OncoFirm™ / Cancer Atlas 2026 / Ovarian cancer

Cancer Atlas 2026 · Ovarian cancer

Ovarian Cancer Biomarkers in 2026: CA-125, HE4, the UKCTOCS Lesson and Why No Screening Is Recommended

Ovarian cancer is uncommon but often fatal, because more than half of cases are found after the cancer has spread. No screening test is recommended, and the largest trial of CA-125 screening found earlier-stage cancers without saving lives. This Atlas chapter explains what biomarkers do today, what failed, and what research is testing, using sources dated to 1 October 2026.

By OncoFirm™ Scientific TeamPublished 1 Oct 2026Updated 1 Oct 2026Sources peer-reviewed, guidelines, regulators, linked

At a glance

Global burden, 2024

About 331,000 new cases and 204,000 deaths (GLOBOCAN 2024)

US 5-year survival

52.0% overall: 91.9% localized, 31.5% distant (SEER, 2016–2022)

Screening

Not recommended for women without symptoms at average risk (USPSTF Grade D)

Key biomarkers

CA-125 and HE4 for mass triage and monitoring; BRCA1/2, HRD, FRα and PD-L1 for therapy

OncoFirm™ status

Assays in development; research use only; no ovarian cancer test or claim

On this page

Key numbers

Ovarian cancer in three numbers

54%of US cases are diagnosed at distant stage
91.9%5-year relative survival at localized stage (US)
31.5%5-year relative survival at distant stage (US)

Source: SEER Cancer Stat Facts: Ovarian Cancer (cases diagnosed 2016–2022).

Burden

Less common than breast cancer, far more lethal per case

The GLOBOCAN 2024 estimates count 330,731 new ovarian cancers worldwide in 2024 (1.6% of all cancers, ranked 18th by cases) and 203,850 deaths. In the United States, 21,010 new cases and 12,450 deaths are estimated for 2026. This chapter is part of the OncoFirm™ Cancer Atlas 2026.

A crude ratio of same-year deaths to new cases is about 0.62 worldwide and about 0.59 in the US. For breast cancer the same ratios are about 0.29 and 0.13. These are not survival statistics. Still, the near-equal global and US figures are consistent with the lack of an effective early-detection method anywhere.

There is progress. The US death rate has fallen 45% since 1976, by 2% to 3% per year from 2003 through 2023. Gaps remain: 5-year relative survival is 44% in Black women and 60% in Asian American and Pacific Islander women.

Why stage matters

Most cases are found late

Ovarian cancer: five-year relative survival by stage at diagnosisBar chart of five-year relative survival for Ovarian cancer by stage at diagnosis in the United States, 2016–2022: Localized 91.9% survival, 22% of cases; Regional 70.1% survival, 18% of cases; Distant 31.5% survival, 54% of cases. All stages combined: 52.0%. Source: SEER Cancer Stat Facts.OVARIAN CANCER · FIVE-YEAR RELATIVE SURVIVAL BY STAGE (US, 2016–2022)0%25%50%75%100%Localized22% of cases91.9%Regional18% of cases70.1%Distant54% of cases31.5%All stages combined: 52.0% · SEER Cancer Stat Facts

Five-year relative survival by stage at diagnosis for ovarian cancer, with the share of cases found at each stage. US cases diagnosed 2016–2022. Source: SEER Cancer Stat Facts: Ovarian Cancer (National Cancer Institute).

The chart uses US SEER registry data for cases diagnosed from 2016 to 2022. Relative survival compares people who have a cancer with the general population. Five-year relative survival is 52.0% overall: 91.9% for localized disease, 70.1% for regional disease and 31.5% for distant disease. The problem is the stage mix. Only 22% of cases are found while localized and 18% at regional stage. More than half, 54%, are distant at diagnosis.

Read the chart with care. High survival at localized stage does not prove that screening would save lives. Localized ovarian cancers are more often slower-growing types. High-grade serous carcinoma (HGSC), the type behind 95% of deaths in the largest screening trial, has only a short early-stage window. For the general case, see why early detection matters.

Screening

Screening: why no test is recommended

The US Preventive Services Task Force (USPSTF) recommends against screening for ovarian cancer in women without symptoms who are not known to have a high-risk hereditary cancer syndrome. This Grade D recommendation dates from 13 February 2018 and is current as of 1 October 2026. The American Cancer Society states that there are no recommended screening tests. The key evidence is UKCTOCS, a UK trial of yearly CA-125 testing:

  1. Design: about 200,000 average-risk women aged 50 to 74 were assigned to yearly multimodal screening (CA-125 read by a risk algorithm, with ultrasound as a second test), yearly transvaginal ultrasound, or no screening.
  2. Follow-up: a median of 16.3 years, reported in The Lancet in 2021.
  3. Stage shift: with multimodal screening, 47% more women were diagnosed at stage I and 25% fewer at stage IV.
  4. Deaths: 0.58% of women died of ovarian cancer with multimodal screening and 0.61% without screening (P = 0.58). Neither strategy reduced mortality.

A 2026 analysis in the British Journal of Cancer suggests why. HGSC made up 95% of advanced-stage cancers and 95% of deaths in the trial. The model estimates that HGSC can be detected at an early stage for less than 6 months. Continued screening with current tests would cut deaths by 15% at most. A cut of 20% or more would need a detection window of 1 year and at least 70% sensitivity.

Screening also causes harm. In the trials reviewed by USPSTF, false-positive rates ranged from 4.2% to 44.2% depending on the test. Between 0.2% and 3.25% of screened women without cancer had surgery, and up to 15% of those had major complications. The US PLCO trial of CA-125 plus ultrasound also found no mortality benefit. CA-125 detects only about 56% of stage I and II cancers at a cut-point set for 95% specificity.

The UKCTOCS lesson. A biomarker program can find cancers at an earlier stage and still fail to reduce deaths. Any new ovarian test has to clear that bar. More examples are in the early detection evidence hub.

Biomarkers

Established biomarkers by role

Ovarian biomarkers fall into two groups. Serum markers help assess a woman who already has an adnexal mass (a growth beside the uterus, usually on an ovary or fallopian tube) and track treated disease. Tissue and inherited (germline) markers select therapy. Roles are defined in Cancer biomarkers explained.

BiomarkerTypeUsed forNot used for
CA-125 (serum)Diagnostic aid, monitoringHelping assess a pelvic mass; tracking treatment response and recurrenceScreening women without symptoms
HE4 (serum)Triage, monitoringCombined with CA-125 in ROMA; monitoring progression and recurrenceScreening
ROMA, OVA1, Overa (serum panels)TriageEstimating the chance of cancer in a woman with an adnexal mass planned for surgeryScreening; stand-alone diagnosis
BRCA1/2 (germline or tumor)PredictiveSelecting PARP inhibitors such as olaparib and rucaparibDetecting a cancer
HRD (tissue)PredictiveOlaparib eligibilityScreening
Folate receptor alpha (tissue)PredictiveSelecting mirvetuximab soravtansine in platinum-resistant diseaseScreening
PD-L1 (tissue)PredictivePembrolizumab with paclitaxel in platinum-resistant diseaseScreening

Serum panels trade specificity for sensitivity. A March 2026 medical policy review lists sensitivity and specificity of 92% and 42% for OVA1, 90% and 67% for ROMA (FDA cleared in 2011), and 94% and 65% for Overa (FDA cleared in 2016). That profile can support a referral decision before surgery. It is unusable for screening, where low specificity leads to unnecessary operations. The same review notes FDA boxed warnings against use for screening, and that NCCN does not recommend these tests to decide the management of an undiagnosed mass.

Therapy selection has grown. ASCO advises germline BRCA1/2 testing for all women with epithelial ovarian cancer; in 2020 only about 30% were being tested. HRD (homologous recombination deficiency) means a tumor cannot repair DNA properly, and an FDA companion diagnostic uses it to select olaparib. Folate receptor alpha (FRα) staining selects mirvetuximab soravtansine, fully approved on 22 March 2024 after overall survival of 16.5 versus 12.7 months in the MIRASOL trial. On 10 February 2026 the FDA approved pembrolizumab with paclitaxel for PD-L1-positive, platinum-resistant disease. Overall survival was 18.2 versus 14.0 months in KEYNOTE-B96.

Serum markers and antigens

CA-125, MUC16 and glycan antigens: established versus research

Established. CA-125 is an epitope (an antibody-binding site) on MUC16, a large mucin, a protein coated in sugar chains called glycans. A 2024 paper counts 249 potential N-glycosylation sites and more than 3,700 O-glycosylation sites on its outer domain. CA-125 and HE4 are the only serum proteins here with an established clinical role, and that role is triage and monitoring. CA-125 is a tumor-associated antigen: it is not unique to cancer, which limits specificity.

Research stage. Tumors can display shortened glycans such as sialyl-Tn (STn), Tn and the Thomsen-Friedenreich (TF) antigen. A 2024 study measured free STn in serum with a custom assay. It separated malignant from benign cases with 15.3% sensitivity at 97.1% specificity and did not outperform CA-125 in serous cancers. Researchers are now testing CA-125 glycoforms, such as STn carried on MUC16, to tell cancer from benign causes like endometriosis. An approved NCI data-access project is titled “Glycovariants of CA-125 for early detection of ovarian cancer.” An antibody-drug conjugate against STn is preclinical.

Limits. These glycoform assays are research-stage. We found no FDA-cleared or guideline-endorsed glycoform test for ovarian cancer, and their value is unproven in prospective screening cohorts. We found no reliable data on a TF-based ovarian cancer test.

Emerging

Emerging approaches in 2025–2026

  • Multi-cancer early detection (MCED): in a case-control study, the Galleri blood test, which reads methylation patterns on cell-free DNA, detected 83.1% of ovarian cancers across all stages combined (51.5% for all cancers). This is not screening performance: stage I sensitivity was not available in the sources we read.
  • NHS-Galleri: this randomized trial of 142,942 adults counted ovarian cancer among its 12 prespecified cancers. It missed its primary endpoint, a reduction in stage III and IV diagnoses (incidence rate ratio 1.03). Stage IV diagnoses were 14% lower overall. No ovarian-specific result was reported, and the effect on deaths is unknown.
  • Regulatory status: no MCED test is FDA approved as of 1 October 2026. An FDA advisory panel backed Galleri on 23 September 2026, and the decision is pending.
  • Single-cancer tests: OvaPrint, a cell-free DNA methylation test for HGSC in women with a pelvic mass, reported 91% accuracy in a development study of more than 370 samples. Its developers say it needs validation in hundreds of patients before clinical use.

Other research combines DNA and protein signals, an approach covered in Multi-biomarker analysis and Emerging cancer diagnostic technologies. For background, see liquid biopsy explained. The pattern matches UKCTOCS: a shift in stage is achievable, but no ovarian early-detection approach has yet shown fewer deaths.

Open questions

Open research questions

  • Can any blood signal (methylated DNA, CA-125 glycoforms, protein panels) find HGSC about a year before it would otherwise appear, with at least 70% sensitivity?
  • Can markers with better specificity shorten the time to diagnosis in women with symptoms, even if population screening fails?
  • Will the stage IV reduction seen in NHS-Galleri translate into fewer deaths? Follow-up continues.
  • How should BRCA, HRD, FRα and PD-L1 testing be sequenced when tissue is limited, and how can genetic testing reach more patients?
  • Why do survival gaps between racial and ethnic groups persist?

OncoFirm™ roadmap

Where OncoFirm™ fits, and where it does not

OncoFirm™ is developing quantitative fluorescent lateral flow assays with a digital reader. They are in development, not cleared or approved by the FDA or any other regulatory authority, for research use only and not for sale. OncoFirm™ has no ovarian cancer assay and makes no screening claim.

No ovarian assay

The assays in development measure CEA (designed range 1–100 ng/mL) and PSA (0.5–50 ng/mL). Neither is an ovarian cancer marker.

Quantitative reader

The digital reader is designed to give a numeric result in 20 minutes or less. That is a development target, not validated performance.

TF antigen concepts

Assay concepts for the TF antigen, which use peanut agglutinin as a binding lectin, are concept-stage. No TF-based ovarian test is validated.

The bar set by UKCTOCS

Serial CA-125 with a risk algorithm did not reduce deaths. Any future research must be judged on outcomes, not sensitivity alone. See clinical collaborations.

OncoFirm™ assays, reader and software are in development, have not been cleared or approved by the FDA or any other regulatory authority, are for research use only and are not for sale. Designed ranges and result times are development targets, not validated performance claims.

FAQ

Frequently asked questions

Is there a screening test for ovarian cancer?

No. As of 1 October 2026, no organization recommends screening women without symptoms who are at average risk. USPSTF recommends against it (Grade D), because trials of CA-125 and ultrasound did not reduce deaths and false positives led to unnecessary surgery.

What did the UKCTOCS trial show?

UKCTOCS followed about 200,000 women for a median of 16.3 years. Yearly CA-125 screening with a risk algorithm found 47% more stage I cancers and 25% fewer stage IV cancers, but ovarian cancer deaths were not reduced. It shows that finding cancer earlier does not always save lives.

What is CA-125 used for?

CA-125 is a blood marker used to help assess a pelvic mass and to follow response to treatment and recurrence. It is not a screening test. At a cut-point set for 95% specificity, it detects only about 56% of stage I and II ovarian cancers.

What are ROMA and OVA1?

They are blood test panels that combine CA-125 with other proteins to estimate the chance that an adnexal mass is cancer before planned surgery. They are sensitive but not very specific. FDA boxed warnings say they should not be used for screening or as stand-alone diagnostic tests.

Which biomarkers guide ovarian cancer treatment?

BRCA1/2 mutations and HRD status select PARP inhibitors. Folate receptor alpha staining selects mirvetuximab soravtansine. Since February 2026, PD-L1 staining selects pembrolizumab with paclitaxel in platinum-resistant disease.

Can a multi-cancer blood test find ovarian cancer early?

Not proven. One test detected 83.1% of ovarian cancers in a case-control study that combined all stages, but the randomized NHS-Galleri trial missed its primary endpoint and reported no ovarian-specific result. No multi-cancer test is FDA approved as of 1 October 2026.

Does OncoFirm™ offer an ovarian cancer test?

No. OncoFirm™ assays, reader and software are in development, are not cleared or approved by the FDA or any other regulatory authority, are for research use only and are not for sale. OncoFirm™ has no ovarian cancer assay and makes no screening claim.

Sources

References

  1. International Agency for Research on Cancer. Global Cancer Observatory: World fact sheet, GLOBOCAN 2024. gco.iarc.who.int/media/globocan/factsheets/populations/900-world-fact-sheet.pdf
  2. Sung et al. Global cancer statistics 2024: GLOBOCAN estimates of incidence and mortality worldwide for 34 cancers in 186 countries. CA: A Cancer Journal for Clinicians. 2026. DOI 10.3322/caac.70090. acsjournals.onlinelibrary.wiley.com/doi/10.3322/caac.70090
  3. American Cancer Society. Cancer Facts & Figures 2026. www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2026/2026-cancer-facts-and-figures.pdf
  4. National Cancer Institute. SEER Cancer Stat Facts: Ovarian Cancer (read 1 October 2026). seer.cancer.gov/statfacts/html/ovary.html
  5. US Preventive Services Task Force. Ovarian Cancer: Screening. Final recommendation statement, 13 February 2018. www.uspreventiveservicestaskforce.org/uspstf/recommendation/ovarian-cancer-screening
  6. Menon et al. UKCTOCS long-term ovarian cancer mortality results. The Lancet. 2021;397(10290):2182–2193. www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00731-5/fulltext
  7. American Academy of Family Physicians. Summary of Menon et al., UKCTOCS. American Family Physician. October 2021. www.aafp.org/afp/2021/1000/p422a
  8. National Cancer Institute. Ovarian, Fallopian Tube, and Primary Peritoneal Cancers Screening (PDQ), health professional version. Updated 9 April 2025. www.cancer.gov/types/ovarian/hp/ovarian-screening-pdq
  9. Lange, Etzioni et al. Natural-history modelling of high-grade serous carcinoma in UKCTOCS. British Journal of Cancer. 2026. www.nature.com/articles/s41416-026-03490-2
  10. FEP Blue. Medical policy 2.04.62: multimarker serum testing related to ovarian cancer. March 2026. www.fepblue.org/-/media/PDFs/Medical-Policies/2026/March/Pharmacy-Policies/New-Policies/20462-Multimarker-Serum-Testing-Related.pdf
  11. US Food and Drug Administration. 510(k) decision summary K103358 (ROMA). www.accessdata.fda.gov/cdrh_docs/reviews/k103358.pdf
  12. National Cancer Institute. Tumor Marker Tests in Common Use. Reviewed 7 December 2023. www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/tumor-markers-list
  13. US Food and Drug Administration. List of Cleared or Approved Companion Diagnostic Devices (In Vitro and Imaging Tools). www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools
  14. Konstantinopoulos et al. Germline and somatic tumor testing in epithelial ovarian cancer: ASCO guideline. Journal of Clinical Oncology. 2020. ascopubs.org/doi/10.1200/JCO.19.02960
  15. ONS Voice. FDA fully approves mirvetuximab soravtansine-gynx for FRα-positive ovarian cancer. March 2024. www.ons.org/publications-research/voice/news-views/03-2024/fda-fully-approves-mirvetuximab-soravtansine-gynx-fr
  16. ONS Voice. FDA approves pembrolizumab with paclitaxel for platinum-resistant ovarian cancer. February 2026. www.ons.org/publications-research/voice/news-views/02-2026/fda-approves-pembrolizumab-paclitaxel-platinum
  17. Study of sialyl-Tn as a serum marker and therapeutic target in ovarian cancer. Journal of Ovarian Research. 2024. ovarianresearch.biomedcentral.com/articles/10.1186/s13048-024-01397-1
  18. Study of sialyl-Tn levels on MUC16 in endometriosis and ovarian cancer. 2012. PubMed 22367369. pubmed.ncbi.nlm.nih.gov/22367369/
  19. National Cancer Institute, Cancer Data Access System. Approved project 2025-0037: Glycovariants of CA-125 for early detection of ovarian cancer. cdas.cancer.gov/approved-projects/5526/
  20. GRAIL. Galleri test performance (page for health care professionals; company source). www.galleri.com/hcp/galleri-test-performance
  21. The ASCO Post. Annual Galleri screening reduced stage IV cancer diagnoses but missed primary endpoint in first randomized MCED trial. June 2026. ascopost.com/news/june-2026/annual-galleri-screening-reduced-stage-iv-cancer-diagnoses-but-missed-primary-endpoint-in-first-randomized-mced-trial/
  22. Targeted Oncology. FDA advisory panel review of the Galleri multi-cancer early detection test. September 2026. www.targetedonc.com/view/fda-panel-galleri-multi-cancer-early-detection-test
  23. Keck School of Medicine of USC. USC researchers develop blood test for early-stage ovarian cancer (OvaPrint). 11 October 2023. keck.usc.edu/news/usc-researchers-develop-blood-test-for-early-stage-ovarian-cancer/

About this article. Figures come from GLOBOCAN 2024, the American Cancer Society, SEER, USPSTF, the NCI PDQ summary and FDA notices; assay performance figures come from a payer policy review and several trial results from conference or trade reports, so they may change. Part of the OncoFirm™ Cancer Atlas 2026, written by the OncoFirm™ Scientific Team from the sources linked above and reflecting public information as of 1 October 2026. It is for education and is not medical advice. OncoFirm™ has no affiliation with the companies or tests named. OncoFirm™ assays are in development, have not been cleared or approved by the FDA and are not available for sale.

Collaborate on the next edition

Clinicians, laboratories, researchers and industry partners can contribute data, corrections or validation studies. Collaboration inquiry · Investor inquiry

[email protected]+1 516.900.2606Port Washington, NY