonei. A clinical syndrome characterized by progressive accumulation of mucinous material throughout the peritoneal cavity, most often from a ruptured appendiceal neoplasm.

Sources

Sugarbaker PH, Chang D. Assessment of Outcome in 198 Patients With Mucinous Appendiceal Adenocarcinoma and Peritoneal Metastases Over 25 Years. Journal of Surgical Oncology. 2026. DOI: 10.1002/jso.70283

D’Annibale G, Abatini C, Lodoli C, et al. Prognostic Ceiling Effect of the Peritoneal Cancer Index in Super-Extended Pseudomyxoma Peritonei of Appendiceal Origin. Journal of Gastrointestinal Surgery. 2026. DOI: 10.1016/j.gassur.2026.102456

Internal link to add at publish time: Link the phrase “Part I of this series” (appears in body) to the Part I post URL.

Appendicure

Patient education and advocacy for appendiceal cancer