What is the significance of elevated Carcinoembryonic Antigen (CEA) and Cancer Antigen 125 (CA 125) in a male patient with peritoneal carcinomatosis of unknown primary source and a liver lesion?

From the Guidelines

Elevated CEA and CA 125 levels in the 300s range in a male patient with peritoneal carcinomatosis and a liver lesion strongly suggest a gastrointestinal or hepatobiliary malignancy, most likely colorectal or pancreatic cancer with metastasis. This combination of tumor markers is particularly concerning as CEA is associated with colorectal, gastric, and pancreatic cancers, while CA 125, though typically linked to ovarian cancer, can also elevate in gastrointestinal malignancies with peritoneal involvement, as noted in studies such as 1. Immediate comprehensive evaluation is essential, including:

• A full-body CT scan with contrast to assess the extent of disease
• Colonoscopy and upper endoscopy to evaluate for primary gastrointestinal tumors
• Biopsy of accessible lesions for histopathological confirmation and immunohistochemical analysis
• PET-CT to help identify the primary tumor site, as recommended in guidelines such as 1 for cases where radical locoregional treatment is considered Tissue samples should undergo molecular profiling for targetable mutations and microsatellite instability status to guide treatment decisions, considering the latest recommendations for cancer of unknown primary, as outlined in 1 and 1. While awaiting definitive diagnosis, consultation with both medical and surgical oncology is recommended to develop a multidisciplinary treatment plan, which may include systemic chemotherapy (such as FOLFOX or FOLFIRI regimens for suspected colorectal origin) and evaluation for potential cytoreductive surgery with HIPEC if appropriate, based on guidelines such as 1 that emphasize the role of CEA in monitoring and prognosis. The elevated tumor markers not only suggest diagnosis but will serve as valuable monitoring tools during treatment to assess response, as highlighted in studies focusing on the utility of tumor markers in gastrointestinal cancers, including 1.

From the Research

Significance of Elevated CEA and CA 125

• Elevated CEA and CA 125 in the 300s range for a patient with peritoneal carcinomatosis of unknown source and liver lesion in a male patient may indicate a poor prognosis 2, 3.
• A study found that an elevated CA125 was independently associated with reduced overall survival in patients with peritoneal metastases 2.
• Another study found that CA125 concentration was a better tumor marker than CEA for predicting peritoneal dissemination of colorectal cancer in both men and women 3.
• However, a study on patients with primary appendiceal adenocarcinoma found that CA-125 was not predictive of progression-free survival or overall survival 4.

Diagnostic Accuracy

• The diagnostic accuracy of FDG PET or PET/CT in detecting peritoneal carcinomatosis was found to be 87.8% 5.
• However, the extent of peritoneal carcinomatosis was understaged with CT and PET/CT in 27 patients and overstaged in 1 and 2 patients, respectively 6.
• The interclass correlation was moderate between CT and surgery, but low between PET/CT and surgery 6.

Tumor Markers

• Elevated preoperative CA19-9 portends worse progression-free survival, while elevated CEA predicts worse overall survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) in patients with primary mucinous adenocarcinoma of the appendix 4.
• Tumor differentiation was the most potent predictor of both progression-free survival and overall survival 4.
• The coexistence of CEA elevation and unfavorable histology led to the lowest survival rate at two years 4.