Monitoring and mass evaluation
CA-125 can help monitor treatment response, follow for recurrence, and evaluate a known pelvic mass. A trend over time can be more informative than one isolated value.
Evidence-led blood test guide
Blood Test for Ovarian Cancer
What CA-125, HE4 and ROMA can—and cannot—show, why routine screening is not recommended, and where Galleri fits.
Start with the direct answerHLI editorial team
Evidence reviewed by the editorial team. A named clinician has not been supplied; no medical reviewer is represented in the page schema.
The answer first
Can a Blood Test Detect Ovarian Cancer?
No single blood test can diagnose ovarian cancer. CA-125 is elevated in more than 80% of advanced cases but only about half of early-stage cases, and benign conditions can also raise it. Galleri® and other blood-based tests are being studied, but tissue examination is still required for diagnosis and no blood test is recommended for ovarian cancer screening.
Blood tests fall into three groups: single markers such as CA-125 and HE4; algorithms and panels such as ROMA, OVA1 and Overa; and cfDNA methylation tests such as Galleri and the research-stage OvaPrint. Each answers a different question, and all are adjuncts rather than standalone diagnostic tests.
Persistent bloating, pelvic or abdominal pain, feeling full quickly, or urinary urgency or frequency deserves medical evaluation. These symptoms commonly have benign causes, but routine bloodwork cannot rule ovarian cancer out.
The best-known marker
CA-125: What It Measures and Why It Falls Short
CA-125 is a glycoprotein shed by many epithelial ovarian cancers and some normal tissues. A common reference threshold is 35 U/mL, but the result must be interpreted with symptoms, menopausal status and imaging.
About half of Stage I cases
Roughly 50% of Stage I cancers have a normal CA-125. Some mucinous and clear-cell cancers do not raise it, and even advanced disease can occasionally produce a normal result.
Many benign conditions raise it
Endometriosis, fibroids, menstruation, pregnancy, liver disease and pelvic inflammation can increase CA-125. In premenopausal women, most elevated results arise from benign causes.
Not recommended for routine screening
CA-125 misses too many early cancers and produces too many false alarms. The American Cancer Society, USPSTF and other major organizations do not recommend it for population screening.
Why screening can cause harm
The USPSTF Recommendation: Why Ovarian Cancer Screening Hasn't Worked
USPSTF gives ovarian cancer screening a Grade D recommendation for average-risk, asymptomatic women. Trials of CA-125 and transvaginal ultrasound did not reduce deaths and led some women without cancer to undergo surgery and experience serious complications.
PLCO trial
CA-125 plus transvaginal ultrasound produced no mortality benefit. Among 3,285 women with false-positive results, 166 experienced a serious surgical complication—about 15% of those who underwent surgery after a false alarm.
UKCTOCS trial
Among 202,638 women followed for a median of 16 years, neither multimodal CA-125/ROCA screening nor ultrasound-only screening produced a statistically significant reduction in ovarian cancer mortality.
Scope matters
The Grade D recommendation addresses CA-125, transvaginal ultrasound and pelvic-exam screening. It does not evaluate Galleri or other multi-cancer early detection tests. That absence is not an endorsement. People with BRCA1/2 or Lynch syndrome are outside the average-risk recommendation and should receive genetic counseling and specialist guidance.
Triage tools, not screening tests
HE4 and ROMA: Other Blood Tests to Know
These tests help estimate malignancy risk after an adnexal or pelvic mass is already known. They can inform referral to a gynecologic oncologist; they are not intended to screen the general population.
A more specific protein marker
Human epididymis protein 4 has pooled sensitivity near 81% and specificity near 91% in meta-analysis. It is less commonly raised by endometriosis than CA-125, but kidney function and age affect interpretation.
CA-125 + HE4 + menopausal status
The Risk of Ovarian Malignancy Algorithm combines those inputs to classify a known mass as higher or lower risk. Published performance varies; one validation reported about 76.4% sensitivity at 95% specificity.
A five-protein panel
OVA1 is FDA-cleared for pre-surgical risk assessment. Its high sensitivity—reported near 97%—comes with lower specificity near 55%, so it is not a population screening test.
Second-generation mass assessment
Overa incorporates CA-125, HE4, FSH, apolipoprotein A-1 and transferrin. Cleared in 2016, it improved specificity over OVA1 while preserving a triage—not screening—role.
A 60-point survival gap
Why Early Detection Matters So Much for Ovarian Cancer
Five-year relative survival is 92% for localized disease and 32% for distant disease. Yet only 22% of cases are diagnosed while localized; 54% are diagnosed after distant spread.
The American Cancer Society estimated about 21,010 US diagnoses and 12,450 deaths in 2026. The survival gap explains the urgency around new tests, but it does not prove that finding a signal earlier will reduce mortality. A screening test must demonstrate benefits that outweigh false positives, overdiagnosis and follow-up harms.
A different signal and a broader purpose
Galleri: Multi-Cancer Detection Including Ovarian Cancer
Galleri analyzes cell-free DNA methylation patterns and predicts a likely signal origin. GRAIL includes ovary among its 12 pre-specified cancers. It is under FDA review and has not been approved or cleared by the FDA.
83.1%Ovarian sensitivity in secondary-sourced CCGA3 case-control data—not a prospective estimate
50.0%Stage I sensitivity in the same case-control dataset; half were missed
69.8%Prospective PATHFINDER 2 sensitivity for the 12 cancers together—not ovary alone
Case-control limits: CCGA3 studied people already known to have cancer, a design that can overstate screening performance. The ovarian values—50.0% Stage I, 80.0% Stage II, 87.1% Stage III, 94.7% Stage IV and 83.1% overall—are secondary-sourced from citations to Klein et al. and require primary-figure verification.
Prospective evidence: PATHFINDER 2 included 35,878 adults without clinical suspicion of cancer. Across the 12 pre-specified cancers, sensitivity was 69.8%, specificity 99.6%, positive predictive value 60.3% and signal-origin accuracy 91.3%. No ovary-only prospective estimate has been verified.
Stage I limitation: In the case-control dataset, Galleri missed half of Stage I ovarian cancers. That is similar to the approximate Stage I sensitivity of CA-125 reported in separate literature, but the tests have not been compared head to head.
NHS-Galleri context: Results were mixed. The trial did not meet its primary endpoint of reducing combined Stage III–IV diagnoses across the 12 cancers, although Stage IV diagnoses fell by more than 20% in rounds two and three.
Galleri's broader multi-cancer purpose, prospective specificity and CA-125's ovarian workup role come from different studies and populations. No claim of superiority can be made from these data. Review the wider Galleri evidence and limitations and current FDA status.
Not a head-to-head comparison
Galleri vs CA-125: Different Tests for Different Purposes
CA-125 supports evaluation and monitoring for ovarian cancer. Galleri screens for a signal shared by many cancers in eligible adults. The figures below come from different study designs.
| Question | CA-125 | Galleri |
|---|---|---|
| What it detects | CA-125 protein level | Cancer-associated cfDNA methylation patterns |
| Primary purpose | Monitoring treatment or recurrence; evaluating a known pelvic mass | Multi-cancer screening in adults with elevated cancer risk |
| Ovarian sensitivity | About 50% Stage I; about 90% in more advanced disease | 83.1% overall and 50% Stage I in case-control data; secondary-sourced |
| Specificity | Limited for screening because many benign conditions raise it | 99.6% across cancers in PATHFINDER 2; no direct comparison with CA-125 |
| Guideline status | USPSTF Grade D against population screening | Not evaluated by USPSTF; no ACS or NCCN endorsement |
| Regulatory status | Established clinical marker | Laboratory-developed test under FDA review; not approved or cleared |
| Cost through HLI | Included in our annual blood panel | $798; prescription required; not covered by Medicare |
The ovarian percentages are not evidence that Galleri outperforms CA-125. They were produced in separate studies with different populations, endpoints and methods.
Inherited risk changes prevention
Who Is at Highest Risk for Ovarian Cancer?
BRCA1 carriers have an estimated 39–63% lifetime ovarian cancer risk; BRCA2 carriers have an estimated 16.5–27% risk. Lynch syndrome and pathogenic variants in genes such as BRIP1, RAD51C and RAD51D can also increase risk.
- Risk-reducing surgery: bilateral salpingo-oophorectomy after childbearing is the primary prevention strategy for many high-risk carriers. Timing is individualized; guidelines generally discuss ages 35–40 for BRCA1 and 40–45 for BRCA2.
- Surveillance gap: CA-125 and transvaginal ultrasound may sometimes be offered, but no surveillance approach has shown a mortality benefit even in high-risk populations.
- Residual risk: a small risk of primary peritoneal cancer remains after risk-reducing surgery.
- Galleri's role: Galleri does not replace genetic counseling, specialist surveillance, or risk-reducing surgery.
BRCA1, BRCA2 and inherited ovarian cancer risk Lynch syndrome and ovarian cancer risk See what the $599 genome service includes
Predisposition is not detection
Whole genome sequencing may identify inherited risk; it does not detect an existing ovarian cancer. Most ovarian cancers occur without a known high-risk variant, so a negative inherited-risk result does not rule out disease.
The diagnosis requires tissue
How Ovarian Cancer Is Actually Diagnosed
A definitive diagnosis requires pathology. Blood tests, risk algorithms and imaging can raise or lower suspicion, but ovarian cancer is confirmed by examining tissue obtained during surgery or, in selected cases, cells from fluid.
Evaluation often begins with pelvic examination and transvaginal ultrasound. CT imaging helps assess spread and plan care. When cancer is suspected, referral to a gynecologic oncologist before surgery improves the chance that staging and tumor removal are performed together.
After diagnosis, tumor testing may include BRCA1/2, homologous recombination deficiency, mismatch repair or microsatellite instability, and other biomarkers that can inform treatment. These tests guide therapy; they do not replace tissue diagnosis.
Clear answers
Frequently Asked Questions
Can ovarian cancer be detected by a routine blood test?
Not reliably. A CBC or comprehensive metabolic panel does not screen for ovarian cancer. CA-125 is not recommended for routine screening because benign conditions can raise it and about half of Stage I cancers do not raise it. Galleri can flag some ovarian cancer signals, but it is under FDA review and is not diagnostic.
What blood markers are high with ovarian cancer?
CA-125 is elevated in more than 80% of advanced epithelial ovarian cancers and about 50% of early-stage cases. HE4 is another epithelial cancer marker. AFP, beta-hCG and LDH can be relevant to germ-cell tumors, while inhibin A and B can be relevant to granulosa-cell tumors.
Why would a doctor order a CA-125 blood test?
Doctors use CA-125 to evaluate a pelvic mass alongside imaging, monitor response to treatment, and look for recurrence after treatment. An elevated result is not a diagnosis, and a normal result does not rule ovarian cancer out.
Is there a screening test for ovarian cancer?
No ovarian-specific screening test is recommended for average-risk, asymptomatic women. USPSTF recommends against CA-125 and transvaginal ultrasound screening because trials found no mortality benefit and meaningful harm from false-positive surgery. Multi-cancer tests remain under study.
What is OvaPrint?
OvaPrint is a research-stage cfDNA methylation test developed to distinguish high-grade serous ovarian cancer from benign pelvic masses. A validation study reported 84.2% sensitivity and 96.0% specificity. It is not commercially available for routine population screening.
Sources and Evidence Notes
Key sources: USPSTF, JAMA (2018, Grade D recommendation); Buys et al., JAMA (2011, PLCO); Menon et al., Lancet (2021, UKCTOCS); SEER Cancer Stat Facts and American Cancer Society Cancer Facts & Figures 2026; Ferraro et al., Clinical Chemistry and Laboratory Medicine (HE4); Moore et al., Gynecologic Oncology (ROMA); Klein et al., Annals of Oncology (2021, CCGA3 case-control); Salhia et al., Clinical Cancer Research (2023, OvaPrint); Schrag et al., Lancet (2023, PATHFINDER); GRAIL PATHFINDER 2 and NHS-Galleri releases (2026); and FDA advisory materials (September 2026). CCGA3 ovarian stage figures are secondary-sourced and should be checked against the primary figure before publication.