Which tumors are associated with elevated CA‑125 levels?

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CA-125 Elevation: Malignant and Benign Tumors

CA-125 is most consistently elevated in epithelial ovarian cancer (particularly high-grade serous carcinoma, present in ~85% of advanced disease), but can also be elevated in endometrial cancer, fallopian tube cancer, primary peritoneal cancer, and several non-gynecologic malignancies including colorectal, breast, pancreatic, colon, and lung cancers. 1, 2

Primary Gynecologic Malignancies

Ovarian Cancer

  • High-grade serous carcinoma accounts for 70% of epithelial ovarian cancer cases and shows the most reliable CA-125 elevation 1
  • CA-125 is elevated in approximately 85% of advanced-stage ovarian cancer but only 50% of early-stage (FIGO I) disease, making it a poor screening tool 1
  • Other epithelial subtypes include endometrioid carcinoma (10%), clear cell carcinoma (6-10%), low-grade serous carcinoma (5%), and mucinous carcinoma (3-4%) 1
  • CA-125 is NOT a reliable marker in non-high-grade serous ovarian cancers, particularly mucinous, clear cell, endometrioid, and low-grade serous types 1

Other Gynecologic Cancers

  • Endometrial cancer: More than half of patients with advanced-stage or high-grade disease have elevated pretreatment CA-125 levels 1
  • CA-125 should be considered in select endometrial cancer patients with advanced disease, serous histology, or elevated pretreatment levels 1
  • Fallopian tube cancer and primary peritoneal cancer are managed similarly to epithelial ovarian cancer and show comparable CA-125 elevation patterns 3

Non-Gynecologic Malignancies

  • Colorectal cancer and breast cancer can have elevated CA-125 levels 1
  • Pancreatic, colon, and lung cancers may also express CA-125 2
  • When evaluating elevated CA-125 with a pelvic mass, measure CEA and CA 19-9 in addition to CA-125 to distinguish primary ovarian tumors from gastrointestinal metastases 1
  • A CA-125/CEA ratio >25 favors ovarian origin over gastrointestinal origin 1
  • A CA-125/CEA ratio <25:1 should raise suspicion for a GI primary, especially with family history of colorectal cancer 1

Benign Conditions with Elevated CA-125

Gynecologic Benign Conditions

  • Endometriosis can cause marked CA-125 elevation, even exceeding 1,000 U/mL 4, 5
  • Adenomyosis (particularly cystic adenomyosis) can produce very high CA-125 levels 4
  • Pelvic inflammatory disease 1
  • Ovarian cysts (benign serous cystadenomas can have cyst fluid CA-125 up to 371,000 U/mL, though serum levels typically remain normal due to intact basement membrane barrier) 6
  • Menstruation and pregnancy 7

Non-Gynecologic Benign Conditions

  • Cirrhosis with ascites universally elevates CA-125 because mesothelial cells under pressure from fluid produce the antigen 1
  • Heart failure 1
  • Renal failure and hepatitis 1
  • Peritonitis and diseases leading to pleural effusion or ascites 5
  • Previous radiotherapy may cause elevated CA-125 levels 1

Critical Clinical Limitations

  • CA-125 has limited specificity and should never be used alone for diagnosis or treatment decisions 1
  • Marked increases in CA-125 of >1,000 U/mL and even up to 5,000 U/mL can occur in benign conditions 5
  • The American College of Radiology recommends against using CA-125 alone to make surgical decisions 1
  • Do not test serum CA-125 in patients with ascites of any cause, as it is universally elevated and nonspecific 1
  • CA-125 performs worse than ultrasound alone in distinguishing benign from malignant ovarian lesions 8
  • Ultrasound-based diagnostic models (IOTA Simple Rules or IOTA ADNEX model) are superior to CA-125 alone 1

Appropriate Clinical Use

  • Monitoring disease response to treatment and detecting recurrence in patients with established epithelial ovarian cancer (sensitivity 62-74% for recurrence detection) 1
  • Serial CA-125 measurements require two elevated values at least one week apart to confirm progression 1
  • Rising CA-125 in asymptomatic patients after treatment typically precedes clinical relapse by 2-6 months 1
  • CA-125 aids diagnosis when interpreted alongside imaging and clinical findings, not as a standalone test 1

References

1
Guideline

Cancers Associated with Elevated CA-125 Levels

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

2
Research

CA 125: the past and the future.

The International journal of biological markers, 1998

3
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

7
Research

The CA 125 tumour-associated antigen: a review of the literature.

Human reproduction (Oxford, England), 1989

8
Guideline

Diagnostic Approach for Hemorrhagic or Complex Ovarian Cysts

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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