APPENDICURE

New research is raising an uncomfortable question. Are some appendix cancer patients, especially men, missing an important tumor marker because of an outdated assumption about who it’s for?

For years, appendix cancer patients have had their bloodwork monitored with tumor markers like CEA and CA19-9. CA125, historically associated with ovarian cancer, has not always been routinely ordered for men. Multiple studies, including work out of MD Anderson and The Christie in Manchester, suggest that needs to change.

A new commentary in JAMA Network Open this May addressed the issue directly. Omer Aziz, a peritoneal surgical oncologist at The Christie, wrote that ordering CA125 in male patients “may be met with resistance in many hospital laboratories across the world,” but that the evidence now justifies it.

I had no idea this was an issue because David has had all three from the beginning. This matters because appendix cancer doesn’t follow the same rules as more common cancers and apparently many smaller institutions are not following the new guidelines.

The issue at the center of this discussion

Most hospitals and oncology practices don’t have standardized appendix cancer protocols, because the disease is rare. So practice varies. Some physicians order only CEA. Some order CEA and CA19-9. High-volume appendix cancer centers tend to order all three: CEA, CA19-9, and CA125.

The inconsistency falls hardest on men, because CA125 is still widely categorized as a women’s cancer marker. Appendiceal adenocarcinoma spreads throughout the peritoneal cavity, the lining of the abdomen, and CA125 may reflect peritoneal disease activity regardless of sex.

What the new research found

The commentary discusses a 2026 MD Anderson study of 376 patients who underwent CRS with HIPEC for appendiceal adenocarcinoma. Patients with any of the three markers elevated before surgery had significantly worse disease-free survival. Patients with any of the three markers elevated after surgery had significantly worse overall survival. The associations held in both men and women, and all three markers tracked with tumor burden as measured by Peritoneal Cancer Index score.

The accompanying commentary went further. Aziz argued that all three markers should be measured before surgery, all three should be followed during postoperative surveillance, and that CA125 testing in men is justified by the available evidence.

This isn’t a single-study finding. A larger 2024 MD Anderson study of 1338 appendiceal adenocarcinoma patients found that elevation of any of the three markers was associated with significantly worse five-year survival, with the most striking gap seen in CA125 (69 percent vs 93 percent for elevated vs normal). A 2018 study from The Christie reached similar conclusions in a smaller CRS/HIPEC cohort.

What current guidelines say

The landscape is shifting. The 2025 NCCN Colon Cancer Guidelines (which currently house appendiceal adenocarcinoma recommendations) state that for appendiceal adenocarcinoma, CA-125 levels should be measured, particularly when CEA and CA19-9 are normal. They also note that normal CA-125 and CA19-9 levels correspond to better survival and lower recurrence.

Real-world adoption is uneven. Appendix cancer is rare. Many community oncologists see only a handful of cases. Lab systems may still flag CA125 as gynecologic. Universal surveillance protocols across institutions don’t yet exist.

Why this matters for men specifically

The concern isn’t theoretical. If a man’s disease primarily elevates CA125, while CEA and CA19-9 remain normal, not ordering CA125 could underestimate tumor burden, delay recognition of recurrence, and limit monitoring options during treatment. In a disease where peritoneal recurrence is hard to catch on imaging, a missed marker can mean a missed signal. We need every tool in our toolbelt even in none of the tests are 100%.

The bigger challenge in appendix cancer

Appendiceal adenocarcinoma often behaves differently from colorectal cancer. Peritoneal disease is difficult to measure on standard CT scans and difficult to quantify using RECIST criteria, which were designed for solid tumors that grow in measurable masses. That’s why tumor markers may carry more weight in appendix cancer than they do elsewhere. They’re often used for surveillance after CRS/HIPEC, for monitoring response to systemic chemotherapy, for estimating recurrence risk, and increasingly as endpoints in clinical trial design for a disease too rare to easily power large randomized studies.

The takeaway in one sentence

Emerging evidence suggests men with appendiceal adenocarcinoma may benefit from routine CA125 testing alongside CEA and CA19-9, but many hospitals still don’t consistently order it.

Questions to ask your care team

• Which tumor markers are being monitored in my case?
• Are all three (CEA, CA19-9, and CA125) being followed?
• If CA125 isn’t being ordered, why not?
• Which marker appears most informative for my disease?
• How often should tumor markers be checked after CRS/HIPEC?
• How are tumor markers being used alongside imaging in my surveillance plan?

Important limitations

These studies were retrospective and conducted largely at high-volume specialty centers. The field still needs prospective validation, standardized surveillance protocols, and broader multicenter data. Not every appendix cancer patient will have elevated tumor markers, and normal markers don’t rule out active disease. Tumor markers are one tool among several, not a standalone answer.

Glossary

CEA (Carcinoembryonic Antigen). A blood tumor marker commonly used in gastrointestinal cancers.

CA19-9. A tumor marker associated with some gastrointestinal cancers and peritoneal disease.

CA125. A tumor marker historically associated with ovarian cancer but increasingly recognized as relevant in appendiceal adenocarcinoma and peritoneal malignancies.

CRS/HIPEC. Cytoreductive surgery combined with heated chemotherapy delivered directly into the abdominal cavity.

Peritoneal disease. Cancer involving the lining of the abdominal cavity.

RECIST. Response Evaluation Criteria in Solid Tumors. The standard imaging-based system for measuring how much a tumor grows or shrinks during treatment, which works poorly for the diffuse peritoneal spread typical of appendix cancer.

Sources

• Aziz O. Measuring Triplet Perioperative Tumor Markers in Appendix Adenocarcinoma Regardless of Sex. JAMA Network Open. 2026;9(5):e2610578.
• Pattalachinti VK, et al. Appendiceal Adenocarcinoma Cytoreduction Outcomes and Perioperative Serum Tumor Marker Levels. JAMA Network Open. 2026;9(5):e2610569.
• Yousef A, et al. Serum Tumor Markers and Outcomes in Patients With Appendiceal Adenocarcinoma. JAMA Network Open. 2024;7(2):e240260.
• Aziz O, et al. Predicting Survival After CRS/HIPEC for Appendix Adenocarcinoma. Dis Colon Rectum. 2018;61(7):795-802.
• NCCN Clinical Practice Guidelines in Oncology: Colon Cancer, Version 4.2025.

Keep reading

What the NCCN Surveillance Guidelines Say About Appendix Cancer Follow-Up Tumor markers are one piece of a larger surveillance picture. Here’s what the current guidelines actually recommend for follow-up after appendix cancer treatment, including how often markers should be checked, when imaging is indicated, and what a rising number actually means.