CA125:CEA Ratio Interpretation in Postmenopausal Women with Adnexal Masses
A high CA125:CEA ratio (typically when CA125 is elevated and CEA remains low or normal) strongly suggests an ovarian primary malignancy rather than a gastrointestinal primary tumor, optimizing specificity for distinguishing between these two cancer origins. 1
Primary Clinical Application
The CA125:CEA ratio serves a specific diagnostic purpose when evaluating adnexal masses:
The ratio is used to differentiate ovarian epithelial neoplasms from gastrointestinal primary cancers that have metastasized to the ovaries, as both can present with elevated tumor markers and pelvic masses. 1
A high CA125:CEA ratio indicates ovarian origin, while a low ratio (elevated CEA with normal or minimally elevated CA125) suggests gastrointestinal malignancy. 1
Understanding the Individual Markers
CA125 Performance Characteristics
CA125 has 98.5% specificity in postmenopausal women when using the standard 35 U/mL threshold, making it highly reliable when elevated in this population. 2
Sensitivity is only 50% for stage I ovarian cancer, meaning normal levels do not exclude early malignancy. 1, 3
CA125 detects 80-90% of serous carcinomas (the most common epithelial ovarian cancer type) but only 15 of 17 mucinous ovarian carcinomas in one study. 3, 4
CEA Performance Characteristics
CEA is elevated in 15 of 17 patients with mucinous ovarian cancer in published series, demonstrating particular utility for this histologic subtype. 4
CEA elevation with adnexal masses should raise suspicion for gastrointestinal primary malignancy or mucinous ovarian tumors rather than typical serous ovarian cancer. 1, 4
Practical Interpretation Algorithm
When both markers are measured in a postmenopausal woman with an adnexal mass:
High CA125 (>35 U/mL) + Normal CEA (<5.0 μg/L) = High ratio → Strongly suggests ovarian primary malignancy, particularly serous histology. 1, 4
Normal CA125 + Elevated CEA → Consider gastrointestinal primary with ovarian metastases or mucinous ovarian tumor. 1, 4
Both elevated → The ratio calculation becomes critical; higher CA125 relative to CEA still favors ovarian origin. 1
Both normal → Does not exclude malignancy, particularly early-stage or borderline tumors; imaging features take precedence. 2, 3
Clinical Context and Limitations
When This Ratio Adds Value
The parallel combination of CA125 and CEA assays is more sensitive (90% positive predictive value) than CA125 alone for detecting malignancy in adnexal masses. 4
The ratio optimizes specificity specifically for distinguishing ovarian versus gastrointestinal primary neoplasms, which is clinically relevant when imaging shows features that could represent either entity. 1
Critical Pitfalls to Avoid
Never rely on tumor markers alone without correlating with imaging findings, as ultrasound morphology is superior to CA125 in distinguishing benign from malignant lesions. 2, 3
CA125 is frequently elevated in benign conditions including endometriosis, pelvic inflammatory disease, and benign cysts, which can cause false-positive results and misleading ratios. 2, 3
The ratio does not help differentiate benign from malignant ovarian masses—its specific utility is distinguishing ovarian primary from metastatic gastrointestinal cancer. 1
Integration with Imaging
Ultrasound morphology takes precedence over tumor marker levels in determining management, and suspicious imaging features warrant referral even with normal markers. 5
Color Doppler should be included to assess vascularity patterns and differentiate solid components from debris. 2, 5
MRI with IV contrast is the next step for masses that remain indeterminate after ultrasound evaluation, not additional tumor marker testing. 2, 3