CA-125
CA-125 is a protein produced by cells in the ovaries and pelvis. Testing is primarily used to monitor ovarian cancer treatment and detect recurrence — falling levels indicate treatment is working, rising levels may signal return of disease. Also helps evaluate pelvic masses, especially in postmenopausal women. Not recommended for routine screening in average-risk women because many benign conditions (endometriosis, fibroids, menstruation) also elevate CA-125.
CA-125 (Cancer Antigen 125) is a protein found on the surface of many cells, particularly ovarian cells. When these cells are irritated or damaged — whether by cancer or other conditions — CA-125 is released into the bloodstream. Elevated levels are associated with ovarian cancer, making CA-125 valuable for monitoring treatment and detecting recurrence.
However, CA-125 is not a simple “cancer yes or no” test. Many benign conditions also raise CA-125, including endometriosis, fibroids, pelvic inflammatory disease, and even normal menstruation. This limits its usefulness as a screening test for ovarian cancer in women without symptoms. Where CA-125 truly shines is in monitoring women already being treated for ovarian cancer — tracking whether treatment is working and detecting recurrence early.
Key Benefits of Testing
CA-125 testing serves several important purposes. For women with known ovarian cancer, it tracks treatment response — falling levels indicate treatment is working, while rising levels may signal recurrence. For women with pelvic masses, CA-125 helps assess whether a mass is more likely benign or malignant, guiding surgical planning.
In specific high-risk populations — particularly women with BRCA mutations or strong family history of ovarian cancer — CA-125 may be part of a surveillance strategy, though its role in screening remains limited by the many non-cancer causes of elevation.
What Does This Test Measure?
CA-125 measures the concentration of Cancer Antigen 125 protein in blood. This protein is produced by cells lining various body cavities including the ovaries, fallopian tubes, uterus, and peritoneum (abdominal lining). When these tissues are irritated, inflamed, or cancerous, more CA-125 enters the bloodstream.
Sources of CA-125
| Source | When CA-125 Rises | Clinical Context |
|---|---|---|
| Ovarian cancer | Cancer cells produce excess CA-125 | Primary use — monitoring treatment and recurrence |
| Endometriosis | Endometrial tissue outside uterus causes irritation | Common cause of elevated CA-125 in premenopausal women |
| Fibroids | Large fibroids can elevate levels | Benign, but can confuse interpretation |
| Pelvic inflammatory disease | Infection causes inflammation | Temporary elevation that resolves with treatment |
| Menstruation | Normal shedding of endometrium | Test ideally done after period ends |
| Pregnancy | Especially first trimester | Normal physiological elevation |
| Other cancers | Pancreatic, lung, breast, colon | Less specific than for ovarian cancer |
Why CA-125 Isn’t a Perfect Screening Test
For a screening test to work well, it needs to be elevated when cancer is present (sensitive) and normal when cancer is absent (specific). CA-125 falls short on both counts for general screening:
| Limitation | Explanation | Consequence |
|---|---|---|
| Not always elevated in early cancer | About 50% of early-stage ovarian cancers have normal CA-125 | Misses many cancers when they’re most treatable |
| Often elevated without cancer | Endometriosis, fibroids, PID, menstruation all raise it | False alarms leading to unnecessary worry and procedures |
| Ovarian cancer is relatively rare | Even a “good” test produces many false positives in rare diseases | Most women with elevated CA-125 don’t have ovarian cancer |
Why This Test Matters
Monitoring Ovarian Cancer Treatment
This is where CA-125 is most valuable. In women with ovarian cancer that produces CA-125 (not all do), the level serves as a real-time indicator of how well treatment is working:
- Falling CA-125 during chemotherapy — Treatment is working, cancer is responding
- CA-125 returns to normal — Good response, though doesn’t guarantee cure
- Rising CA-125 during or after treatment — Cancer may be progressing or recurring
Tracking CA-125 allows doctors to adjust treatment strategies and catch recurrence months before symptoms or imaging changes would appear.
Evaluating Pelvic Masses
When imaging discovers a pelvic mass, CA-125 helps assess the likelihood of malignancy:
| Patient Profile | CA-125 Result | Interpretation |
|---|---|---|
| Postmenopausal woman | Elevated | Higher concern for malignancy — referral to gynecologic oncologist |
| Postmenopausal woman | Normal | Lower concern, but doesn’t rule out cancer |
| Premenopausal woman | Elevated | May be endometriosis, fibroids, or other benign causes — context matters |
| Premenopausal woman | Normal | Benign cause more likely |
High-Risk Surveillance
Women at significantly increased risk for ovarian cancer — particularly those with BRCA1 or BRCA2 mutations — face difficult decisions about surveillance versus preventive surgery. While CA-125 combined with transvaginal ultrasound is sometimes used for monitoring, this approach has not been proven to reduce ovarian cancer deaths. Many high-risk women ultimately choose risk-reducing surgery (removal of ovaries and fallopian tubes) rather than ongoing surveillance.
Value of Testing When Evaluating Symptoms
Ovarian cancer is called “the silent killer” because early symptoms are vague — bloating, pelvic discomfort, feeling full quickly, urinary frequency. These symptoms are common and usually from benign causes. However, when symptoms are new, persistent (present most days for more than a few weeks), and represent a change from baseline, evaluation is warranted. CA-125, combined with pelvic examination and imaging, helps assess whether symptoms might represent something serious. Testing provides objective information that guides next steps — offering either reassurance or early detection of problems.
What Can Affect CA-125 Levels?
Conditions That Raise CA-125
Gynecologic conditions:
- Ovarian cancer (primary concern)
- Endometriosis (very common cause in premenopausal women)
- Uterine fibroids
- Pelvic inflammatory disease
- Ovarian cysts
- Adenomyosis
Other cancers:
- Fallopian tube cancer
- Primary peritoneal cancer
- Endometrial cancer
- Pancreatic, lung, breast, colon cancer (less consistently)
Non-gynecologic conditions:
- Liver cirrhosis
- Ascites (fluid in abdomen) from any cause
- Pleural effusion
- Heart failure
- Recent abdominal surgery
Normal physiological states:
- Menstruation
- Pregnancy (especially first trimester)
Testing Considerations
Timing: In premenopausal women, CA-125 can fluctuate with the menstrual cycle. Testing is ideally done after menstruation ends to avoid false elevation.
Trends matter: A single CA-125 value is less informative than the trend over time. Rising values are more concerning than a single elevated result that remains stable.
When Should You Get Tested?
Established Indications
- Monitoring known ovarian cancer — Track treatment response and detect recurrence
- Evaluating a pelvic mass — Help assess likelihood of malignancy, especially in postmenopausal women
- Persistent unexplained symptoms — New, persistent bloating, pelvic pain, difficulty eating, urinary symptoms warranting evaluation
Possible Indications (Discuss with Your Doctor)
- High-risk women (BRCA mutations, strong family history) — May be part of surveillance strategy, though limitations exist
- Monitoring endometriosis — Sometimes used to track disease activity
Not Recommended For
- Routine screening in average-risk women — Studies have not shown benefit, and false positives cause harm
- Annual “just to check” testing — Without symptoms or risk factors, not recommended
Understanding Your Results
Interpreting CA-125
Results are reported as units per milliliter (U/mL). The reference range typically considers values below a certain threshold as normal, but interpretation depends heavily on clinical context.
| Result Category | In Postmenopausal Women | In Premenopausal Women |
|---|---|---|
| Normal range | Reassuring but doesn’t exclude early cancer | Reassuring, cancer unlikely |
| Mildly elevated | Warrants further evaluation | Often benign (endometriosis, fibroids, etc.) |
| Moderately elevated | Concerning, imaging and possible referral needed | Context-dependent, may be benign or concerning |
| Highly elevated | High suspicion for malignancy | Concerning, needs evaluation |
Context Is Everything
The same CA-125 value can mean different things in different women:
- Mildly elevated in a 30-year-old with known endometriosis — likely related to endometriosis
- Mildly elevated in a 65-year-old with a pelvic mass — more concerning for malignancy
- Falling from high levels in a woman on chemotherapy — good treatment response
- Rising in a woman previously treated for ovarian cancer — possible recurrence
Trends Over Time
Serial measurements are often more informative than single values:
- Stable mildly elevated — Less concerning than rising values
- Steadily rising — Warrants investigation regardless of absolute level
- Falling during treatment — Positive response
- Rising after treatment — Possible recurrence, often detected months before symptoms
What to Do About Your Results
If CA-125 Is Normal
A normal result is reassuring but has limitations. About half of early-stage ovarian cancers don’t elevate CA-125. If concerning symptoms persist despite normal CA-125, further evaluation may still be warranted. Normal CA-125 in a woman being monitored after ovarian cancer treatment is a good sign.
If CA-125 Is Elevated
Don’t panic. Elevated CA-125 does not mean you have cancer. In premenopausal women especially, benign causes are far more common.
Next steps typically include:
- Review of symptoms and medical history
- Pelvic examination
- Pelvic ultrasound (transvaginal is most informative)
- Possibly repeat CA-125 to assess trend
- Referral to gynecologist or gynecologic oncologist depending on findings
If You’re Being Monitored for Ovarian Cancer
Your oncology team will interpret CA-125 trends in the context of your treatment. Generally:
- Falling levels — Continue current treatment approach
- Rising levels — May prompt imaging or treatment changes
- The trend and rate of change often matter more than absolute numbers
Related Health Conditions
Ovarian Cancer
Ovarian cancer is the most serious condition associated with elevated CA-125. Most cases are diagnosed at advanced stages because early symptoms are vague. CA-125 is primarily used for monitoring treatment response and detecting recurrence rather than initial screening. Treatment typically involves surgery and chemotherapy.
Endometriosis
Endometriosis occurs when tissue similar to the uterine lining grows outside the uterus. It commonly elevates CA-125, making interpretation challenging in premenopausal women. Symptoms include painful periods, pelvic pain, and infertility. CA-125 is sometimes used to monitor disease activity.
Ovarian Cysts
Most ovarian cysts are benign and resolve on their own. CA-125 helps assess whether a cyst is more likely benign or concerning for malignancy, particularly in postmenopausal women where benign functional cysts are less common.
Uterine Fibroids
Fibroids are benign uterine tumors that can elevate CA-125, especially when large. They cause symptoms like heavy bleeding and pelvic pressure but are not cancerous.
Pelvic Inflammatory Disease
PID is infection of the female reproductive organs, usually from sexually transmitted bacteria. It can significantly elevate CA-125. Levels return to normal after successful treatment.
Related Biomarkers Often Tested Together
HE4 (Human Epididymis Protein 4) — Another ovarian cancer marker, often combined with CA-125 in the ROMA score to better assess ovarian cancer risk in women with pelvic masses.
CEA (Carcinoembryonic Antigen) — Tumor marker that can help distinguish ovarian cancer type and detect other cancers that may spread to ovaries.
AFP (Alpha-Fetoprotein) — Elevated in certain ovarian germ cell tumors, useful in younger women with ovarian masses.
LDH (Lactate Dehydrogenase) — Non-specific marker that can be elevated in ovarian germ cell tumors.
Note: Information provided in this article is for educational purposes and doesn’t replace personalized medical advice.
Frequently Asked Questions
CA-125 is a protein found on the surface of many cells, particularly those in the ovaries and pelvis. When these cells are irritated — by cancer, endometriosis, infection, or other conditions — more CA-125 enters the bloodstream.
No. Most women with elevated CA-125 do not have ovarian cancer. Many benign conditions elevate CA-125, especially in premenopausal women. However, elevated CA-125 warrants evaluation to determine the cause.
For average-risk women without symptoms, CA-125 screening is not recommended. It hasn’t been shown to save lives and causes false alarms. For high-risk women (BRCA mutations, strong family history), discuss surveillance options with your doctor.
CA-125 can vary with menstrual cycle, pregnancy, and various benign conditions. This is why trends over time are more meaningful than single values, and why timing of testing matters.
About half of early-stage ovarian cancers don’t elevate CA-125. A normal result is reassuring but doesn’t completely exclude cancer. If you have persistent concerning symptoms, discuss further evaluation with your doctor.
CA-125 tracks how well treatment is working. Falling levels during chemotherapy indicate response. After treatment, regular CA-125 monitoring can detect recurrence months before symptoms appear, allowing earlier intervention.
References
Key Sources:
- American College of Obstetricians and Gynecologists. Practice Bulletin No. 174: Evaluation and Management of Adnexal Masses. Obstet Gynecol. 2016;128(5):e210-e226.
- US Preventive Services Task Force. Screening for Ovarian Cancer: Recommendation Statement. JAMA. 2018;319(6):588-594.
- National Comprehensive Cancer Network. NCCN Guidelines: Ovarian Cancer. 2024.